Creatine supplementation and resistance training to preserve muscle mass and attenuate cancer progression (CREATINE-52): a protocol for a double-blind randomized controlled trial.

BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

In vitro and in vivo studies of Dragon's blood plant (D. cinnabari)-loaded electrospun chitosan/PCL nanofibers: Cytotoxicity, antibacterial, and wound healing activities.

The D. cinnabari plant was loaded into the chitosan (Chn)/polycaprolactone (PCL) nanofibers in two forms: resin (D. cinnabari) and its ethyl acetate fraction. The Chn/PCL, Chn/PCL/D. cinnabari (CPD, 1, 3, and 5 %), and Chn/PCL/ethyl acetate extract D. cinnabari (CPED, 1, 3, and 5 %) showed no toxicity against human dermal fibroblast cells. The lactate dehydrogenase assay results indicated that the toxicity of pour, coated D. cinnabari, and CPED nanofibers were lower than 10 and 15 % after 1 and 3 days, respectively. The antibacterial results showed the inhibition zone for ethyl acetate extract D. cinnabari (ED-3 %), the Chn/PCL-2, and CPED3% nanofibers was 8.1, 7.4, 4.2, 5.1 mm, 12.8, 12.4, 21.7, 17.2 mm, and 24.7, 22.9, 37.1, 30.2 mm against S. aureus, B. subtilis, E. coli, and P. aeruginosa, respectively. The antibacterial activity results showed synergistic effect between the Chn/PCL and ethyl acetate extract D. cinnabari occurred. The diameter of wounds (1.50 × 1.50 cm diameter) made on the dorsal surface of rabbits reduced to 1.50 × 0.70, 0.50 × 0.30, 1.00 × 1.00, 0.60 × 0.50, 0.20 × 0.05, and 0.00 × 0.00 cm in the presence of ordinary gauze dressing, silver sulfadiazine, ED-3 %, Chn/PCL-2, CPD3%, and CPED3%nanofibers, respectively, after 14 days.

The effects of 12 weeks resistance training and vitamin D administration on neuromuscular joint, muscle strength and power in postmenopausal women.

BACKGROUND: This study aimed to examine the effects of 12 weeks of resistance training (RT) and vitamin D (VitD) supplementation on muscle strength and C-terminal agrin fragment (CAF) and Neurotrophin-3 (NT-3) concentrations as potential biomarkers in postmenopausal women. METHODS: This was a randomized double-blind placebo-controlled study. Forty-four healthy postmenopausal women (55.84 ± 4.70 years and 29.61 ± 4.26 kg/m2) were randomly assigned into four groups: (1) Resistance training + placebo (RT + PLA), (2) Vitamin D supplementation (VitD), (3) Resistance training + vitamin D (RT + VitD), and (4) Placebo (PLA). VitD was supplemented as an oral capsule containing 50000 IU of cholecalciferol every two weeks. RT involved leg press, chest press, leg extension, leg curl, and shoulder press exercises, performed with 3-4 sets at 70-85 % of 1RM, three times a week. RESULTS: Circulating levels of CAF and NT-3 did not significantly change following the intervention period in the study groups (p > 0.05). There were significant increases in upper and lower body muscle strength and power for RT + VitD and RT + PLA ( < 0.05), but not for VitD or PLA (p > 0.05). The muscle function gains for RT + VitD and RT + PLA were higher than those for VitD and PLA but did not differ between them. CONCLUSION: 12-week of RT interventions resulted in significant increases in muscle strength and power in postmenopausal women. However, VitD supplementation did not result in any additional benefits. The positive changes in muscle function promoted by RT do not seem to be associated with changes in the neuromuscular joint via the CAF or NT-3 as potential biomarkers.

Beta-hydroxy-beta-methylbutyrate supplementation preserves fat-free mass in collegiate boxers during acute body mass loss.

