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Acta Pharmaceutica (Zagreb, Croatia) Jun 2024At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising...
At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising the development of patient-specific delivery systems and thus the provision of efficient and sustainable drugs. Protein drugs for subcutaneous administration, by allowing less frequent application, represent one of the most important parts of the pharmaceutical field, but their development is inevitably faced with obstacles in providing protein stability and suitable formulation viscosity. To gain further knowledge and fill the gaps in the already constructed data platform for the development of monoclonal antibody formulations, we designed a study that examines small model proteins, bovine serum albumin. The main aim of the presented work is to evaluate the effect of protein concentrations on critical quality attributes of both, pre-lyophilised liquid formulations, and lyophilised products. Through the study, the hypothesis that increasing protein concentration leads to higher viscosity and higher reconstitution time without affecting the stability of the protein was confirmed. The most important finding is that sucrose plays a key role in the lyophilisation of investigated protein, nevertheless, it can be predicted that, to ensure the beneficial effect of mannitol, its amount has to prevail over the amount of sucrose.
Topics: Freeze Drying; Serum Albumin, Bovine; Viscosity; Drug Compounding; Humans; Sucrose; Drug Stability; Chemistry, Pharmaceutical; Excipients; Mannitol; Protein Stability
PubMed: 38815206
DOI: 10.2478/acph-2024-0013 -
Skeletal Muscle May 2024Intramuscular fat (IMAT) infiltration, pathological adipose tissue that accumulates between muscle fibers, is a shared hallmark in a diverse set of diseases including... (Comparative Study)
Comparative Study
Intramuscular fat (IMAT) infiltration, pathological adipose tissue that accumulates between muscle fibers, is a shared hallmark in a diverse set of diseases including muscular dystrophies and diabetes, spinal cord and rotator cuff injuries, as well as sarcopenia. While the mouse has been an invaluable preclinical model to study skeletal muscle diseases, they are also resistant to IMAT formation. To better understand this pathological feature, an adequate pre-clinical model that recapitulates human disease is necessary. To address this gap, we conducted a comprehensive in-depth comparison between three widely used mouse strains: C57BL/6J, 129S1/SvlmJ and CD1. We evaluated the impact of strain, sex and injury type on IMAT formation, myofiber regeneration and fibrosis. We confirm and extend previous findings that a Glycerol (GLY) injury causes significantly more IMAT and fibrosis compared to Cardiotoxin (CTX). Additionally, females form more IMAT than males after a GLY injury, independent of strain. Of all strains, C57BL/6J mice, both females and males, are the most resistant to IMAT formation. In regard to injury-induced fibrosis, we found that the 129S strain formed the least amount of scar tissue. Surprisingly, C57BL/6J of both sexes demonstrated complete myofiber regeneration, while both CD1 and 129S1/SvlmJ strains still displayed smaller myofibers 21 days post injury. In addition, our data indicate that myofiber regeneration is negatively correlated with IMAT and fibrosis. Combined, our results demonstrate that careful consideration and exploration are needed to determine which injury type, mouse model/strain and sex to utilize as preclinical model especially for modeling IMAT formation.
Topics: Animals; Male; Female; Mice, Inbred C57BL; Regeneration; Muscle, Skeletal; Mice; Adipose Tissue; Fibrosis; Disease Models, Animal; Sex Characteristics; Species Specificity; Glycerol; Mice, 129 Strain
PubMed: 38812056
DOI: 10.1186/s13395-024-00344-4 -
BMC Plant Biology May 2024Salinity stress, an ever-present challenge in agriculture and environmental sciences, poses a formidable hurdle for plant growth and productivity in saline-prone regions...
Salinity stress, an ever-present challenge in agriculture and environmental sciences, poses a formidable hurdle for plant growth and productivity in saline-prone regions worldwide. Therefore, this study aimed to explore the effectiveness of trehalose and mannitol induce salt resistance in wheat seedlings. Wheat grains of the commercial variety Sakha 94 were divided into three groups : a group that was pre-soaked in 10 mM trehalose, another group was soaked in 10 mM mannitol, and the last was soaked in distilled water for 1 hour, then the pre soaked grains cultivated in sandy soil, each treatment was divided into two groups, one of which was irrigated with 150 mM NaCl and the other was irrigated with tap water. The results showed that phenols content in wheat seedlings increased and flavonoids reduced due to salt stress. Trehalose and mannitol cause slight increase in total phenols content while total flavonoids were elevated highy in salt-stressed seedlings. Furthermore, Trehalose or mannitol reduced salt-induced lipid peroxidation. Salt stress increases antioxidant enzyme activities of guaiacol peroxidase (G-POX), ascorbate peroxidase (APX), and catalase (CAT) in wheat seedlings, while polyphenol oxidase (PPO) unchanged. Trehalose and mannitol treatments caused an increase in APX, and CAT activities, whereas G-POX not altered but PPO activity were decreased under salt stress conditions. Molecular docking confirmed the interaction of Trehalose or mannitol with peroxidase and ascorbic peroxidase enzymes. Phenyl alanine ammonia layase (PAL) activity was increased in salt-stressed seedlings. We can conclude that pre-soaking of wheat grains in 10 mM trehalose or mannitol improves salinity stress tolerance by enhancing antioxidant defense enzyme and/or phenol biosynthesis, with docking identifying interactions with G-POX, CAT, APX, and PPO.
