PURPOSE: This study aims to elucidate the molecular mechanism of the protective effect of PAE on the DC and the interaction between DC pathogenesis.
METHODS: Network pharmacology and molecular docking were used to identify PARP1 as a core target for PAE in DC. Animal experiments involved intervening DC mice with PAE and assessing cardiac function, oxidative stress, and apoptosis. In vitro, high glucose-induced H9c2 cells were used to validate PAE's effects on cell viability and protein expression.
RESULTS: The results showed that PAE improved the general condition of DC mice, reduced cardiac injury and cardiac insufficiency, decreased myocardial mitochondrial damage, and reduced apoptosis. In addition, PAE upregulated the expression of Bcl-2, downregulated Bax protein expression, inhibited Caspase-3 activity, and inhibited the expression of PARP1, TRPM2, CaN, and CaMKII proteins in DC mice and high glucose-induced H9c2 cells.
CONCLUSION: Mechanically, this study clarified that PAE's inhibition of the PARP1-TRPM2-CaMKII/CaN pathway reduces calcium-activated mitochondrial damage, apoptosis, and oxidative stress in diabetic cardiomyopathy. This discovery provides an innovative therapeutic strategy for DC and an experimental foundation for PAE's drug development, with significant practical implications.
METHODS AND PROCEDURES: Male Sprague-Dawley rats were divided into two normal and four obese groups. Obese prediabetes was induced by feeding a high-fat diet and sucrose water (HFSD) for 10 weeks; normal rats were given a standard diet and plain water. For the next 6 weeks, rats were grouped into the normal group (NR), which continued on the standard diet; the normal group was switched to TRF with the standard diet (NR + TRFSD); the prediabetes group (OR) was continued on HFSD; the prediabetes group was switched to TRF of HFSD (OR + TRFHFSD); the prediabetes group was switched to TRF of the standard diet (OR + TRFSD); and the prediabetes group was switched to the standard diet (OR + SD). Rats were then sacrificed, and aortic tissues were isolated and quantified for oxidative stress markers malondialdehyde, antioxidant enzyme superoxide dismutase, and inflammation markers tumor necrosis factor-α, and interleukin 1. Fasting blood glucose (FBG), body weight, Lee's index, serum insulin level, and resistance (Homeostatic Model Assessment of Insulin Resistance) were also measured.
RESULTS: Mean FBG and body weight in obese groups were higher compared to the normal groups after 10 weeks of HFDSD. Both obese-prediabetes groups that underwent TRF had reduced levels of tumor necrosis factor-α, interleukin 1, body weight, Lee's index, FBG, and insulin resistance. Furthermore, obese prediabetes on TRF with SD also reduced levels of lipid peroxidation (malondialdehyde), insulin levels and increased levels of the antioxidant enzyme (superoxide dismutase).
CONCLUSION: TRF reduced weight, improved glycaemic indices, vascular oxidative stress, and inflammation in obese-prediabetic rats.
METHODS: In this study we used the docking, molecular dynamics simulation and binding free energy approaches to identify the potent inhibitor of NLRP3 by screening the African phytocompounds and traditional Chinese medicine databases.
RESULTS: Our virtual drug screening analysis identified two lead compounds from each database, characterized by high docking scores such as SA-21676268 (-8.135 kcal/mol), SA-167673 (-10.251 kcal/mol), EA-45360194 (-10.376 kcal/mol), EA-46881231 (-10.011 kcal/mol), NEA-44258150 (-9.856 kcal/mol), NEA-135926572 (-7.662 kcal/mol), NA-163089376 (-9.237 kcal/mol), NA-440735 (-8.826 kcal/mol), TCM-392442 (-10.438 kcal/mol), and TCM-10043097 (-9.046 kcal/mol) which highlighted the strong binding affinity as compared to the control NP3-146 drug (-5.09 kcal/mol). Moreover, the values of dissociation constant further validated the strong binding affinity between the identified lead compounds and NLRP3. The dynamic stability and strong bonding energies of the lead compounds-NLRP3 complexes were confirmed by the molecular dynamic simulation and binding free energy calculation. The analysis of ADMET properties for all compounds indicated high intestinal absorption, water solubility, absence of hepatotoxicity, and skin sensitivity.