Acute body mass loss before competitions in combat sports usually leads to loss in fat-free mass. Beta-hydroxy-beta-methylbutyrate (HMB) has been shown to increase skeletal muscle mass and muscle strength in various muscle wasting conditions. This study investigated the effect of HMB supplementation on body composition and sport-specific performance in well-trained boxers consuming a hypocaloric diet. Twelve male college boxers were divided into the HMB and placebo (PLA) groups using a body weight-matched single-blind parallel design. The study comprised a 6-day weight loss period (days 1-6), followed by a 3-day competition period (days 7-9). The participants in both the groups consumed 16 kcal/kg/day, including 1.6-1.7 g/kg of carbohydrates, 1.2-1.3 g/kg of protein, and 0.45-0.5 g/kg of fat during the 9-day period. The HMB group consumed 3 g/day HMB. Body composition measurement, isometric mid-thigh pull (IMTP), and a simulated boxing match were performed at baseline and on days 7, 8, and 9. Fasting blood samples were collected on the day before day 1 and on days 7, 8, and 9. Body mass was significantly decreased after the 6-day weight loss period (HMB group: baseline: 69.4 ± 11.2 kg, day 7: 67.1 ± 11.2 kg; PLA group: baseline: 68.6 ± 12.1 kg, day 7: 65.7 ± 11.5 kg, P < 0.05) while it was unchanged on the 3-day competition period in both the groups. Fat-free mass in the HMB group was maintained throughout the 9-day period (baseline: 56.7 ± 9.3 kg, day 7: 56.3 ± 8.7 kg, day 9: 55.8 ± 9.5 kg) whereas it significantly decreased on days 7 and 9 compared to the baseline in the PLA group (baseline: 55.2 ± 6.4 kg, day 7: 54.1 ± 6.6 kg, day 9: 54.0 ± 6.6 kg, P < 0.05). In the PLA group, the average and maximal heart rates in round 1 and the average heart rate in round 2 on days 8 and 9 were significantly lower than those at baseline, while these parameters were unchanged in the HMB group. The maximal force and the rate of force development in the IMTP remained unchanged among the different timepoints in both the groups. The blood biochemical parameters were similar at any timepoint between the PLA and HMB groups. HMB supplementation during acute weight loss may preserve fat-free mass and maintain heart rate response in subsequent simulated matches in well-trained boxers. In addition, HMB supplementation had a nonsignificant effect on glucose, fat, and protein metabolism during energy restriction.

Liver Extracellular Matrix-Based Nanofiber Scaffolds for the Culture of Primary Hepatocytes and Drug Screening.

Immortalized liver cell lines and primary hepatocytes are currently used as in vitro models for hepatotoxic drug screening. However, a decline in the viability and functionality of hepatocytes with time is an important limitation of these culture models. Advancements in tissue engineering techniques have allowed us to overcome this challenge by designing suitable scaffolds for maintaining viable and functional primary hepatocytes for a longer period of time in culture. In the current study, we fabricated liver-specific nanofiber scaffolds with polylactic acid (PLA) along with a decellularized liver extracellular matrix (LEM) by the electrospinning technique. The fabricated hybrid PLA-LEM scaffolds were more hydrophilic and had better swelling properties than the PLA scaffolds. The hybrid scaffolds had a pore size of 38 ± 8 µm and supported primary rat hepatocyte cultures for 10 days. Increased viability (2-fold increase in the number of live cells) and functionality (5-fold increase in albumin secretion) were observed in primary hepatocytes cultured on the PLA-LEM scaffolds as compared to those on conventional collagen-coated plates on day 10 of culture. A significant increase in CYP1A2 enzyme activity was observed in hepatocytes cultured on PLA-LEM hybrid scaffolds in comparison to those on collagen upon induction with phenobarbital. Drugs like acetaminophen and rifampicin showed the highest toxicity in hepatocytes cultured on hybrid scaffolds. Also, the lethal dose of these drugs in rodents was accurately predicted as 1.6 g/kg and 594 mg/kg, respectively, from the corresponding IC50 values obtained from drug-treated hepatocytes on hybrid scaffolds. Thus, the fabricated liver-specific electrospun scaffolds maintained primary hepatocyte viability and functionality for an extended period in culture and served as an effective ex vivo drug screening platform to predict an accurate in vivo drug-induced hepatotoxicity.

New Zealand Blackcurrant Increases Postexercise Hypotension Following Sustained Moderate-Intensity Exercise.

Previous observations demonstrate New Zealand blackcurrant (NZBC) extract to alter cardiovascular responses at rest without prior exercise. However, the prolonged effects of NZBC on blood pressure and heart rate variability following exercise are not known. Participants (n15 [five women], age: 31 ± 9 years, maximal oxygen uptake: 44 ± 9 ml·kg-1·min-1) undertook a control condition of 2 hr of lying supine rest. Subsequently, in a double-blind, placebo (PLA)-controlled, randomized crossover design participants completed 1 hr of treadmill exercise at 50% maximal oxygen uptake followed by 2-hr supine rest with blood pressure and heart rate variability measurement following a 7-day intake of NZBC and PLA. With NZBC, there was an increase in average fat oxidation (NZBC: 0.24 ± 0.11 vs. PLA: 0.17 ± 0.11 g/min, p = .005), and larger high-frequency relative power during the exercise (p = .037). In the 2-hr rest period, delta change for systolic pressure was larger with NZBC than PLA (Control vs. NZBC: -5.6 ± 6.4, Control vs. PLA: -3.5 ± 6.0 mmHg, p = .033) but was not different for diastolic or mean arterial pressure. There were no alterations in heart rate variabilities during the 2 hr following the exercise with NZBC. A 7-day intake of NZBC causes a larger postexercise hypotension response in young, physically active men and women following 1 hr of treadmill exercise at 50% maximal oxygen uptake.

