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Chinese Medicine Jul 2024Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological... (Review)
Review
Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological treatment of CVD has become one of the most urgent and challenging issues in medical research. Garlic (Allium sativum L.) is one of the oldest plants and is world-renowned for its dietary and medicinal values. Allicin (diallyl thiosulfinate) is one of the primary natural active ingredients in garlic, which has been proven to have powerful cardioprotective effects and mediate various pathological processes related to CVD, such as inflammatory factor secretion, myocardial cell apoptosis, oxidative stress, and more. Therefore, allicin holds a promising application prospect in the treatment of CVD. This review summarized the biological functions of allicin and its potential mechanisms in CVD, including antioxidation, anti-inflammation, and anti-apoptosis effects. Reckoning with these, we delved into recent studies on allicin's cardioprotective effects concerning various CVDs, such as atherosclerosis, hypertension, myocardial infarction, arrhythmia, cardiac hypertrophy, heart failure, and cardiotoxicity. Further, considering the tremendous advancement in nanomedicine, nanotechnology-based drug delivery systems show promise in addressing limitations of allicin's clinical applications, including improving its solubility, stability, and bioavailability. Through this review, we hope to provide a reference for further research on allicin in cardioprotection and drug development.
PubMed: 38956680
DOI: 10.1186/s13020-024-00936-8 -
Microbial Cell Factories Jul 2024Carbonic anhydrase (CA) enzymes facilitate the reversible hydration of CO to bicarbonate ions and protons. Identifying efficient and robust CAs and expressing them in...
BACKGROUND
Carbonic anhydrase (CA) enzymes facilitate the reversible hydration of CO to bicarbonate ions and protons. Identifying efficient and robust CAs and expressing them in model host cells, such as Escherichia coli, enables more efficient engineering of these enzymes for industrial CO capture. However, expression of CAs in E. coli is challenging due to the possible formation of insoluble protein aggregates, or inclusion bodies. This makes the production of soluble and active CA protein a prerequisite for downstream applications.
RESULTS
In this study, we streamlined the process of CA expression by selecting seven top CA candidates and used two bioinformatic tools to predict their solubility for expression in E. coli. The prediction results place these enzymes in two categories: low and high solubility. Our expression of high solubility score CAs (namely CA5-SspCA, CA6-SazCAtrunc, CA7-PabCA and CA8-PhoCA) led to significantly higher protein yields (5 to 75 mg purified protein per liter) in flask cultures, indicating a strong correlation between the solubility prediction score and protein expression yields. Furthermore, phylogenetic tree analysis demonstrated CA class-specific clustering patterns for protein solubility and production yields. Unexpectedly, we also found that the unique N-terminal, 11-amino acid segment found after the signal sequence (not present in its homologs), was essential for CA6-SazCA activity.
CONCLUSIONS
Overall, this work demonstrated that protein solubility prediction, phylogenetic tree analysis, and experimental validation are potent tools for identifying top CA candidates and then producing soluble, active forms of these enzymes in E. coli. The comprehensive approaches we report here should be extendable to the expression of other heterogeneous proteins in E. coli.
Topics: Escherichia coli; Carbonic Anhydrases; Computational Biology; Solubility; Phylogeny; Recombinant Proteins; Carbon Dioxide
PubMed: 38956607
DOI: 10.1186/s12934-024-02463-5 -
BMC Psychiatry Jul 2024Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical...
BACKGROUND
Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS).
METHODS
The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC).
RESULTS
The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels.
CONCLUSIONS
These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.
Topics: Humans; Schizophrenia; Female; Male; Tumor Necrosis Factor-alpha; Psychomotor Agitation; Adult; Receptors, Tumor Necrosis Factor, Type I; Young Adult; Psychiatric Status Rating Scales
PubMed: 38956509
DOI: 10.1186/s12888-024-05796-y -
Scientific Reports Jul 2024We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with...
We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures.
Topics: Excipients; Polysorbates; Vitamin E; Surface-Active Agents; Pyrrolidines; Molecular Dynamics Simulation; Thermodynamics; Hot Melt Extrusion Technology; Vinyl Compounds
PubMed: 38956156
DOI: 10.1038/s41598-024-65978-2 -
Scientific Reports Jul 2024Municipal wastewater treatment systems use the chemical oxygen demand test (COD) to identify organic contaminants in industrial effluents that impede treatment due to...