CONCLUSION: In conclusion, our molecular simulations and binding free energy calculations confirmed the strong affinity of these lead compounds for NLRP3 as compared to the control drug, highlighting their potential as part of a combinatorial therapeutic strategy for HS to effectively reduce disease-related inflammation.
METHODS: By using cross-sectional pooled data of community dwellers aged 20 years or older in eight cohorts from Taiwan, Japan and Malaysia, normative values for muscle health metrics (calf circumference (cm), relative appendicular skeletal muscle (RASM) (kilogram per square metre), body mass index (BMI)-adjusted appendicular skeletal muscle mass (kilogram/(kilogram per square metre)), handgrip strength (kilogram), five-time chair stand (seconds) and gait speed (metre per second)) in men and women, categorized by age groups, are calculated. The mean values, along with the 5th, 25th, 50th, 75th and 95th percentiles of these muscle health metrics, are also delineated for both sexes.
RESULTS: Among 34 265 (16 164 men, 18 101 women) participants from eight cohorts, calf circumference declined in age groups from 60 years onward. RASM values declined from the 50s in men but were stable in women until the 80s. ASM/BMI values showed declines in older age groups for both sexes. Handgrip strength declined similarly from 40 years of age in both sexes. Five-time chair stand performance declined from the 30s. Gait speed peaked at 1.6 m/s in men in their 50s and then declined, while it declined in women in their 60s. The inflection points for decline differed by metric and sex. The 20th percentile cutoffs for individuals aged 65-69 years were as follows: calf circumference, 33.0 cm (men) and 31.5 cm (women); RASM, 7.0 kg/m2 (men) and 5.5 kg/m2 (women); ASM/BMI, 0.78 kg/(kg/m2) (men) and 0.56 kg/(kg/m2) (women); handgrip strength, 30.4 kg (men) and 18.1 kg (women); five-time chair stand, 9.4 s (men) and 10.0 s (women); and gait speed, 0.9 m/s (both). Those in the fifth percentile of all muscle health metrics faced earlier declines than their 95th percentile counterparts did, highlighting the critical roles in identifying these high-risk groups.
CONCLUSION: The pooled analysis of eight Asian cohorts clearly outlined the age-related changes in various muscle health metrics, with the inflection point of accelerated decline showing age- and sex-specific characteristics. Defining trajectories of muscle health metrics across life stages facilitates timely interventions to mitigate age-related risks and promote healthy longevity.
METHODS: A cross-sectional study with a nationwide online survey was conducted from June to November 2022 among Malaysian doctors. The survey assessed doctors' knowledge (K), practice (P), and facilitating factors (F) for EBM (collectively referred to as KPF) using the preexisting validated Evidence-Based Medicine Questionnaire (EBMQ). Higher scores indicated better knowledge, practice, and facilitating factors for EBM implementation. The KPF percentage scores were categorised into high (> 80%), moderate (60-79%), and low (
METHODS: We searched PubMed, Web of Science, Cochrane, Embase, and SPORTDiscus from database establishment to 5 February 2024 to identify randomized controlled trials (RCTs) evaluating the effects of different dietary supplements on athletic performance in soccer players. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials. A Bayesian network meta-analysis was performed using the R software and Stata 18.0. A subgroup analysis was conducted based on the competitive level of the athletes.