Biological evaluation and osteogenic potential of polyhydroxybutyrate-keratin/Al2O3 electrospun nanocomposite scaffold: A novel bone regeneration construct.

In this study, the effect of alumina nanowire on the physical and biological properties of polyhydroxybutyrate-keratin (PHB-K) electrospun scaffold was investigated. First, PHB-K/alumina nanowire nanocomposite scaffolds were made with an optimal concentration of 3 wt% alumina nanowire by using the electrospinning method. The samples were examined in terms of morphology, porosity, tensile strength, contact angle, biodegradability, bioactivity, cell viability, ALP activity, mineralization ability, and gene expression. The nanocomposite scaffold provided a porosity of >80 % and a tensile strength of about 6.72 MPa, which were noticeable for an electrospun scaffold. AFM images showed an increase in surface roughness with the presence of alumina nanowires. This led to an improvement in the degradation rate and bioactivity of PHB-K/alumina nanowire scaffolds. The viability of mesenchymal cells, alkaline phosphatase secretion, and mineralization significantly increased with the presence of alumina nanowire compared to PHB and PHB-K scaffolds. In addition, the expression level of collagen I, osteocalcin, and RUNX2 genes in nanocomposite scaffolds increased significantly compared to other groups. In general, this nanocomposite scaffold could be a novel and interesting construct for osteogenic induction in bone tissue engineering.

Angiogenesis coupled with osteogenesis in a bone tissue engineering scaffold enhances bone repair in osteoporotic bone defects.

Increased life expectancy has resulted in an increase in osteoporosis incidence worldwide. The coupling of angiogenesis and osteogenesis is indispensable for bone repair. Although traditional Chinese medicine (TCM) exerts therapeutic effects on osteoporosis, TCM-related scaffolds, which focus on the coupling of angiogenesis and osteogenesis, have not yet been used for the treatment of osteoporotic bone defects.Panax notoginsengsaponin (PNS), the active ingredient ofPanax notoginseng, was added to a poly (L-lactic acid) (PLLA) matrix. Osteopractic total flavone (OTF), the active ingredient ofRhizoma Drynariae, was encapsulated in nano-hydroxyapatite/collagen (nHAC) and added to the PLLA matrix. Magnesium (Mg) particles were added to the PLLA matrix to overcome the bioinert character of PLLA and neutralize the acidic byproducts generated by PLLA. In this OTF-PNS/nHAC/Mg/PLLA scaffold, PNS was released faster than OTF. The control group had an empty bone tunnel; scaffolds containing OTF:PNS = 100:0, 50:50, and 0:100 were used as the treatment groups. Scaffold groups promoted new vessel and bone formation, increased the osteoid tissue, and suppressed the osteoclast activity around osteoporotic bone defects. Scaffold groups upregulated the expression levels of angiogenic and osteogenic proteins. Among these scaffolds, the OTF-PNS (50:50) scaffold exhibited a better capacity for osteogenesis than the OTF-PNS (100:0 and 0:100) scaffolds. Activation of the bone morphogenic protein (BMP)-2/BMP receptor (BMPR)-1A/runt-related transcription factor (RUNX)-2signaling pathway may be a possible mechanism for the promotion of osteogenesis. Our study demonstrated that the OTF-PNS/nHAC/Mg/PLLA scaffold could promote osteogenesis via the coupling of angiogenesis and osteogenesis in osteoporotic rats with bone defects, and activating theBMP-2/BMPR1A/RUNX2signaling pathway may be an osteogenesis-related mechanism. However, further experiments are necessary to facilitate its practical application in the treatment of osteoporotic bone defects.

Fish oil supplementation fails to modulate indices of muscle damage and muscle repair during acute recovery from eccentric exercise in trained young males.