Topics: Triticum; Trehalose; Seedlings; Mannitol; Salt Tolerance; Molecular Docking Simulation; Antioxidants; Salt Stress; Flavonoids; Phenols
PubMed: 38811894
DOI: 10.1186/s12870-024-04964-2 -
Medical Sciences (Basel, Switzerland) Apr 2024Maintaining a healthy lifestyle can extend life expectancy and improve a person's health status. In addition to physical activity and bad habits related to smoking and...
Maintaining a healthy lifestyle can extend life expectancy and improve a person's health status. In addition to physical activity and bad habits related to smoking and alcohol, diet is also a determining factor. Following a healthy diet pattern over time and supporting a healthy body weight contributes to reducing the risk of developing more severe complications associated with very common diseases such as chronic kidney disease (CKD), diabetes, or cardiovascular diseases. The 2015-2020 Dietary Guidelines for Americans promote the adoption of fat-free or low-fat diets and discourage the consumption of foods with added sugar and solid fats, such as ice creams and other frozen desserts. On the other hand, ice cream, from a nutritional and healthy point of view, can be considered a possible food choice, due to its greater palatability and high nutritional content, but its consumption must be scheduled in a balanced diet. In this retrospective study, 36 patients with chronic renal failure were enrolled. Two different diets were proposed (A and B). In Diet B, lemon sorbet was added twice a week as an alternative food to replace fruit or snacks making the diet more varied and palatable. Nutritional status and biohumoral, immunological, and blood parameters were evaluated after 6 months. A statistical analysis shows a significant inter-group difference in creatinine and azotemia between T0 and T1. Intra-group significant differences were found in lymphocytes ( = 0.005) and azotemia ( < 0.001) in Diet A, and in azotemia ( < 0.001) and transferrin ( < 0.001) in Diet B. The results indicated that ice cream represented a good alternative food in both groups of patients regarding nutritional values and patient satisfaction. Furthermore, the treatment with ice cream allowed for better control of azotemia, maintaining stable levels even in patients with advanced CKD. This study concludes that ice cream could exert beneficial effects in addition to CKD patients' dietary regimens.
Topics: Humans; Renal Insufficiency, Chronic; Ice Cream; Female; Male; Middle Aged; Case-Control Studies; Aged; Retrospective Studies; Adult; Nutritional Status
PubMed: 38804378
DOI: 10.3390/medsci12020022 -
Zhongguo Dang Dai Er Ke Za Zhi =... May 2024Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but...
Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but there is a lack of experience in using this medicine in China. This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, including a review of related literature. After diagnosis, the patient was treated with GPB, followed by efficacy follow-up and pharmacological monitoring. The 6-year and 6-month-old male patient exhibited poor speech development, disobedience, temper tantrums, and aggressive behavior. Blood ammonia levels peaked at 327 μmol/L; urine organic acid analysis indicated elevated uracil levels; cranial MRI showed extensive abnormal signals in both cerebral hemispheres. Genetic testing revealed mutation in the gene (c.241T>C, p.S81P). Blood ammonia levels were approximately 43, 80, and 56 μmol/L at 1, 2, and 3 months after starting GPB treatment, respectively. During treatment, blood ammonia was well-controlled without drug-related adverse effects. The patient showed improvement in developmental delays, obedience, temperament, and absence of aggressive behavior.
Topics: Humans; Male; Ornithine Carbamoyltransferase Deficiency Disease; Phenylbutyrates; Child; Glycerol
PubMed: 38802913
DOI: 10.7499/j.issn.1008-8830.2310050 -
Scientific Reports May 2024Novel wound dressings with therapeutic effects are being continually designed to improve the wound healing process. In this study, the structural, chemical, physical,...
