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This study aimed to investigate the effects of different types and frequencies of physiotherapy on ventilator weaning among patients in the intensive care unit (ICU) and to identify the optimal type and frequency of intervention. PubMed, Cochrane Library, EMBASE, and Airiti Library. Randomized controlled trials that provided information on the dosage of ICU rehabilitation and the parameters related to ventilator weaning were included. Treatment types were classified into conventional physical therapy, exercise-based physical therapy, neuromuscular electrical stimulation (NEMS), progressive mobility, and multi-component. The frequencies were divided into high (≥ 2 sessions/day or NEMS of > 60 minutes/day), moderate (one session/day, 3-7 days/week or NEMS of 30-60 minutes/day), and low (one session/day, < 3 days/week, or NEMS of < 30 minutes/day). Twenty-four articles were included for systematic review and 15 out of 24 articles were analyzed in the meta-analysis. Early rehabilitation, especially the progressive mobility treatment exerted an optimal effect in reducing the ventilator duration in patients in the ICU (standardized mean difference [SMD] = 0.91; 95% confidence interval [CI] = 0.23-1.58; P < 0.01). Regarding the treatment frequency, the high-frequency intervention did not result in a favorable effect on ventilator duration compared with the moderate frequency of treatment (SMD = 0.75; 95% CI = -1.13-2.64; P = 0.43). Early rehabilitation with progressive mobility is highly recommended to decrease the ventilation duration received by patients in the ICU. Depending on clinical resources and the tolerance of patients, the frequency of interventions should reach moderate-to-high frequency, that is, at least one session per day and 3 days a week. Registration number: PROSPERO (CRD42021243331).

Interleukin (IL)-25 is a cytokine released by airway epithelial cells responding to pathogens. Excessive production of reactive oxygen species (ROS) leads to airway inflammation and remodeling in asthma. Mitochondria are the major source of ROS. After stress, defective mitochondria often undergo selective degradation, known as mitophagy. In this study, we examined the effects of IL-25 on ROS production and mitophagy and investigated the underlying mechanisms. The human monocyte cell line was pretreated with IL-25 at different time points. ROS production was measured by flow cytometry. The involvement of mitochondrial activity in the effects of IL-25 on ROS production and subsequent mitophagy was evaluated by enzyme-linked immunosorbent assay, Western blotting, and confocal microscopy. IL-25 stimulation alone induced ROS production and was suppressed by N-acetylcysteine, vitamin C, antimycin A, and MitoTEMPO. The activity of mitochondrial complex I and complex II/III and the levels of p-AMPK and the mitophagy-related proteins were increased by IL-25 stimulation. The CCL-22 secretion was increased by IL-25 stimulation and suppressed by mitophagy inhibitor treatment and PINK1 knockdown. The Th2-like cytokine IL-25 can induce ROS production, increase mitochondrial respiratory chain complex activity, subsequently activate AMPK, and induce mitophagy to stimulate M2 macrophage polarization in monocytes.

Therapeutic antibodies targeting the IGF1R have shown diverse efficacy and safety signals in oncology clinical trials. The success of these agents as future human therapeutics depends on understanding the specific mechanisms by which these antibodies target IGF1R signaling. A panel of well-characterized assays was used to investigate the mechanisms by which ganitumab, a fully human anti-IGF1R antibody undergoing clinical testing, inhibits IGF1R activity. Epitope mapping using IGF1R subdomains localized the ganitumab binding site to the L2 domain. Binding of ganitumab inhibited the high-affinity interaction of IGF-1 and IGF-2 required to activate IGF1R in cells engineered for IGF1R hypersensitivity and in human cancer cell lines, resulting in complete blockade of ligand-induced cellular proliferation. Inhibition of IGF1R activity by ganitumab did not depend on endosomal sequestration, since efficient ligand blockade was obtained without evidence of receptor internalization and degradation. Clinically relevant concentrations of ganitumab also inhibited the activation of hybrid receptors by IGF-1 and IGF-2. Ganitumab was not an agonist of homodimeric IGF1R or hybrid receptors in MCF-7 and COLO 205 cells, but low-level IGF1R activation was detected in cells engineered for IGF1R hypersensitivity. This activation seems biologically irrelevant since ganitumab completely inhibited ligand-driven proliferation. The in vivo efficacy profile of ganitumab was equivalent or better than CR and FnIII-1 domain-specific antibodies, alone or in combination with irinotecan. CR domain-specific antibodies only blocked IGF-1 binding to IGF1R but were more potent than ganitumab at inducing homodimer and hybrid receptor downregulation in vitro, however this difference was less obvious in vivo. No inhibition of hybrid receptors was observed with the FnIII-1 domain antibodies, which were relatively strong homodimer and hybrid agonists. The safety and efficacy profile of ganitumab and other anti-IGF1R antibodies may be explained by the distinct molecular mechanisms by which they inhibit receptor signaling.