Municipal wastewater treatment systems use the chemical oxygen demand test (COD) to identify organic contaminants in industrial effluents that impede treatment due to their high concentration. This study reduced the COD levels in tannery wastewater using a multistage treatment process that included Fenton oxidation, chemical coagulation, and nanotechnology based on a synthetic soluble COD standard solution. At an acidic pH of 5, Fenton oxidation reduces the COD concentration by approximately 79%. It achieves this by combining 10 mL/L of HO and 0.1 g/L of FeCl. Furthermore, the author selected the FeCl coagulant for the coagulation process based on the best results of comparisons between different coagulants. At pH 8.5, the coagulation dose of 0.15 g/L achieved the maximum COD removal efficiency of approximately 56.7%. Finally, nano bimetallic Fe/Cu was used to complete the degradation and adsorption of the remaining organic pollutants. The XRD, SEM, and EDX analyses proved the formation of Fe/Cu nanoparticles. A dose of 0.09 g/L Fe/Cu NPs, 30 min of contact time, and a stirring rate of 200 rpm achieve a maximum removal efficiency of about 93% of COD at pH 7.5. The kinetics studies were analyzed using pseudo-first-order P.F.O., pseudo-second-order P.S.O., and intraparticle diffusion models. The P.S.O. showed the best fit among the kinetic models, with an R of 0.998. Finally, the authors recommended that technique for highly contaminated industrial effluents treatment for agriculture or industrial purposes.
PubMed: 38956104
DOI: 10.1038/s41598-024-65162-6 -
Pharmaceutical Research Jul 2024Employing polymer additives is an effective strategy to realize the manipulation of polymorphic transformation. However, the manipulation mechanism is still not clear,...
PURPOSE
Employing polymer additives is an effective strategy to realize the manipulation of polymorphic transformation. However, the manipulation mechanism is still not clear, which limit the precise selection of polymeric excipients and the development of pharmaceutical formulations.
METHODS
The solubility of cimetidine (CIM) in acetonitrile/water mixtures were measured. And the polymorphic transformation from CIM form A to form B with the addition of different polymers was monitored by Raman spectroscopy. Furthermore, the manipulation effect of polymers was determined based on the results of experiments and molecular simulations.
RESULTS
The solubility of form A is consistently higher than that of form B, which indicate that form B is the thermodynamically stable form within the examined temperature range. The presence of polyvinylpyrrolidone (PVP) of a shorter chain length could have a stronger inhibitory effect on the phase transformation process of metastable form, whereas polyethylene glycol (PEG) had almost no impact. The nucleation kinetics experiments and molecular dynamic simulation results showed that only PVP molecules could significantly decrease the nucleation rate of CIM, due to the ability of reducing solute molecular diffusion and solute-solute molecular interaction. A combination of crystal growth rate measurements and calculations of the interaction energies between PVP and the crystal faces of CIM indicate that smaller molecular weight PVP can suppress crystal growth more effectively.
CONCLUSION
PVP K16-18 has more impact on the stabilization of CIM form A and inhibition of the phase transformation process. The manipulation mechanism of polymer additives in the polymorphic transformation of CIM was proposed.
PubMed: 38955998
DOI: 10.1007/s11095-024-03734-x -
Journal of Food Science Jul 2024Soybean protein isolate (SPI) is a highly functional protein source used in various food applications, such as emulsion, gelatin, and food packaging. However, its... (Review)
Review
Soybean protein isolate (SPI) is a highly functional protein source used in various food applications, such as emulsion, gelatin, and food packaging. However, its commercial application may be limited due to its poor mechanical properties, barrier properties, and high water sensitivity. Studies have shown that modifying SPI through glycosylation can enhance its functional properties and biological activities, resulting in better application performance. This paper reviews the recent studies on glycosylation modification of SPI, including its quantification method, structural improvements, and enhancement of its functional properties, such as solubility, gelation, emulsifying, and foaming. The review also discusses how glycosylation affects the bioactivity of SPI, such as its antioxidant and antibacterial activity. This review aims to provide a reference for further research on glycosylation modification and lay a foundation for applying SPI in various fields.
