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Frontiers in Immunology 2021Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical...
Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established. More than 30 mature commercial technology platforms have been used to create and develop BsAbs based on the heterologous recombination of heavy chains and matching of light chains. The detailed mechanisms of clinical/therapeutic action have been demonstrated with these different types of BsAbs. Three kinds of BsAbs have received market approval, and more than 110 types of BsAbs are at various stages of clinical trials. In this paper, we elaborate on the classic platforms, mechanisms, and applications of BsAbs. We hope that this review can stimulate new ideas for the development of BsAbs and improve current clinical strategies.
Topics: Animals; Antibodies, Bispecific; Antibody Specificity; Binding Sites, Antibody; Biotechnology; Drug Design; Epitopes; Humans; Immunotherapy; Protein Engineering; Recombinant Proteins; Translational Research, Biomedical
PubMed: 34025638
DOI: 10.3389/fimmu.2021.626616 -
International Journal of Molecular... Sep 2022Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of... (Review)
Review
Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.
Topics: Antineoplastic Agents, Immunological; Apoptosis Regulatory Proteins; B7-H1 Antigen; CTLA-4 Antigen; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Ligands; Liver Neoplasms; Lung Neoplasms; Myocarditis; Programmed Cell Death 1 Receptor
PubMed: 36142866
DOI: 10.3390/ijms231810948 -
Nutrients Sep 2019Whey protein (WP) is a dairy food supplement and, due to its effects on fat-free mass (FFM) gain and fat mass (FM) loss, it has been widely consumed by resistance... (Meta-Analysis)
Meta-Analysis
Whey protein (WP) is a dairy food supplement and, due to its effects on fat-free mass (FFM) gain and fat mass (FM) loss, it has been widely consumed by resistance training practitioners. This review analyzed the impact of WP supplementation in its concentrated (WPC), hydrolyzed (WPH) and isolated (WPI) forms, comparing it exclusively to isocaloric placebos. Random effect meta-analyses were performed from the final and initial body composition values of 246 healthy athletes undergoing 64.5 ± 15.3 days of training in eight randomized clinical trials (RCT) collected systematically from five scientific databases. The weighted mean difference (WMD) was statistically significant for FM loss (WMD = -0.96, 95% CI = -1.37, -0.55, < 0.001) and, in the analysis of subgroups, this effect was maintained for the WPC (WMD = -0.63, 95% CI = -1.19, -0.06, = 0.030), with protein content between 51% and 80% (WMD = -1.53; 95% CI = -2.13, -0.93, < 0.001), and only for regular physical activity practitioners (WMD = -0.95; 95% CI = -1.70, -0.19, = 0.014). There was no significant effect on FFM in any of the scenarios investigated ( > 0.05). Due to several and important limitations, more detailed analyses are required regarding FFM gain.
Topics: Athletes; Body Composition; Dietary Supplements; Humans; Whey Proteins
PubMed: 31480653
DOI: 10.3390/nu11092047 -
International Archives of Allergy and... 2023Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food-induced hypersensitivity disorder that occurs mostly in infants. Long... (Meta-Analysis)
Meta-Analysis
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food-induced hypersensitivity disorder that occurs mostly in infants. Long considered a rare disease, a recent increase in physician awareness and publication of diagnosis of guidelines has resulted in an increase in recognized FPIES cases. We aimed to conduct a systematic review of FPIES studies in the past 10 years. A search was conducted on PubMed and Embase in March 2022. Our systematic review focused on 2 domains: (1) the most reported FPIES food triggers; and (2) the resolution rate and median age at resolution of patients with FPIES. We found that cow's milk was the most reported trigger globally. Patterns of the most common triggers varied by country, with fish being one of the most common triggers in the Mediterranean region. We also found that the rate and median age of resolution varied by trigger. Patients with FPIES to cow's milk acquired tolerance at a younger age (most by age 3 years), while fish-FPIES was more persistent (mean resolution by age 37 months-7 years). Overall, many studies found a resolution rate of 60% for any food.
Topics: Female; Animals; Cattle; Food Hypersensitivity; Milk; Enterocolitis; Allergens; Syndrome; Dietary Proteins
PubMed: 36882041
DOI: 10.1159/000529138 -
Saudi Medical Journal Oct 2020Food containing gluten and casein could play a role in autism spectrum disorders (ASD) symptoms. The present review aimed to update the evidence about the role of the...