RESULTS: Eighty RCTs were included, with 1,425 soccer players randomly receiving 31 different dietary supplements or placebo. The network meta-analysis showed that compared with placebo, carbohydrate + protein (SMD: 2.2, very large), carbohydrate + electrolyte (SMD: 1.3, large), bovine colostrum (SMD: moderate) and caffeine (SMD: 0.29, small) were associated with a significant effect on increasing the distance covered. Kaempferia parviflora (SMD: 0.46, small) was associated with a significant effect on enhancing muscular strength. Beta-alanine (SMD: 0.83, moderate), melatonin (SMD: 0.75, moderate), caffeine (SMD: 0.37, small), and creatine (SMD: 0.33, small) were associated with a significant effect on enhancing jump height. Magnesium creatine chelate (SMD: -3.0, very large), melatonin (SMD: -1.9, large), creatine + sodium bicarbonate (SMD: -1.4, large), and arginine (SMD: -1.2, moderate) were associated with a significant effect on decreasing sprint time. Creatine + sodium bicarbonate (SMD: -2.3, very large) and caffeine (SMD: -0.38, small) were associated with a significant effect on improving agility. Sodium pyruvate (SMD: 0.50, small) was associated with a significant effect on increasing peak power. Magnesium creatine chelate (SMD: 1.3, large) and sodium pyruvate (SMD: 0.56, small) were associated with a significant effect on increasing mean power. Carbohydrate + electrolyte (SMD: -0.56, small) was associated with a significant effect on improving the rating of perceived exertion.
CONCLUSIONS: This study suggests that a range of dietary supplements, including caffeine, creatine, creatine + sodium bicarbonate, magnesium creatine chelate, carbohydrate + electrolyte, carbohydrate + protein, arginine, beta-alanine, bovine colostrum, Kaempferia parviflora, melatonin, and sodium pyruvate, can improve athletic performance in soccer players. This review provides evidence-based guidance for soccer coaches and nutritionists on using dietary supplements to enhance specific performance measures.
OBJECTIVE: This study aims to elucidate the relationships between food fussiness, fresh fruit and vegetable consumption, and anthropometric indices of children residing in Klang Valley, Malaysia.
METHODS: A cross-sectional study was conducted to recruit 179 pairs of consenting caregiver-child. Caregivers were required to report the surveyed child's sex, date of birth, and ethnicity. The six-item food fussiness subscale from the Child Eating Behavior Questionnaire (CEBQ) was used to assess food fussiness in children. In addition, caregivers were asked to report whether their child had consumed fresh fruits and vegetables over the past month and to list all those they consistently refused to consume. For anthropometric measurements, children's body weight was measured with a digital bathroom scale, and height was measured using a portable stadiometer. Height-for-age z-scores (HAZ) and BMI-for-age z-scores (BAZ) were determined using the WHO Anthro software version 3.2.2 (for children below five) or the WHO AnthroPlus software version 1.0.4 (for children above five). The relationships between the studied variables were analyzed using IBM SPSS statistics version 27.0.
RESULTS: This study revealed that one in two children (54.2%) were fussy eaters, 9.5% did not consume fresh fruits, and 32.4% did not consume fresh vegetables over the past month. The findings from path analyses indicated that food fussiness was negatively correlated with fresh fruit and vegetable consumption. However, there were no significant direct and indirect relationships between food fussiness and anthropometric indices as indicated by HAZ and BAZ of children.
CONCLUSION: The findings of this study demonstrated that food fussiness was negatively correlated with fresh fruit and vegetable consumption. Interventions can be carried out by encouraging children to consume fruits and vegetables they typically reject, such as bean vegetables, pear, papaya, and tuberous vegetables, to prevent nutrient deficiency.
OBJECTIVE: This review aims to explore and discuss the different types of biomaterials that have been applied in the treatment of ischemic stroke, shedding light on their potentials as promising therapeutics options for this debilitating condition.
METHODS: Literature search was performed to identify publications studying the potential of three biomaterials namely: nanobioparticles, hydrogels and extracellular vesicles for ischemic stroke therapy in vitro, in vivo or in clinical using four databases, namely: PubMed, ScienceDirect, Web of Science and Scopus.
RESULTS AND DISCUSSION: The major benefits obtained from the application of nanobioparticles for ischemic stroke therapy included as the nanocarrier for drug/cell delivery, cell tracking, real time imaging, promote cell proliferation, while hydrogels provided scaffold support and conferred neuroprotection to stem cells, as well as provided neurotropic effects and controlled drug release for localized treatment. Lastly the extracellular vesicles were identified as a cell-free treatment strategy in promoting angiogenesis, neuronal differentiation and neurogenesis for ischemic stroke treatment.
CONCLUSION: Biomaterial-based therapies have their own potentials and further clinical investigations are strongly recommended to translate the therapies into more conscientious evidence-based therapy for clinical application.