We aimed to investigate the influence of 4-wk of fish oil (FO) supplementation on markers of muscle damage, inflammation, muscle soreness, and muscle function during acute recovery from eccentric exercise in moderately trained males. Sixteen moderately-trained males ingested 5 g/d of FO (n = 8) or soybean oil (placebo) capsules (n = 8) for 4-wk prior to- and 3-d following an acute eccentric exercise bout. Eccentric exercise consisted of 12 sets of isokinetic knee extension and knee flexion. Indices of muscle damage, soreness, function and inflammation were measured at baseline and during exercise recovery. Eccentric exercise elicited an increase in muscle soreness (p < 0.010) and thigh volume (p < 0.001), and reduced peak isometric torque by 31.7 ± 6.9%, (p < 0.05, 95% CI 10.6-52.8) during 3-d of recovery. Blood omega-3 polyunsaturated fatty acid concentration was 14.9 ± 2.4% higher in FO than PLA (p < 0.01, 95% CI 9.8-20.1). However, FO did not ameliorate the cumulative creatine kinase response (expressed as AUC; p = 0.368), inflammation (p = 0.400), muscle soreness (p > 0.140), or muscle function (p > 0.249) following eccentric exercise. FO supplementation confers no clear benefit in terms of ameliorating the degree of muscle damage, or facilitating the muscle repair process, during acute eccentric exercise recovery. These data suggest that FO supplementation does not provide an effective nutritional strategy to promote exercise recovery, at least in moderately-trained young men.Abbreviations: ANOVA: Analysis of variance; AUC: Area under curve; CI: Confidence interval; CK: Creatine kinase; CMJ: Countermovement jump; COX: Cyclooxygenase; CRP: C-reactive protein; DHA: Docosahexaenoic acid; DOMS: Delayed-onset muscle soreness; EIMD: Exercise-induced muscle damage; En%: Energy percent; EPA: Eicosapentaenoic acid; FO: Fish oil; IL-6: Interleukin-6; LDH: Lactate dehydrogenase; LOX: Lipoxygenase; Mb: Myoglobin; mTOR: Mechanistic target of rapamycin; PLA: Placebo; ROM: Range of motion; ROS: Reactive oxygen species; SD: Standard deviation; SEM: Standard error of the mean; TNF-α: Tumour necrosis factor alpha; VAS: Visual analogue scale; Ω3-PUFA: Omega-3 polyunsaturated fatty acids; Ω6-PUFA: Omega-6 polyunsaturated fatty acidsHighlightsThe anti-inflammatory properties of omega-3 polyunsaturated fatty acids, alongside their propensity to incorporate into the muscle phospholipid membrane underpins the idea that fish oil supplementation may attenuate muscle damage and promote muscle repair following eccentric-based exercise.Four weeks of high-dose (5 g/d) fish oil supplementation prior to eccentric exercise failed to attenuate the rise in creatine kinase concentration and muscle soreness during acute exercise recovery in physically-active young men.Future studies are warranted to investigate the efficacy of combining omega-3 polyunsaturated fatty acids with other nutrients (i.e. protein/amino acids) for the promotion of muscle recovery following eccentric-based damaging exercise.

Bone turnover following high-impact exercise is not modulated by collagen supplementation in young men: A randomized cross-over trial.

INTRODUCTION: We assessed whether collagen supplementation augments the effects of high-impact exercise on bone turnover and whether a higher exercise frequency results in a greater benefit for bone metabolism. METHODS: In this randomized, cross-over trial, 14 healthy males (age 24 ± 4 y, BMI 22.0 ± 2.1 kg/m2) performed 5-min of high-impact exercise once (JUMP+PLA and JUMP+COL) or twice daily (JUMP2+COL2) during a 3-day intervention period, separated by a 10-day wash out period. One hour before every exercise bout participants ingested 20 g hydrolysed collagen (JUMP+COL and JUMP2+COL2) or a placebo control (JUMP+PLA). Blood markers of bone formation (P1NP) and resorption (CTXI) were assessed in the fasted state before the ingestion of the initial test drinks and 24, 48, and 72 h thereafter. In JUMP+PLA and JUMP+COL, additional blood samples were collected in the postprandial state at 1, 2, 3, 4, 5 and 13 h after ingestion of the test drink. RESULTS: In the postprandial state, serum P1NP concentrations decreased marginally from 99 ± 37 to 93 ± 33 ng/mL in JUMP+COL, and from 97 ± 32 to 92 ± 31 ng/mL in JUMP+PLA, with P1NP levels having returned to baseline levels after 13 h (time-effect, P = 0.053). No differences in serum P1NP concentrations were observed between JUMP+PLA and JUMP+COL (time x treatment, P = 0.58). Serum CTX-I concentrations showed a ~ 50 % decline (time, P < 0.001) in the postprandial state in JUMP+COL (0.9 ± 0.3 to 0.4 ± 0.2 ng/mL) and JUMP+PLA (0.9 ± 0.3 to 0.4 ± 0.2 ng/mL), with no differences between treatments (time x treatment, P = 0.17). Fasted serum P1NP concentrations increased ~8 % by daily jumping exercise (time-effect, P < 0.01), with no differences between treatments (time x treatment, P = 0.71). Fasted serum CTX-I concentrations did not change over time (time-effect, P = 0.41) and did not differ between treatments (time x treatment, P = 0.58). CONCLUSIONS: Five minutes of high-impact exercise performed daily stimulates bone formation during a 3-day intervention period. This was indicated by an increase in fasted serum P1NP concentrations, rather than an acute increase in post-exercise serum P1NP concentrations. Collagen supplementation or an increase in exercise frequency does not further increase serum P1NP concentrations. The bone resorption marker CTX-I was not affected by daily short-duration high-impact exercise with or without concurrent collagen supplementation.