Food containing gluten and casein could play a role in autism spectrum disorders (ASD) symptoms. The present review aimed to update the evidence about the role of the gluten- and casein-free diet (GCFD) on the management of ASD. Web of Science, Science Direct, Google Scholar, and PubMed databases were used to search for randomized controlled trials (RCT) conducted between January 2000 and February 2020. In total, 9 RCT were included (521 participants) with age range between 2 to 18 years. Four of these studies did not show a significant improvement regarding the symptoms of ASD. The rest of these studies (n=5) showed improvement in communication, stereotyped movements, aggressiveness, language, hyperactivity, tantrums, and signs of attention deficit hyperactivity disorder compared to control group. Hence, the data remains insu cient to support the use of GCFD to improve the symptoms of ASD in children.
Topics: Adolescent; Autism Spectrum Disorder; Caseins; Child; Child, Preschool; Clinical Decision-Making; Diet, Gluten-Free; Diet, Protein-Restricted; Dietary Proteins; Female; Humans; Male
PubMed: 33026043
DOI: 10.15537/smj.2020.10.25308 -
The Journal of Nutrition Jun 2020Increased protein intake has been suggested to improve gains in muscle mass and strength in adults. Furthermore, the timing of protein intake has been discussed as a... (Meta-Analysis)
Meta-Analysis
The Role of Protein Intake and its Timing on Body Composition and Muscle Function in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Increased protein intake has been suggested to improve gains in muscle mass and strength in adults. Furthermore, the timing of protein intake has been discussed as a margin of opportunity for improved prevention measures.
OBJECTIVE
This systematic review investigated the effect of protein supplementation on body composition and muscle function (strength and synthesis) in healthy adults, with an emphasis on the timing of protein intake.
METHODS
Randomized controlled trials were identified using PubMed, Web of Science, CINAHL, and Embase, up to March 2019. For meta-analyses, data on lean body mass (LBM), handgrip strength, and leg press strength were pooled by age group (mean age 18-55 or >55 y) and timing of protein intake. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach.
RESULTS
Data from 65 studies with 2907 participants (1514 men and 1380 women, 13 unknown sex) were included in the review. Twenty-six, 8, and 24 studies were used for meta-analysis on LBM, handgrip strength, and leg press strength, respectively. The protein supplementation was effective in improving (mean difference; 95% CI) LBM in adults (0.62 kg; 0.36, 0.88) and older adults (0.46 kg; 0.23, 0.70), but not handgrip strength (older adults: 0.26 kg; -0.51, 1.04) and leg press strength (adults: 5.80 kg; -0.33, 11.93; older adults: 1.97 kg; -2.78, 6.72). Sensitivity analyses removing studies without exercise training had no impact on the outcomes. Data regarding muscle synthesis were scarce and inconclusive. Subgroup analyses showed no beneficial effect of a specific timing of protein intake on LBM, handgrip strength, and leg press strength.
CONCLUSION
Overall, the results support the positive impact of protein supplementation on LBM of adults and older adults, independently of intake timing. Effects on muscle strength and synthesis are less clear and need further investigation. This systematic review was registered on PROSPERO as CRD42019126742.
Topics: Adolescent; Adult; Body Composition; Dietary Proteins; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Randomized Controlled Trials as Topic; Resistance Training; Young Adult
PubMed: 32232404
DOI: 10.1093/jn/nxaa049 -
Nutrients May 2021A disequilibrium of the gut microbial community has been closely associated with systemic inflammation and metabolic syndromes including type 2 diabetes. While low fibre... (Meta-Analysis)
Meta-Analysis
The Effect of Dietary Fibre on Gut Microbiota, Lipid Profile, and Inflammatory Markers in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
BACKGROUND
A disequilibrium of the gut microbial community has been closely associated with systemic inflammation and metabolic syndromes including type 2 diabetes. While low fibre and high fat diets may lead to dysbiosis of the gut microbiome as a result of the loss of useful microbes, it has been reported that a high fibre diet may prevent the fermentation of protein and may promote eubiosis of gut microbiota.
AIM
This review aims to evaluate the effect of dietary fibre (DF) on gut microbiota, lipid profile, and inflammatory markers in patients with type 2 diabetes.
METHODS
The PRISMA framework was relied on to conduct this systematic review and meta-analysis. Searches were carried out using electronic databases and reference list of articles.
