Here we compare the efficacy of anti-obesity drugs alone or combined with exercise training on body weight and exercise capacity of obese patients.Randomized clinical trials that assessed the impact of any anti-obesit...Here we compare the efficacy of anti-obesity drugs alone or combined with exercise training on body weight and exercise capacity of obese patients.Randomized clinical trials that assessed the impact of any anti-obesity drug alone or combined with exercise training on body weight,body fat,fat-free mass and cardiorespiratory fitness in obese patients were retrieved from Pubmed and EMBASE up to May 2024.Risk of bias assessment was performed with RoB 2.0,and the GRADE approach assessed the certainty of evidence(CoE)of each main outcome.We included four publications summing up 202 patients.Two publications used orlistat as an anti-obesity drug treatment,while the other two adopted GLP-1 receptor agonist(liraglutide or tirzepatide)as a pharmacotherapy for weight management.Orlistat combined with exercise was superior to change body weight(mean difference(MD):−2.27 kg;95%CI:−2.86 to−1.69;CoE:very low),fat mass(MD:−2.89;95%CI:−3.87 to−1.91;CoE:very low),fat-free mass(MD:0.56;95%CI:0.40–0.72;CoE:very low),and VO_(2)Peak(MD:2.64;95%CI:2.52–2.76;CoE:very low).GLP-1 receptor agonist drugs combined with exercise had a great effect on body weight(MD:−3.96 kg;95%CI:−5.07 to−2.85;CoE:low),fat mass(MD:−1.76;95%CI:−2.24 to−1.27;CoE:low),fat-free mass(MD:0.50;95%CI:−0.98 to 1.98;CoE:very low)and VO_(2)Peak(MD:2.47;95%CI:1.31–3.63;CoE:very low).The results reported here suggest that exercise training remains an important approach in weight management when combined with pharmacological treatment.展开更多
A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongatio...A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways.Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH,and natural plant compounds are prime drug candidate sources.Here,we found that the phenolic compound(-)-epicatechin,isolated from Theobroma cacao,effectively inhibited FGFR3’s downstream signaling pathways.Transcriptomic analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways.(-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related genes.In femurs isolated from a mouse model(Fgfr3^(Y367C/+))of ACH,we showed that(-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo culture.In vivo,we confirmed that daily subcutaneous injections of(-)-epicatechin to Fgfr3^(Y367C/+) mice increased bone elongation and rescued the primary cilium defects observed in chondrocytes.This modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation.The results of the present proof-of-principle study support(-)-epicatechin as a potential drug for the treatment of ACH.展开更多
Sofosbuvir is one of the new direct-acting antiviral drugs against hepatitis C virus(HCV) infection. This drug has recently been launched into the market, and generic versions of the medication are expected to be prod...Sofosbuvir is one of the new direct-acting antiviral drugs against hepatitis C virus(HCV) infection. This drug has recently been launched into the market, and generic versions of the medication are expected to be produced by local drug producers in some countries. Therefore, new methods are required to control sofosbuvir in pharmaceuticals. In the present study, a new method based on reversed phase(RP)-ultra-high performance liquid chromatography(UHPLC) coupled to diode array detection(DAD) and mass spectrometry(MS) was developed to facilitate the qualitative and quantitative analysis of sofosbuvir in film coated tablets. A wavelength of 260 nm was selected to perform a cost-effective quantification and the method showed adequate linearity,with an R^2 value of 0.9998, and acceptable values of accuracy(75%–102%) and precision(residual standard deviation < 5%). The detection and quantification limits were 0.07 μg/mL and 0.36 μg/mL, respectively.Furthermore, the use of high-resolution MS enabled us to ensure the specificity, check impurities and better sensitivity. Therefore, this methodology promises to be suitable not only for the routine analysis of sofosbuvir in pharmaceutical dosage forms, but also for potential degradants.展开更多
Guava leaves (Psidium guajava ) are popularly known due to their effects antidiabetic, antihypertensive, anti-inflammatory, antidiarrheal, and functional properties. Processes for the concentration of these extracts a...Guava leaves (Psidium guajava ) are popularly known due to their effects antidiabetic, antihypertensive, anti-inflammatory, antidiarrheal, and functional properties. Processes for the concentration of these extracts are necessary since their pharmacological effects are dose-dependent. In this work, guava leaves aqueous extract (GE) concentration was carried out in nanofiltration (NF) equipment. Process performance was evaluated in terms of permeate flux, flux decline modeling, and extract quality (compounds characterization, total phenolic content and antioxidant activity). NF allowed an increase in phenolic compounds next to 20-times, retention coefficients of total phenolic compounds (99%) and enhanced antioxidant capacity (an increase of 4 and 9-fold for ABTS and DPPH, respectively) compared to the initial GE. Forty-two phenolic compounds were identified, being catechin (594.56 mg mL^(−1) ) and vescalagin (295.39 mg mL^(−1) ) the main compounds. All phenolics presented a significant increase (p < 0.05) after the concentration suggesting that NF is efficient for the recovery and concentration of bioactive compounds and poses as an alternative to obtain functional products and improve added value in agro-industrial residues.展开更多