Resistance Exercise Training Increases Muscle Mass and Strength in Prostate Cancer Patients on Androgen Deprivation Therapy.

PURPOSE: This study aimed to assess the effects of 20 wk resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance, and aerobic capacity in prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS: Sixty prostate cancer patients receiving ADT were randomly assigned to perform 20 wk of resistance exercise training with supplementation of 31 g whey protein (EX + PRO, n = 30) or placebo (EX + PLA, n = 30), consumed immediately after exercise and every night before sleep. A separate control group (CON, n = 36) only received usual care. At baseline and after 20 wk, body composition (dual-energy x-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-Second Chair Stand Test, and Stair Climb Test), aerobic capacity (cardiopulmonary exercise test), and habitual dietary intake (food diary) were assessed. Data were analyzed using a two-factor repeated-measures ANOVA. RESULTS: Over time, muscle mass and strength increased in EX + PRO and EX + PLA and decreased in CON. Total fat mass and fat percentage increased in EX + PRO and CON, but not in EX + PLA. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in EX + PLA, but it decreased in EX + PRO and CON. Habitual protein intake (without supplements) averaged >1.0 g·kg body weight -1 ·d -1 , with no differences over time or between groups. CONCLUSIONS: In prostate cancer patients, resistance exercise training counteracts the adverse effects of ADT on body composition, muscle mass, muscle strength, and aerobic capacity, with no additional benefits of protein supplementation.

Nanosilica-Anchored Polycaprolactone/Chitosan Nanofibrous Bioscaffold to Boost Osteogenesis for Bone Tissue Engineering.

The strategy of incorporating bioactive inorganic nanomaterials without side effects as osteoinductive supplements is promising for bone regeneration. In this work, a novel biomass nanofibrous scaffold synthesized by electrospinning silica (SiO2) nanoparticles into polycaprolactone/chitosan (PCL/CS) nanofibers was reported for bone tissue engineering. The nanosilica-anchored PCL/CS nanofibrous bioscaffold (PCL/CS/SiO2) exhibited an interlinked continuous fibers framework with SiO2 nanoparticles embedded in the fibers. Compact bone-derived cells (CBDCs), the stem cells derived from the bone cortex of the mouse, were seeded to the nanofibrous bioscaffolds. Scanning electron microscopy and cell counting were used to observe the cell adhesion. The Counting Kit-8 (CCK-8) assay was used. Alkaline phosphatase (ALP), Alizarin red staining, real-time Polymerase Chain Reaction and Western blot tests were performed to confirm the osteogenesis of the CBDCs on the bioscaffolds. The research results demonstrated that the mechanical property of the PCL together with the antibacterial and hydrophilic properties of the CS are conducive to promoting cell adhesion, growth, migration, proliferation and differentiation. SiO2 nanoparticles, serving as bone induction factors, effectively promote the osteoblast differentiation and bone regeneration. This novel SiO2-anchored nanofibrous bioscaffold with superior bone induction activity provides a better way for bone tissue regeneration.

High Doses of Caffeine Increase Muscle Strength and Calcium Release in the Plasma of Recreationally Trained Men.

The effects of acute caffeine supplementation on muscular strength remain unclear. We examined the effects of two different doses of caffeine on muscle strength and calcium in plasma compared to placebo using a crossover, randomized, double-blind, placebo-controlled design. Twenty-one (n = 21) recreationally resistance-trained participants were randomly assigned into three experimental conditions: 6 mg·kg bw−1 of caffeine (CF6); 8 mg·kg bw−1 of caffeine (CF8); or placebo (PLA), with a 7-day washout period between conditions. Muscular strength assessments were made for both upper (bench press) and lower body muscles (squat and deadlift). Calcium release in plasma was measured on five different occasions. Bench press (CF8: 100.1 ± 1.9 kg; PLA: 94.2 ± 2.5 kg), deadlift (CF8: 132.8 ± 3.5 kg; PLA: 120.7 ± 5.7 kg), and squat (CF8: 130.1 ± 4.9 kg; PLA 119.4 ± 5.4 kg) strength were all significantly (p < 0.001) improved in CF8 compared to PLA. Calcium release in plasma was significantly increased in CF8, whereas no changes were observed in CF6 or PLA. Overall, 8 mg·kg bw−1 of caffeine appears to be an effective dose to optimize upper and lower body muscular strength and calcium release in recreationally trained participants.

Effects of caffeine, methylliberine, and theacrine on vigilance, marksmanship, and hemodynamic responses in tactical personnel: a double-blind, randomized, placebo-controlled trial.