RESULTS
Eleven studies were included in the systematic review, while ten studies were included in the meta-analysis. The findings revealed five distinct areas including the effects of DF on (a) gut microbiota (122 participants); (b) lipopolysaccharides (LPS, 79 participants) and lipopolysaccharides binding protein (LBP, 81 participants); (c) lipid profile; (d) inflammatory markers; and (e) body mass index (BMI, 319 participants). The relative abundance of increased by 0.73 (95% CI: 0.57, 0.89) in the DF group in contrast to the control ( < 0.05). With respect to LPS, the level was lower in the DF group than the control and the difference was significant ( < 0.05). The standardised mean difference for LPS was -0.45 (95% CI: -0.90, -0.01) although the difference between the two groups in relation to LBP was not significant ( = 0.08) and the mean difference was 0.92 (95% CI: -0.12, 1.95). While there was a decrease of -1.05 (95% CI: -2.07, -0.02) with respect to total cholesterol (356 participants) in the DF group as compared with the control ( < 0.05), both groups were not significantly different ( > 0.05) in the other lipid parameters. The difference between the groups was significant ( < 0.05) in relation to C-reactive protein, and the mean difference was 0.43 (95% CI: 0.02, 0.84). This could be due to the short duration of the included studies and differences in participants' diets including the amount of dietary fibre supplements. However, the groups were not significantly different ( > 0.05) with respect to the other inflammatory markers. The meta-analysis of the BMI showed that the DF group decreased by -0.57 (95% CI: -1.02, -0.12) as compared with the control and this was significant ( < 0.01).
CONCLUSION
DF significantly ( < 0.05) increased the relative abundance of and significantly decreased ( < 0.05) LPS, total cholesterol, and BMI as compared with the control. However, DF did not seem to have an effect that was significant on LBP, triglyceride, HDL cholesterol, LDL cholesterol, IL-6, TNF-α, adiponectin, and leptin. These findings have implications for public health in relation to the use of dietary fibre in nutritional interventions and as strategies for managing type 2 diabetes.
Topics: Acute-Phase Proteins; Bifidobacterium; Biomarkers; Body Mass Index; C-Reactive Protein; Carrier Proteins; Databases, Factual; Diabetes Mellitus, Type 2; Dietary Fiber; Dysbiosis; Gastrointestinal Microbiome; Humans; Lipids; Membrane Glycoproteins; Metabolic Syndrome; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 34073366
DOI: 10.3390/nu13061805 -
Sports Medicine (Auckland, N.Z.) Dec 2023Protein supplements are important to maintain optimum health and physical performance, particularly in athletes and active individuals to repair and rebuild their...
Effect of Soy Protein Supplementation on Muscle Adaptations, Metabolic and Antioxidant Status, Hormonal Response, and Exercise Performance of Active Individuals and Athletes: A Systematic Review of Randomised Controlled Trials.
BACKGROUND
Protein supplements are important to maintain optimum health and physical performance, particularly in athletes and active individuals to repair and rebuild their skeletal muscles and connective tissues. Soy protein (SP) has gained popularity in recent years as an alternative to animal proteins.
OBJECTIVES
This systematic review evaluates the evidence from randomised controlled clinical trials of the effects of SP supplementation in active individuals and athletes in terms of muscle adaptations, metabolic and antioxidant status, hormonal response and exercise performance. It also explores the differences in SP supplementation effects in comparison to whey protein.
METHODS
A systematic search was conducted in PubMed, Embase and Web of Science, as well as a manual search in Google Scholar and EBSCO, on 27 June 2023. Randomised controlled trials that evaluated the applications of SPs supplementation on sports and athletic-related outcomes that are linked with exercise performance, adaptations and biomarkers in athletes and physically active adolescents and young adults (14 to 39 years old) were included, otherwise, studies were excluded. The risk of bias was assessed according to Cochrane's revised risk of bias tool.
RESULTS
A total of 19 eligible original research articles were included that investigated the effect of SP supplementation on muscle adaptations (n = 9), metabolic and antioxidant status (n = 6), hormonal response (n = 6) and exercise performance (n = 6). Some studies investigated more than one effect. SP was found to provide identical increases in lean mass compared to whey in some studies. SP consumption promoted the reduction of exercise-induced metabolic/blood circulating biomarkers such as triglycerides, uric acid and lactate. Better antioxidant capacity against oxidative stress has been seen with respect to whey protein in long-term studies. Some studies reported testosterone and cortisol fluctuations related to SP; however, more research is required. All studies on SP and endurance performance suggested the potential beneficial effects of SP supplementation (10-53.3 g) on exercise performance by improving high-intensity and high-speed running performance, enhancing maximal cardiac output, delaying fatigue and improving isometric muscle strength, improving endurance in recreational cyclists, increasing running velocity and decreasing accumulated lactate levels; however, studies determining the efficacy of soy protein on VOmax provided conflicted results.