Altered biomechanics due to amputation can contribute to substantial limitations,influencing sporting activities.Individuals with lower extremity amputations or congenital lower limb deficiency are encouraged to parti...Altered biomechanics due to amputation can contribute to substantial limitations,influencing sporting activities.Individuals with lower extremity amputations or congenital lower limb deficiency are encouraged to participate in para-sports.However,to compete in Paralympic sports,the candidate must have an impairment that results in lower extremity loss of function and meets or exceeds the sport's minimum impairment criteria(MIC).This review will focus on the MIC for competitive wheelchair tennis.Limb deficiency is known as one of the MIC used to regulate participation in competitive para-sports since it impacts gait,kinematics,and biomechanics of both the upper and lower body.Notwithstanding,it is questionable whether the MIC concerning limb deficiency is set at the correct level for determining eligibility for participating in Paralympic sports.This study aims to provide an overview of the evidence examining the impact of different partial foot amputation(PFA)levels on gait as a proxy for sporting performance.This scoping review will be based on a 6-step methodological framework and Preferred Reporting Items for Systematic Reviews and Meta-Analysis,extension for scoping reviews(PRISMA-ScR).Studies will be selected from PubMed,Embase,CINAHL,and SPORTDiscus.Two authors will screen the titles/abstracts independently.Selected studies will be scrutinised,and the same authors will extract data.Findings will be relevant to informing the evidence-based development of MIC for lower limb impairment after PFA and may be extrapolated to specific Paralympic sports,including wheelchair tennis.Results will be disseminated through scientific publications and conferences to audiences interested in Paralympic sports.展开更多
基金supported by Brazilian agencies CAPES(Finance Code 001)CNPq through PQ productivity scholarship.
文摘Here we compare the efficacy of anti-obesity drugs alone or combined with exercise training on body weight and exercise capacity of obese patients.Randomized clinical trials that assessed the impact of any anti-obesity drug alone or combined with exercise training on body weight,body fat,fat-free mass and cardiorespiratory fitness in obese patients were retrieved from Pubmed and EMBASE up to May 2024.Risk of bias assessment was performed with RoB 2.0,and the GRADE approach assessed the certainty of evidence(CoE)of each main outcome.We included four publications summing up 202 patients.Two publications used orlistat as an anti-obesity drug treatment,while the other two adopted GLP-1 receptor agonist(liraglutide or tirzepatide)as a pharmacotherapy for weight management.Orlistat combined with exercise was superior to change body weight(mean difference(MD):−2.27 kg;95%CI:−2.86 to−1.69;CoE:very low),fat mass(MD:−2.89;95%CI:−3.87 to−1.91;CoE:very low),fat-free mass(MD:0.56;95%CI:0.40–0.72;CoE:very low),and VO_(2)Peak(MD:2.64;95%CI:2.52–2.76;CoE:very low).GLP-1 receptor agonist drugs combined with exercise had a great effect on body weight(MD:−3.96 kg;95%CI:−5.07 to−2.85;CoE:low),fat mass(MD:−1.76;95%CI:−2.24 to−1.27;CoE:low),fat-free mass(MD:0.50;95%CI:−0.98 to 1.98;CoE:very low)and VO_(2)Peak(MD:2.47;95%CI:1.31–3.63;CoE:very low).The results reported here suggest that exercise training remains an important approach in weight management when combined with pharmacological treatment.
基金This program received a state subsidy managed by the National Research Agency under the “Investments for the Future” Program bearing the reference ANR-10-IAHU-01Some of the work presented here was funded by the European Community’s Seventh Framework Program under grant agreement 602300 (the SYBIL program (https://www.sybil-fp7.eu/) is funded by the MRC (MC_UU_000007/9))
文摘A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways.Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH,and natural plant compounds are prime drug candidate sources.Here,we found that the phenolic compound(-)-epicatechin,isolated from Theobroma cacao,effectively inhibited FGFR3’s downstream signaling pathways.Transcriptomic analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways.(-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related genes.In femurs isolated from a mouse model(Fgfr3^(Y367C/+))of ACH,we showed that(-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo culture.In vivo,we confirmed that daily subcutaneous injections of(-)-epicatechin to Fgfr3^(Y367C/+) mice increased bone elongation and rescued the primary cilium defects observed in chondrocytes.This modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation.The results of the present proof-of-principle study support(-)-epicatechin as a potential drug for the treatment of ACH.