Background: Tactical athletes require fast reaction times (RT) along with high levels of vigilance and marksmanship performance. Caffeine has been shown to improve these measures but also results in increased blood pressure and jitteriness. Research on other purine alkaloids, such as methylliberine and theacrine, has suggested they do not increase blood pressure or jitteriness to the same extent, but their impact on tactical performance is unknown. Methods: A between-subjects, randomized, placebo-controlled design was used to test the effects of placebo (PLA), 300 mg caffeine (CAF), and a combination of 150 mg caffeine, 100 mg methylliberine, and 50 mg theacrine (CMT) on RT and marksmanship along with hemodynamic and arousal measures following a sustained vigilance task in tactical personnel (n = 48). Following consumption of the supplement, participants underwent a 150-min protocol consisting of two rounds. Each round began with leisurely reading followed by a 30-min vigilance task before beginning two trials of movement and marksmanship tasks. Hemodynamics and felt arousal were assessed throughout the protocol. Composite Z-scores were calculated for overall performance measures at each timepoint, and mixed-effects models were used to assess differences in RT, accuracy, and composite Z-scores along with hemodynamics and felt arousal. An α-level of 0.05 was used to determine statistical significance, and Cohen's d was used to quantify effect sizes. Results: A Group-by-Time interaction for vigilance RT (P = 0.038) indicated improvements for both CAF and CMT from round 1 to round 2 (P < 0.01) while PLA did not change (P = 0.27). No Group main effects or Group-by-Time interactions were found for movement or marksmanship performance (P > 0.20). Group main effects for systolic (SBP; P = 0.001) and diastolic blood pressure (DBP; P = 0.028) indicated higher SBP in CAF (P = 0.003, d= 0.84) and CMT (P = 0.007, d= 0.79) compared to PLA but only higher DBP in CAF (P = 0.025, d= 0.74). No Group-by-Time interaction or Group main effect was found for felt arousal (P > 0.16). Conclusions: These findings suggest similar benefits on RT during a vigilance task between CAF, containing 300 mg caffeine, and CMT above PLA, though CAF resulted in slightly less favorable hemodynamic changes. This study is the first to provide data showing similar efficacy of combined caffeine, methylliberine, and theacrine compared to double the caffeine dose consumed alone on vigilance RT but without a significant rise in DBP above PLA in tactical personnel.

Royal jelly plus coenzyme Q10 supplementation improves high-intensity interval exercise performance via changes in plasmatic and salivary biomarkers of oxidative stress and muscle damage in swimmers: a randomized, double-blind, placebo-controlled pilot trial.

Background: Excessive production of free radicals caused by many types of exercise results in oxidative stress, which leads to muscle damage, fatigue, and impaired performance. Supplementation with royal jelly (RJ) or coenzyme Q10 (CoQ10) has been shown to attenuate exercise-induced oxidant stress in damaged muscle and improve various aspects of exercise performance in many but not all studies. Nevertheless, the effects of treatments based on RJ plus CoQ10 supplementation, which may be potentially beneficial for reducing oxidative stress and enhancing athletic performance, remain unexplored. This study aimed to examine whether oral RJ and CoQ10 co-supplementation could improve high-intensity interval exercise (HIIE) performance in swimmers, inhibiting exercise-induced oxidative stress and muscle damage. Methods: Twenty high-level swimmers were randomly allocated to receive either 400 mg of RJ and 60 mg of CoQ10 (RJQ) or matching placebo (PLA) once daily for 10 days. Exercise performance was evaluated at baseline, and then reassessed at day 10 of intervention, using a HIIE protocol. Diene conjugates (DC), Schiff bases (SB), and creatine kinase (CK) were also measured in blood plasma and saliva before and immediately after HIIE in both groups. Results: HIIE performance expressed as number of points according to a single assessment system developed and approved by the International Swimming Federation (FINA points) significantly improved in RJQ group (p = 0.013) compared to PLA group. Exercise-induced increase in DC, SB, and CK levels in plasma and saliva significantly diminished only in RJQ group (p < 0.05). Regression analysis showed that oral RJQ administration for 10 days was significantly associated with reductions in HIIE-induced increases in plasmatic and salivary DC, SB, and CK levels compared to PLA. Principal component analysis revealed that swimmers treated with RJQ are grouped by both plasmatic and salivary principal components (PC) into a separate cluster compared to PLA. Strong negative correlation between the number of FINA points and plasmatic and salivary PC1 values was observed in both intervention groups. Conclusion: The improvements in swimmers' HIIE performance were due in significant part to RJQ-induced reducing in lipid peroxidation and muscle damage in response to exercise. These findings suggest that RJQ supplementation for 10 days is potentially effective for enhancing HIIE performance and alleviating oxidant stress. Abbreviations: RJ, royal jelly; CoQ10, coenzyme Q10; HIIE, high-intensity interval exercise; DC, diene conjugates; SB, Schiff bases; CK, creatine kinase; RJQ, royal jelly plus coenzyme Q10; PLA, placebo; FINA points, points according to a single assessment system developed and approved by the International Swimming Federation; ROS, reactive oxygen species; 10H2DA, 10-hydroxy-2-decenoic acid; AMPK, 5'-AMP-activated protein kinase; FoxO3, forkhead box O3; MnSOD, manganese-superoxide dismutase; CAT, catalase; E, optical densities; PCA, principal component analysis; PC, principal component; MCFAs, medium-chain fatty acids; CaMKKß, Ca2+/calmodulin-dependent protein kinase ß; TBARS, thiobarbituric acid reactive substances; MDA, malondialdehyde.