Macro- and microalgae-based foods are becoming popular due to their high nutritious value. The algal biomass is enriched with polysaccharides, protein, polyunsaturated fatty acids, carotenoids, vitamins and minerals. However, the most promising fraction is polysaccharides (PS) or their derivatives (as dietary fibers) which are not entirely fermented by colonic bacteria hence act as potential prebiotic. Primarily, algae become famous as prominent protein sources. Recently, these are widely adopted as functional food (e.g., desserts, dairy products, oil-derivatives, pastas etc.) or animal feed (for poultry, cattle, fish etc.). Besides prebiotic and balanced amino acids source, algae derived compounds implied as therapeutics due to comprising bioactive properties to elicit immunomodulatory, antioxidative, anticancerous, anticoagulant, hepato-protective, and antihypertensive responses. Despite the above potentials, broader research determinations are inevitable to explore these algal compounds until microalgae become a business reality for broader and specific applications in all health domains. However, scale up of algal bioprocess remains a major challenge until commercial affordability is accomplished which can be possible by discovering their hidden potentials and increasing their value and application prospects. This review provides an overview of the significance of algae consumption for several health benefits in humans and animals mainly as prebiotics, however their functional food and animal feed potential are briefly covered. Moreover, their potential to develop an algal-based food industry to meet the people's requirements not only as a sustainable food solution with several health benefits but also as therapeutics is inevitable.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR and attenuates PCSK9-mediated reduction in LDLR protein levels, thereby increasing LDL uptake. A combination of mAb1 with a statin increases LDLR levels in HepG2 cells more than either treatment alone. In wild-type mice, mAb1 increases hepatic LDLR protein levels [almost equal to]2-fold and lowers total serum cholesterol by up to 36%: this effect is not observed in LDLR⁻/⁻ mice. In cynomolgus monkeys, a single injection of mAb1 reduces serum LDL-C by 80%, and a significant decrease is maintained for 10 days. We conclude that anti-PCSK9 antibodies may be effective therapeutics for treating hypercholesterolemia.

People with sarcopenic obesity (SO) are characterized by both low muscle mass (sarcopenia) and high body fat (obesity); they have greater risks of metabolic diseases and physical disability than people with sarcopenia or obesity alone. Exercise and nutrition have been reported to be effective for both obesity and sarcopenia management. Thus, we aimed to investigate the effects of exercise and nutrition on body composition, metabolic health, and physical performance in individuals with SO. Studies investigating the effects of exercise and nutrition on body composition, metabolic health, and physical performance in SO individuals were searched from electronic databases up to April 2019. Fifteen studies were included in the meta-analysis. Aerobic exercise decreased body weight and fat mass (FM). Resistance exercise (RE) decreased FM and improved grip strength. The combination of aerobic exercise and RE decreased FM and improved walking speed. Nutritional intervention, especially low-calorie high-protein (LCHP) diet, decreased FM but did not affect muscle mass and grip strength. In addition to exercise training, nutrition did not provide extra benefits in outcome. Exercise, especially RE, is essential to improve body composition and physical performance in individuals with SO. Nutritional intervention with LCHP decreases FM but does not improve physical performance.