Novel wound dressings with therapeutic effects are being continually designed to improve the wound healing process. In this study, the structural, chemical, physical, and biological properties of an electrospun poly glycerol sebacate/poly lactide acid/platelet-rich plasma (PGS/PLA-PRP) nanofibers were evaluated to determine its impacts on in vitro wound healing. Results revealed desirable cell viability in the Fibroblast (L929) and macrophage (RAW-264.7) cell lines as well as human umbilical vein endothelial cells (HUVEC). Cell migration was evident in the scratch assay (L929 cell line) so that it promoted scratch contraction to accelerate in vitro wound healing. Moreover, addition of PRP to the fiber structure led to enhanced collagen deposition (~ 2 times) in comparison with PGS/PLA scaffolds. While by addition PRP to PGS/PLA fibers not only decreased the expression levels of pro-inflammatory cytokines (IL-6 and TNF-α) in RAW-264.7 cells but also led to significantly increased levels of cytokine (IL-10) and the growth factor (TGF-β), which are related to the anti-inflammatory phase (M2 phenotype). Finally, PGS/PLA-PRP was found to induce a significant level of angiogenesis by forming branching points, loops, and tubes. Based on the results obtained, the PGS/PLA-PRP dressing developed might be a promising evolution in skin tissue engineering ensuring improved wound healing and tissue regeneration.
Topics: Platelet-Rich Plasma; Wound Healing; Humans; Polyesters; Animals; Mice; Glycerol; Bandages; Polymers; Human Umbilical Vein Endothelial Cells; Decanoates; Nanofibers; Cell Movement; Cell Line; Cell Survival; RAW 264.7 Cells; Cytokines; Fibroblasts
PubMed: 38797743
DOI: 10.1038/s41598-024-62855-w -
Molecules (Basel, Switzerland) May 2024Erythritol is a polyol with a sweet taste but low energy value. Thanks to its valuable properties, as well as growing social awareness and nutritional trends, its...
Erythritol is a polyol with a sweet taste but low energy value. Thanks to its valuable properties, as well as growing social awareness and nutritional trends, its popularity is growing rapidly. The aim of this study was to increase the effectiveness of erythritol production from glucose using new UV mutants of the yeast obtained in the Wratislavia K1 strain. The ability of the new strains to biosynthesize erythritol and utilize this polyol was examined in shake-flask cultures and fed-batch processes conducted in a stirred tank reactor with a total glucose concentration of 300 and 400 g/L. The Wratislavia K1 strain produced erythritol most efficiently (97.5 g/L; 192 h) at an initial glucose concentration of 250 g/L (total: 300 g/L). New strains were assessed under such conditions, and it was noted that the highest erythritol concentration (145 g/L; 183 h) was produced by the K1UV15 strain. A significant improvement in the erythritol biosynthesis efficiency (148 g/L; 150 h) was achieved upon the increase in (NH)SO to 3.6 g/L. Further, in the culture with such a concentration of the nitrogen source and increased total glucose level (400 g/L), the K1UV15 strain produced 226 g/L of erythritol within 281 h.
Topics: Erythritol; Yarrowia; Glucose; Mutation; Fermentation; Ultraviolet Rays; Bioreactors
PubMed: 38792051
DOI: 10.3390/molecules29102187 -
International Journal of Environmental... Apr 2024Obesity, indicated by Body Mass Index (BMI), is a risk factor for type 2 diabetes. However, its association with glycated hemoglobin (HbA1c), a crucial indicator of...
Obesity, indicated by Body Mass Index (BMI), is a risk factor for type 2 diabetes. However, its association with glycated hemoglobin (HbA1c), a crucial indicator of blood-sugar control, may vary across different populations and disease statuses. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were analyzed. Participants aged 18-79 years with complete information on BMI, diabetes status, and HbA1c were included (n = 4003). Linear regression models were used to assess the association between BMI and HbA1c, adjusting for demographic confounders, smoking status, alcohol consumption, and healthcare access. Among participants without diabetes, BMI was positively associated with HbA1c levels (coefficient: 0.015, 95% CI: 0.01, 0.02; -value < 0.05), after adjusting for potential confounders. However, this association was not significant among those with diabetes (coefficient: -0.005, 95% CI: -0.05, 0.04; -value > 0.1). Our findings suggest a differential relationship between BMI and HbA1c in individuals with and without diabetes. While BMI remains a significant predictor of HbA1c in non-diabetic individuals, its significance diminishes in those with diabetes.