Pre-sleep protein supplementation after an acute bout of evening resistance exercise does not improve next day performance or recovery in resistance trained men.

Background: To evaluate the effect of pre-sleep protein supplementation after an acute bout of evening resistance training on next day performance and recovery the following day in physically active men. Methods: Eighteen resistance trained men performed a single bout of resistance exercise then received either a pre-sleep protein (PRO) supplement containing 40 g of casein protein (PRO; n = 10; mean ± SD; age = 24 ± 4 yrs; height = 1.81 ± 0.08 m; weight = 84.9 ± 9.5 kg) or a non-caloric, flavor matched placebo (PLA; n = 8; age = 28 ± 10 yrs; height = 1.81 ± 0.07 m; weight = 86.7 ± 11.0 kg) 30 min before sleep (1 h after a standard recovery drink). Blood samples were obtained pre-exercise and the following morning (+12-h) to measure creatine kinase and C-reactive protein. Visual analog scales were utilized to assess perceived pain, hunger, and recovery. One-repetition maximum (1RM) tests for barbell bench press and squat were performed pre-exercise and the following morning (+12-h). Statistical analysis was performed using SPSS (V.23) and p ≤ 0.05 was considered statistically significant. Results: There were no significant differences between the groups in next morning performance or muscle damage biomarkers. However, pre-sleep PRO resulted in a lower perception of hunger that approached significance the following morning when compared to PLA (PRO:43.6 ± 31.2, PLA: 69.4 ± 2.22; 95% C.I. = -53.6, 2.0; p = 0.07; d = 0.95). Conclusions: Following an evening bout of exercise, pre-sleep PRO did not further improve next morning muscle damage biomarkers or maximal strength performance in resistance trained men compared to a non-caloric PLA. However, there may be implications for lower perceived hunger the next morning with pre-sleep PRO consumption compared to PLA.

Acute Effects of Beetroot Juice Supplements on Lower-Body Strength in Female Athletes: Double-Blind Crossover Randomized Trial.

BACKGROUND: Beetroot juice (BRJ) is used as an ergogenic aid, but no previous study has analyzed the effect this supplement has on the production of explosive force and muscular endurance in physically active women. HYPOTHESIS: BRJ improves explosive force and muscular endurance in the lower limbs of physically active women. STUDY DESIGN: Randomized double-blind crossover study. LEVEL OF EVIDENCE: Level 3. METHODS: Fourteen physically active women performed a countermovement jump (CMJ) test, a back squat test for assessing velocity and power at 50% and 75% of one-repetition maximum (1RM), and the number of repetitions on a muscular endurance test consisting of 3 sets at 75% of 1RM in a resistance training protocol comprising 3 exercises (back squat, leg press, and leg extension). The participants performed the test in 2 sessions, 150 minutes after ingesting 70 mL of either BRJ (400 mg of nitrate) or a placebo (PLA). RESULTS: A greater maximum height was achieved in the CMJ after consuming BRJ compared with a PLA (P = 0.04; effect size (ES) = 0.34). After a BRJ supplement at 50% 1RM, a higher mean velocity [+6.7%; P = 0.03; (ES) = 0.39 (-0.40 to 1.17)], peak velocity (+6%; P = 0.04; ES = 0.39 [-0.40 to 1.17]), mean power (+7.3%; P = 0.02; ES = 0.30 [-0.48 to 1.08]) and peak power (+6%; P = 0.04; ES = 0.20 [-0.59 to 0.98]) were attained in the back squat test. In the muscular endurance test, BRJ increased performance compared with the PLA (P < 0.00; ηp2 = 0.651). CONCLUSION: BRJ supplements exert an ergogenic effect on the ability to produce explosive force and muscular endurance in the lower limbs in physically active women. CLINICAL RELEVANCE: If physically active women took a BRJ supplement 120 minutes before resistance training their performance could be enhanced.

Biodegradable Nanoparticles Loaded with Levodopa and Curcumin for Treatment of Parkinson's Disease.