The grave environmental, social, and economic concerns over the unprecedented exploitation of non-renewable energy resources have drawn the attention of policy makers and research organizations towards the sustainable use of agro-industrial food and crop wastes. Enzymes are versatile biocatalysts with immense potential to transform the food industry and lignocellulosic biorefineries. Microbial enzymes offer cleaner and greener solutions to produce fine chemicals and compounds. The production of industrially important enzymes from abundantly present agro-industrial food waste offers economic solutions for the commercial production of value-added chemicals. The recent developments in biocatalytic systems are designed to either increase the catalytic capability of the commercial enzymes or create new enzymes with distinctive properties. The limitations of low catalytic efficiency and enzyme denaturation in ambient conditions can be mitigated by employing diverse and inexpensive immobilization carriers, such as agro-food based materials, biopolymers, and nanomaterials. Moreover, revolutionary protein engineering tools help in designing and constructing tailored enzymes with improved substrate specificity, catalytic activity, stability, and reaction product inhibition. This review discusses the recent developments in the production of essential industrial enzymes from agro-industrial food trash and the application of low-cost immobilization and enzyme engineering approaches for sustainable development.

Fish gelatin and its hydrolysates exhibit a variety of biological characteristics, which include antihypertensive and antioxidant properties. In this study, fish gelatins were extracted from extrusion-pretreated tilapia scales, and then subjected to analyses to determine the physicochemical properties and antioxidant activity of the extracted gelatins. Our findings indicate that TSG2 (preconditioned with 1.26% citric acid) possessed the greatest extraction yield, as well as higher antioxidant activities compared with the other extracted gelatins. Hence, TSG2 was subjected to further hydrolyzation using different proteases and ultrafiltration conditions, which yielded four gelatin hydrolysates: TSGH1, TSGH2, TSGH3, and TSGH4. The results showed that TSGH4 (Pepsin + Pancreatin and ultrafiltration < 3000 Da) had a higher yield and greater antioxidant activity in comparison with the other gelatin hydrolysates. As such, TSGH4 was subjected to further fractionation using a Superdex peptide column and two-stage reverse-phase column HPLC chromatography, yielding a subfraction TSGH4-6-2-b, which possessed the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity compared with the other fractions. Further LC-ESI/MS/MS analysis of TSGH4-6-2-b suggested two novel peptides (GYDEY and EPGKSGEQGAPGEAGAP), which could have potential as naturally-occurring peptides with antioxidant properties. These promising results suggest that these antioxidant peptides could have applications in food products, nutraceuticals, and cosmetics.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is associated with secondary hyperparathyroidism (HPT) and serum elevations in the phosphaturic hormone FGF23, which may be maladaptive and lead to increased morbidity and mortality. To determine the role of FGF23 in the pathogenesis of CKD-MBD and development of secondary HPT, we developed a monoclonal FGF23 antibody to evaluate the impact of chronic FGF23 neutralization on CKD-MBD, secondary HPT, and associated comorbidities in a rat model of CKD-MBD. CKD-MBD rats fed a high-phosphate diet were treated with low or high doses of FGF23-Ab or an isotype control antibody. Neutralization of FGF23 led to sustained reductions in secondary HPT, including decreased parathyroid hormone, increased vitamin D, increased serum calcium, and normalization of bone markers such as cancellous bone volume, trabecular number, osteoblast surface, osteoid surface, and bone-formation rate. In addition, we observed dose-dependent increases in serum phosphate and aortic calcification associated with increased risk of mortality in CKD-MBD rats treated with FGF23-Ab. Thus, mineral disturbances caused by neutralization of FGF23 limited the efficacy of FGF23-Ab and likely contributed to the increased mortality observed in this CKD-MBD rat model.

Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction, bronchial hyper-responsiveness, and airway inflammation. The chronic inflammation of the airway is mediated by many cell types, cytokines, chemokines, and inflammatory mediators. Research suggests that exposure to air pollution has a negative impact on asthma outcomes in adult and pediatric populations. Air pollution is one of the greatest environmental risks to health, and it impacts the lungs’ innate and adaptive defense systems. A major pollutant in the air is particulate matter (PM), a complex component composed of elemental carbon and heavy metals. According to the WHO, 99% of people live in air pollution where air quality levels are lower than the WHO air quality guidelines. This suggests that the effect of air pollution exposure on asthma is a crucial health issue worldwide. Macrophages are essential in recognizing and processing any inhaled foreign material, such as PM. Alveolar macrophages are one of the predominant cell types that process and remove inhaled PM by secreting proinflammatory mediators from the lung. This review focuses on macrophages and their role in orchestrating the inflammatory responses induced by exposure to air pollutants in asthma.