Comparative Efficacy of Different Protein Supplements on Muscle Mass, Strength, and Physical Indices of Sarcopenia among Community-Dwelling, Hospitalized or Institutionalized Older Adults Undergoing Resistance Training: A Network Meta-Analysis of Randomized Controlled Trials.

Aging-related sarcopenia exerts harmful impacts on muscle mass, strength, and physical mobility. Protein supplementation has been demonstrated to augment efficacy of resistance training (RT) in elderly. This study compared the relative effects of different protein supplements on muscle mass, strength, and mobility outcomes in middle-aged and older individuals undergoing RT. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) examining the efficacy of protein supplement plus RT in untrained community-dwelling adults, hospitalized, or institutionalized residents who suffered acute or chronic health conditions. Network meta-analysis (NMA) was performed using a frequentist method for all analyses. Treatment effects for main outcomes were expressed as standard mean difference (SMD) with 95% confidence interval (CI). We used the surface-under-the cumulative-ranking (SUCRA) scores to rank probabilities of effect estimation among all identified treatments. Meta-regression analyses were performed to identify any relevant moderator of the treatment efficacy and results were expressed as ß with 95% credible interval (CrI). We finally included 78 RCTs (5272 participants) for analyses. Among the six protein sources identified in this NMA, namely whey, milk, casein, meat, soy, and peanut, whey supplement yielded the most effective treatments augmenting efficacy of RT on muscle mass (SMD = 1.29, 95% CI: 0.96, 1.62; SUCRA = 0.86), handgrip strength (SMD = 1.46, 95% CI: 0.92, 2.00; SUCRA = 0.85), and walking speed (SMD = 0.73, 95% CI: 0.39, 1.07; SUCRA = 0.84). Participant's health condition, sex, and supplementation dose were significant factors moderating the treatment efficacy on muscle mass (ß = 0.74; 95% CrI: 0.22, 1.25), handgrip strength (ß = -1.72; 95% CrI: -2.68, -0.77), and leg strength (ß = 0.76; 95% CrI: 0.06, 1.47), respectively. Our findings suggest whey protein yields the optimal supplements to counter sarcopenia in older individuals undergoing RT.

Comparative Efficacy of Intra-Articular Injection, Physical Therapy, and Combined Treatments on Pain, Function, and Sarcopenia Indices in Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials.

Knee osteoarthritis (KOA) is associated with a high risk of sarcopenia. Both intra-articular injections (IAIs) and physical therapy (PT) exert benefits in KOA. This network meta-analysis (NMA) study aimed to identify comparative efficacy among the combined treatments (IAI+PT) in patients with KOA. Seven electronic databases were systematically searched from inception until January 2023 for randomized controlled trials (RCTs) reporting the effects of IAI+PT vs. IAI or PT alone in patients with KOA. All RCTs which had treatment arms of IAI agents (autologous conditioned serum, botulinum neurotoxin type A, corticosteroids, dextrose prolotherapy (DxTP), hyaluronic acid, mesenchymal stem cells (MSC), ozone, platelet-rich plasma, plasma rich in growth factor, and stromal vascular fraction of adipose tissue) in combination with PT (exercise therapy, physical agent modalities (electrotherapy, shockwave therapy, thermal therapy), and physical activity training) were included in this NMA. A control arm receiving placebo IAI or usual care, without any other IAI or PT, was used as the reference group. The selected RCTs were analyzed through a frequentist method of NMA. The main outcomes included pain, global function (GF), and walking capability (WC). Meta-regression analyses were performed to explore potential moderators of the treatment efficacy. We included 80 RCTs (6934 patients) for analyses. Among the ten identified IAI+PT regimens, DxTP plus PT was the most optimal treatment for pain reduction (standard mean difference (SMD) = -2.54) and global function restoration (SMD = 2.28), whereas MSC plus PT was the most effective for enhancing WC recovery (SMD = 2.54). More severe KOA was associated with greater changes in pain (ß = -2.52) and WC (ß = 2.16) scores. Combined IAI+PT treatments afford more benefits than do their corresponding monotherapies in patients with KOA; however, treatment efficacy is moderated by disease severity.

Fibroblast Activation Protein α Activated Tripeptide Bufadienolide Antitumor Prodrug with Reduced Cardiotoxicity.

Bufadienolides are the major pharmacologic constituents of traditional Chinese medicine Chan'su, which is frequently used clinically for cancer treatment in China. Motivated by reducing or avoiding the cardiac toxicity of bufadienolides, we have designed, synthesized, and evaluated the fibroblast activation protein α (FAPα) activated tripeptide arenobufagin prodrugs with the purpose of improving the safety of arenobufagin (a representative bufadienolide). Among these FAPα-activated prodrugs, 3f exhibited the best hydrolytic efficiency by recombinant human FAPα (rhFAPα) and was activated in tumors. The LD50 of 3f was 6.5-fold higher than that of arenobufagin. We also observed that there are nonapparent changes in echocardiography, pathological section of cardiac muscle, and the lactate dehydrogenase activities (LDH) in 3f-treatment tumor-bearing mice, even when the dose reached 3 times the amount of parent drug arenobufagin that was used. Compound 3f also exhibits significant antitumor activity in vitro and in vivo. The improved safety profile and favorable anticancer properties of 3f warrant further studies of the potential clinical implications. Our study suggests that FAPα prodrug strategy is an effective approach for successful increasing the therapeutic window of bufadienolides.