Background: Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. Levodopa (L-DOPA) remains the gold-standard drug available for treating PD. Curcumin has many pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anti-amyloid, and antitumor properties. Copolymers composed of Poly (ethylene oxide) (PEO) and biodegradable polyesters such as Poly (ε-caprolactone) (PCL) can self-assemble into nanoparticles (NPs). This study describes the development of NH2-PEO-PCL diblock copolymer positively charged and modified by adding glutathione (GSH) on the outer surface, resulting in a synergistic delivery of L-DOPA curcumin that would be able to pass the blood-brain barrier. Methods: The NH2-PEO-PCL NPs suspensions were prepared by using a nanoprecipitation and solvent displacement method and coated with GSH. NPs were submitted to characterization assays. In order to ensure the bioavailability, Vero and PC12 cells were treated with various concentrations of the loaded and unloaded NPs to observe cytotoxicity. Results: NPs have successfully loaded L-DOPA and curcumin and were stable after freeze-drying, indicating advancing into in vitro toxicity testing. Vero and PC12 cells that were treated up to 72 h with various concentrations of L-DOPA and curcumin-loaded NP maintained high viability percentage, indicating that the NPs are biocompatible. Conclusions: NPs consisting of NH2-PEO-PCL were characterized as potential formulations for brain delivery of L-DOPA and curcumin. The results also indicate that the developed biodegradable nanomicelles that were blood compatible presented low cytotoxicity.

Antiviral Characterization of Advanced Materials: Use of Bacteriophage Phi 6 as Surrogate of Enveloped Viruses Such as SARS-CoV-2.

The bacteriophage phi 6 is a virus that belongs to a different Baltimore group than SARS-CoV-2 (group III instead of IV). However, it has a round-like shape and a lipid envelope like SARS-CoV-2, which render it very useful to be used as a surrogate of this infectious pathogen for biosafety reasons. Thus, recent antiviral studies have demonstrated that antiviral materials such as calcium alginate hydrogels, polyester-based fabrics coated with benzalkonium chloride (BAK), polyethylene terephthalate (PET) coated with BAK and polyester-based fabrics coated with cranberry extracts or solidified hand soap produce similar log reductions in viral titers of both types of enveloped viruses after similar viral contact times. Therefore, researchers with no access to biosafety level 3 facilities can perform antiviral tests of a broad range of biomaterials, composites, nanomaterials, nanocomposites, coatings and compounds against the bacteriophage phi 6 as a biosafe viral model of SARS-CoV-2. In fact, this bacteriophage has been used as a surrogate of SARS-CoV-2 to test a broad range of antiviral materials and compounds of different chemical natures (polymers, metals, alloys, ceramics, composites, etc.) and forms (films, coatings, nanomaterials, extracts, porous supports produced by additive manufacturing, etc.) during the current pandemic. Furthermore, this biosafe viral model has also been used as a surrogate of SARS-CoV-2 and other highly pathogenic enveloped viruses such as Ebola and influenza in a wide range of biotechnological applications.

Effect of nitrate supplementation on skeletal muscle motor unit activity during isometric blood flow restriction exercise.

BACKGROUND: Nitrate (NO3-) supplementation has been reported to lower motor unit (MU) firing rate (MUFR) during dynamic resistance exercise; however, its impact on MU activity during isometric and ischemic exercise is unknown. PURPOSE: To assess the effect of NO3- supplementation on knee extensor MU activities during brief isometric contractions and a 3 min sustained contraction with blood flow restriction (BFR). METHODS: Sixteen healthy active young adults (six females) completed two trials in a randomized, double-blind, crossover design. Trials were preceded by 5 days of either NO3- (NIT) or placebo (PLA) supplementation. Intramuscular electromyography was used to determine the M. vastus lateralis MU potential (MUP) size, MUFR and near fibre (NF) jiggle (a measure of neuromuscular stability) during brief (20 s) isometric contractions at 25% maximal strength and throughout a 3 min sustained BFR isometric contraction. RESULTS: Plasma nitrite (NO2-) concentration was elevated after NIT compared to PLA (475 ± 93 vs. 198 ± 46 nmol L-1, p < 0.001). While changes in MUP area, NF jiggle and MUFR were similar between NIT and PLA trials (all p > 0.05), MUP duration was shorter with NIT compared to PLA during brief isometric contractions and the sustained ischemic contraction (p < 0.01). In addition, mean MUP duration, MUP area and NF jiggle increased, and MUFR decreased over the 3 min sustained BFR isometric contraction for both conditions (all p < 0.05). CONCLUSIONS: These findings provide insight into the effect of NO3- supplementation on MUP properties and reveal faster MUP duration after short-term NO3- supplementation which may have positive implications for skeletal muscle contractile performance.