OBJECTIVE: Based on their biological capability, various acetogenins were studied in the present study and compared alongside ABT-737 on molecular docking.
METHODS: The docking simulation of acetogenins was performed using AutoDock Vina software.
RESULTS: Our findings have shown eleven acetogenins-BCL-XL protein complex, namely, muricin B (2), muricin F (4), muricin H (6), muricin I (7), xylomaticin (9), annomontacin (12), annonacin (14), squamocin (15), squamostatin A (16), bullatacin (20) and annoreticulin (21) exhibited strong binding affinities lower than - 10.4 kcalmol-1 as compared to ABT-373-BCL-XL complex. Six hydrogen bonds along with hydrophobic interaction were detected on the complex of BCL-XL with muricin B (2), muricin G (5), corossolone (11), and isoannonacin-10-one A (18).
CONCLUSION: These findings indicated that some acetogenins could represent a new potential BCLXL inhibitor that could mimic the BH3-only protein for the induction of apoptosis in cancer chemotherapy.
METHODS: For identification of the minimal selective domain for apoptosis, the wild-type Apoptin gene had been reconstructed by PCR to generate segmental deletions at the N' terminal and linked with nuclear localization sites (NLS1 and NLS2). All the constructs were fused with maltose-binding protein gene and individually expressed by in vitro Rapid Translation System. Standardized dose of proteins were delivered into human breast adenocarcinoma MCF-7 cells and control human liver Chang cells by cytoplasmic microinjection, and subsequently observed for selective apoptosis effect.
RESULTS: Three of the truncated Apoptin proteins with N-terminal deletions spanning amino acid 32-83 retained the cancer selective nature of wild-type Apoptin. The proteins were successfully translocated to the nucleus of MCF-7 cells initiating apoptosis, whereas non-toxic cytoplasmic retention was observed in normal Chang cells. Whilst these truncated proteins retained the tumour-specific death effector ability, the specificity for MCF-7 cells was lost in two other truncated proteins that harbor deletions at amino acid 1-31. The detection of apoptosing normal Chang cells and MCF-7 cells upon cytoplasmic microinjection of these proteins implicated a loss in Apoptin's signature targeting activity.
CONCLUSIONS: Therefore, the critical stretch spanning amino acid 1-31 at the upstream of a known hydrophobic leucine-rich stretch (LRS) was strongly suggested as one of the prerequisite region in Apoptin for cancer targeting. Identification of this selective domain provides a platform for developing small targets to facilitating carrier-mediated-transport across cellular membrane, simultaneously promoting protein delivery for selective and effective breast cancer therapy.
METHODS: A systematic review and Delphi consensus panel (consisting of eight8 international pediatric allergists and gastroenterologists) was conducted to evaluate evidence supporting growth, tolerability, and effectiveness of pHF in non-exclusively breastfed infants.
RESULTS: None of the studies reviewed identified potential harm of pHF use compared with CMP in non-exclusively breastfed infants. There was an expert consensus that pHF use is likely as safe as intact CMP formula, given studies suggesting these have comparable nutritional parameters. No high-quality studies were identified evaluating the use of pHF to prevent allergic disease in non-exclusively breastfed infants who are not at risk for allergic disease (e.g., lacking a parental history of allergy). Limited data suggest that pHF use in non-exclusively breastfed infants may be associated with improved gastric emptying, decreased colic incidence, and other common functional gastrointestinal symptoms compared with CMP. However, because the data are of insufficient quality, the findings from these studies have to be taken with caution. No studies were identified that directly compared the different types of pHF, but there was an expert consensus that growth, allergenicity, tolerability, effectiveness, and clinical role among such pHF products may differ.
CONCLUSIONS: Limited data exist evaluating routine use of pHFs in non-exclusively breastfed infants, with no contraindications identified in the systematic review. An expert consensus considers pHFs for which data were available to be as safe as CMP formula as growth is normal. The preventive effect on allergy of pHF in infants who are not at risk for allergic disease has been poorly studied. Cost of pHF versus starter formula with intact protein differs from country to country. However, further studies in larger populations are needed to clinically confirm the benefits of routine use of pHF in non-exclusively breastfed infants. These studies should also address potential consumer preference bias.
METHOD: A comprehensive literature search was conducted to identify randomised control trials (RCTs) and non-RCTs that investigated the effectiveness of WPS on amino acids, creatinine kinase and myoglobin among athletes. Risk of Bias in Non-Randomised Studies of Interventions tool (ROBINS-I) and Cochrane Risk of Bias Assessment tool were used to rule out the quality of studies. Meta-analysis was performed using a random effect model with STATA version 14.2. The weighted mean difference was used to estimate the effectiveness of WPS against other supplements.
RESULTS: A total of 333,257 research articles were identified; of these, 15 records were included to proceed with the analysis. Meta-analysis has shown that WPS has significantly overall increased the level of essential amino acids level by 624.03 nmol/L (CI = 169.27, 1078.8; I2 = 100%; p = 0.00) and branched-chain amino acids level by 458.57 nmol/L (CI = 179.96, 737.18; I2 = 100%; p = 0.00) compared to the control group (without WPS). Moreover, was observed to decrease myoglobin level by 11.74 ng/ml (CI = - 30.24, 6.76; I2 = 79.6%; p = 0.007) and creatine kinase level by 47.05 U/L (CI = - 129.47, 35.37; I2 = 98.4%; p = 0.000) compared to the control group.
CONCLUSION: The findings revealed that the clinical evidence supports the effectiveness of WPS as a positive ergogenic aid on athletes' amino acids, creatinine kinase and myoglobin.