CONCLUSION
It is possible to recommend SP to athletes and active individuals in place of conventional protein supplements by assessing their dosage and effectiveness in relation to different types of training. SP may enhance lean mass compared with other protein sources, enhance the antioxidant status, and reduce oxidative stress. SP supplementation had an inconsistent effect on testosterone and cortisol levels. SP supplementation may be beneficial, especially after muscle damage, high-intensity/high-speed or repeated bouts of strenuous exercise.
Topics: Adolescent; Adult; Humans; Young Adult; Antioxidants; Athletes; Biomarkers; Dietary Supplements; Hydrocortisone; Lactates; Muscle, Skeletal; Soybean Proteins; Testosterone; Whey Proteins; Randomized Controlled Trials as Topic
PubMed: 37603200
DOI: 10.1007/s40279-023-01899-w -
Advances in Therapy Aug 2022A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) at 1 and 2 years, and overall safety and injection frequency of each treatment.
METHODS
An SLR identifying randomized controlled trials (RCTs) published before June 2021 according to a pre-specified protocol was followed by a Bayesian NMA to compare brolucizumab (6 mg q12w/q8w) against sham and all relevant anti-VEGF regimens. Pooled mean injection frequency, serious adverse ocular events, and discontinuation rates were estimated for each treatment regimen.
RESULTS
Nineteen RCTs were included in NMA base-case analysis. Brolucizumab (6 mg q12w/q8w) with loading-phase (LP) demonstrated superior best-corrected visual acuity (BCVA) gains to sham both at year 1 (mean difference 16.8 [95%CrI 13.3, 20.4]) and year 2 (mean difference 21.2 [95%CrI 17.4, 25.0]) and was comparable to other anti-VEGFs. Brolucizumab (6 mg q12w/q8w) also showed superior retinal thickness reduction to most comparators including ranibizumab (0.5 mg q4w; year 1 mean difference - 50.1 [95%CrI - 70.3, - 29.8]; year 2 mean difference - 49.5 [95%CrI - 70.8, - 28.6]), aflibercept (2 mg q8w; year 1 mean difference - 39.7 [95%CrI - 52.9, - 26.4]; year 2 mean difference - 35.0 [95%CrI - 49.1, - 21.4]), and faricimab (6 mg q16w/q8w; year 1 mean difference - 27.6 [95%CrI - 42.3, - 12.8]). Brolucizumab (6 mg q12w/q8w) showed similar rates of treatment discontinuation and serious and overall adverse events (both years). At year 2, pooled annualized injection frequency was lowest for brolucizumab (6 mg q12w/q8w) and highest for ranibizumab (0.5 mg q4w) at 5.7 and 11.5 injections annually, respectively.
CONCLUSION
Among all licensed anti-VEGF treatments, brolucizumab showed superior reduction in retinal thickness and comparable BCVA gains and discontinuation rates, despite having the lowest injection frequency. The current study provides the most up-to-date, robust comparison of treatments for nAMD.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child, Preschool; Humans; Infant; Intravitreal Injections; Macular Degeneration; Network Meta-Analysis; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 35678996
DOI: 10.1007/s12325-022-02193-3 -
American Journal of Infection Control Jan 2021To collate the evidence on the accuracy parameters of all available diagnostic methods for detecting SARS-CoV-2. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To collate the evidence on the accuracy parameters of all available diagnostic methods for detecting SARS-CoV-2.
METHODS
A systematic review with meta-analysis was performed. Searches were conducted in Pubmed and Scopus (April 2020). Studies reporting data on sensitivity or specificity of diagnostic tests for COVID-19 using any human biological sample were included.
RESULTS
Sixteen studies were evaluated. Meta-analysis showed that computed tomography has high sensitivity (91.9% [89.8%-93.7%]), but low specificity (25.1% [21.0%-29.5%]). The combination of IgM and IgG antibodies demonstrated promising results for both parameters (84.5% [82.2%-86.6%]; 91.6% [86.0%-95.4%], respectively). For RT-PCR tests, rectal stools/swab, urine, and plasma were less sensitive while sputum (97.2% [90.3%-99.7%]) presented higher sensitivity for detecting the virus.
CONCLUSIONS
RT-PCR remains the gold standard for the diagnosis of COVID-19 in sputum samples. However, the combination of different diagnostic tests is highly recommended to achieve adequate sensitivity and specificity.
Topics: Antibodies, Viral; COVID-19; COVID-19 Nucleic Acid Testing; COVID-19 Serological Testing; COVID-19 Testing; Coronavirus Envelope Proteins; Coronavirus RNA-Dependent RNA Polymerase; Humans; Immunoglobulin G; Immunoglobulin M; Lung; SARS-CoV-2; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 32659413
DOI: 10.1016/j.ajic.2020.07.011