基金the postdoctoral grant associated to the Excellence Project P11-CTS-7625, which was also financed by the previous entity
文摘Sofosbuvir is one of the new direct-acting antiviral drugs against hepatitis C virus(HCV) infection. This drug has recently been launched into the market, and generic versions of the medication are expected to be produced by local drug producers in some countries. Therefore, new methods are required to control sofosbuvir in pharmaceuticals. In the present study, a new method based on reversed phase(RP)-ultra-high performance liquid chromatography(UHPLC) coupled to diode array detection(DAD) and mass spectrometry(MS) was developed to facilitate the qualitative and quantitative analysis of sofosbuvir in film coated tablets. A wavelength of 260 nm was selected to perform a cost-effective quantification and the method showed adequate linearity,with an R^2 value of 0.9998, and acceptable values of accuracy(75%–102%) and precision(residual standard deviation < 5%). The detection and quantification limits were 0.07 μg/mL and 0.36 μg/mL, respectively.Furthermore, the use of high-resolution MS enabled us to ensure the specificity, check impurities and better sensitivity. Therefore, this methodology promises to be suitable not only for the routine analysis of sofosbuvir in pharmaceutical dosage forms, but also for potential degradants.
基金the National Council for Scientific and Technological Development(CNPq-Brazil),grant number[407877/2018-5]Coordination for the Improvement of Higher Level Personnel(CAPES-Brazil)for the financial support and scholarships+1 种基金Vito Verardo thanks the Spanish Ministry of Economy and Competitiveness(MINECO)for“Ramon y Cajal”contract(RYC-2015-18795)the University of Granada for its support(project PPJI2017.16).
文摘Guava leaves (Psidium guajava ) are popularly known due to their effects antidiabetic, antihypertensive, anti-inflammatory, antidiarrheal, and functional properties. Processes for the concentration of these extracts are necessary since their pharmacological effects are dose-dependent. In this work, guava leaves aqueous extract (GE) concentration was carried out in nanofiltration (NF) equipment. Process performance was evaluated in terms of permeate flux, flux decline modeling, and extract quality (compounds characterization, total phenolic content and antioxidant activity). NF allowed an increase in phenolic compounds next to 20-times, retention coefficients of total phenolic compounds (99%) and enhanced antioxidant capacity (an increase of 4 and 9-fold for ABTS and DPPH, respectively) compared to the initial GE. Forty-two phenolic compounds were identified, being catechin (594.56 mg mL^(−1) ) and vescalagin (295.39 mg mL^(−1) ) the main compounds. All phenolics presented a significant increase (p < 0.05) after the concentration suggesting that NF is efficient for the recovery and concentration of bioactive compounds and poses as an alternative to obtain functional products and improve added value in agro-industrial residues.
文摘Altered biomechanics due to amputation can contribute to substantial limitations,influencing sporting activities.Individuals with lower extremity amputations or congenital lower limb deficiency are encouraged to participate in para-sports.However,to compete in Paralympic sports,the candidate must have an impairment that results in lower extremity loss of function and meets or exceeds the sport's minimum impairment criteria(MIC).This review will focus on the MIC for competitive wheelchair tennis.Limb deficiency is known as one of the MIC used to regulate participation in competitive para-sports since it impacts gait,kinematics,and biomechanics of both the upper and lower body.Notwithstanding,it is questionable whether the MIC concerning limb deficiency is set at the correct level for determining eligibility for participating in Paralympic sports.This study aims to provide an overview of the evidence examining the impact of different partial foot amputation(PFA)levels on gait as a proxy for sporting performance.This scoping review will be based on a 6-step methodological framework and Preferred Reporting Items for Systematic Reviews and Meta-Analysis,extension for scoping reviews(PRISMA-ScR).Studies will be selected from PubMed,Embase,CINAHL,and SPORTDiscus.Two authors will screen the titles/abstracts independently.Selected studies will be scrutinised,and the same authors will extract data.Findings will be relevant to informing the evidence-based development of MIC for lower limb impairment after PFA and may be extrapolated to specific Paralympic sports,including wheelchair tennis.Results will be disseminated through scientific publications and conferences to audiences interested in Paralympic sports.