Topics: Humans; Glycated Hemoglobin; Middle Aged; Body Mass Index; Adult; Male; Female; Aged; United States; Young Adult; Adolescent; Nutrition Surveys; Diabetes Mellitus, Type 2; Obesity; Risk Factors
PubMed: 38791732
DOI: 10.3390/ijerph21050517 -
International Journal of Molecular... May 2024Extracts from medicinal plants are widely used in the treatment and prevention of different diseases. is a Balkan endemic species with reported antioxidant and...
Extracts from medicinal plants are widely used in the treatment and prevention of different diseases. is a Balkan endemic species with reported antioxidant and antimicrobial characteristics; however, its phytochemical composition is not well defined. Here, we examined the metabolome of by chromatography-mass spectrometry (GC-MS), ultra-performance liquid chromatography-mass spectrometry (UPLC-MS-MS), and inductively coupled plasma mass spectrometry (ICP-MS). Amino acids, organic acids, sugars, and sugar alcohols were the primary metabolites with the highest levels in the plant extract. Detailed analysis of the sugar content identified high levels of sucrose, glucose, mannose, and fructose. Lipids are primary plant metabolites, and the analysis revealed triacylglycerols as the most abundant lipid group. Potassium (K), magnesium (Mg), zinc (Zn), and calcium (Ca) were the elements with the highest content. The results showed linarin, 3-caffeoil-quinic acid, and rosmarinic acid, as well as a number of polyphenols, as the most abundant secondary metabolites. Among the flavonoids and polyphenols with a high presence were eupatorin, kaempferol, and apigenin-compounds widely known for their bioactive properties. Further, the acute toxicity and potential anti-inflammatory activity of the methanolic extract were evaluated in Wistar rats. No toxic effects were registered after a single oral application of the extract in doses of between 200 and 5000 mg/kg bw. A fourteen-day pre-treatment with methanolic extract of in doses of 250, 400, and 500 mg/kg bw induced anti-inflammatory activity in the 1st, 2nd, and 3rd hours after carrageenan injection in a model of rat paw edema. This effect was also present in the 4th hour only in the group treated with a dose of 500 mg/kg. In conclusion, extract is particularly rich in linarin, rosmarinic acid, and flavonoids (eupatorin, kaempferol, and apigenin). Its methanolic extract induced no toxicity in male Wistar rats after oral application in doses of up to 5000 mg/kg bw. Additionally, treatment with the methanolic extract for 14 days revealed anti-inflammatory potential in a model of rat paw edema on the 1st, 2nd, and 3rd hours after the carrageenan injection. These results show the anti-inflammatory potential of the plant, which might be considered for further exploration and eventual application as a phytotherapeutic agent.
Topics: Animals; Plant Extracts; Male; Anti-Inflammatory Agents; Rats; Rats, Wistar; Methanol; Edema; Sapotaceae; Metabolome
PubMed: 38791434
DOI: 10.3390/ijms25105396 -
Foods (Basel, Switzerland) May 2024This study investigated the potential of microbial fermentative transforming processes in valorizing the cashew apple by-product into a low-alcohol, health-benefiting...
This study investigated the potential of microbial fermentative transforming processes in valorizing the cashew apple by-product into a low-alcohol, health-benefiting beverage. We particularly investigated the use of a non- yeast, DK, as the main targeted microbe. At 30 °C without agitation, DK caused changes in key parameters during the fermentation of cashew apple juice (CAJ) in terms of varied pH values and initial sugar concentrations. This result indicated that pure CAJ, with pH adjusted to 6 and with the original 6.85% (/) total sugar content, was the most feasible condition, as glucose and fructose were mostly consumed at 12 days of fermentation. A co-culture approach with either TISTR 5088 or A14-6 was investigated to improve both physicochemical and fermentation characteristics. Co-fermentation with TISTR 5088 resulted in significantly increased ethanol accumulation to 33.61 ± 0.11 g/L, but diminished bioactive compounds, antioxidant activity, and antidiabetic potential. In contrast, co-fermentation with A14-6 demonstrated excellent outcomes, as it significantly increased sugar consumption and finally remained at only 4.95 g/L compared to DK alone, produced lower levels of ethanol at only 19.47 ± 0.06 g/L, and higher total titratable acid (TTA), resulting in a final pH of 3.6. In addition, co-fermentation with this lactic acid bacterium significantly enhanced bioactive compounds and antioxidant activity and also retained potential antidiabetic properties. These findings highlight the feasibility of using tailored microbial fermentation strategies to produce low-alcohol beverages with enhanced health-promoting properties from CAJ; however, product-development processes following health food regulations and sensory evaluation are necessary.
PubMed: 38790769
DOI: 10.3390/foods13101469