PubMed: 38955774
DOI: 10.1111/1750-3841.17181 -
Journal of Applied Microbiology Jul 2024This study aims to evaluate the storage stability of the freeze-dried recombinant L. lactis NZ3900-fermented milk powder expressing K-ras (Kristen rat sarcoma viral...
AIMS
This study aims to evaluate the storage stability of the freeze-dried recombinant L. lactis NZ3900-fermented milk powder expressing K-ras (Kristen rat sarcoma viral oncogene homolog) mimotopes targeting colorectal cancer in vacuum packaging.
METHODS AND RESULTS
The freeze-dried L. lactis-fermented milk powder stored in 4-ply retortable polypropylene (RCPP)-polyamide (PA)-aluminium (AL)-polyethylene terephthalate (PET) and aluminium polyethylene (ALPE) were evaluated throughout 49 days of accelerated storage (38°C and 90% relative humidity). The fermented milk powder stored in 4-ply packaging remained above 6 log10 CFU g-1 viability, displayed lower moisture content (6.1%), higher flowability (43° angle of repose), water solubility (62%), and survivability of L. lactis after simulated gastric and intestinal digestion (> 82%) than ALPE packaging after 42 days of accelerated storage. K-ras mimotope expression was detected intracellularly and extracellularly in the freeze-dried L. lactis-fermented milk powder upon storage.
CONCLUSIONS
This suggests that fermented milk powder is a suitable food carrier for this live oral vaccine.
PubMed: 38955370
DOI: 10.1093/jambio/lxae162 -
International Journal of Biological... Jun 2024To improve the techno-functional properties of rapeseed protein (RP), this work tried to regulate the molecular structure of RP via inducing the co-assembly of RP with...
To improve the techno-functional properties of rapeseed protein (RP), this work tried to regulate the molecular structure of RP via inducing the co-assembly of RP with zein and whey protein (WP). The results showed that WP and zein mainly regulate the folding process of RP through hydrophobic and disulfide bonds, thereby altering the structural conformation and forming stable complex RP (CRP). WP addition not only increased the number of surface charges and hydrophilicity of proteins, but also decreased their sizes, improved the water solubility, as well as the availability of active groups. These changes significantly increased the foaming capacity (from 60 % to 147 %) and in vitro gastric digestion rate (from 10 % to 60 %) of CRP. Besides, WP also contributed to the formation of gels and the regulation of their textural profiles. Comparatively, zein improved the hydrophobicity of CRP and balanced degree of intermolecular forces, which effectively increased the emulsifying activity index of CRP from 22 m/g to 90 m/g. Zein decreased the hardness, springiness and water-holding capacity of gel, but increased its gumminess and chewiness. Overall, both WP and zein effectively changed the structural conformation of RP, and improved its techno-functional properties, which provides an effective strategy to modify protein.
PubMed: 38955302
DOI: 10.1016/j.ijbiomac.2024.133441 -
International Journal of Biological... Jun 2024The global pandemic caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had profoundly detrimental effects on our society....
The global pandemic caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had profoundly detrimental effects on our society. To combat this highly pathogenic virus, we turned our attention to an abundant renewable natural aromatic polymer found in wood. Through a chemical modification of Eucalyptus and Japanese cedar wood via acidic microwave solvolysis in equivolume mixture of 2 % (w/w) aqueous HSO, ethylene glycol, and toluene at 190 °C. Subsequently, we separated the resulting solvolysis products through extractions with toluene, ethyl acetate, and ethanol. Among these products, the ethyl acetate extract from Eucalyptus wood (eEAE) demonstrated the highest inhibition effects against the novel SARS-CoV-2. We further divided eEAE into four fractions, and a hexane extract from the ethanol-soluble portion, termed eEAE3, exhibited the most substantial inhibitory rate at 93.0 % when tested at a concentration of 0.5 mg/mL. Analyzing eEAE3 using pyrolysis gas chromatography-mass spectrometry revealed that its primary components are derived from lignin. Additionally, HC edited-heteronuclear single quantum coherence nuclear magnetic resonance analysis showed that the solvolysis process cleaved major lignin interunit linkages. Considering the abundance and renewability of lignin, the lignin-derived anti-SARS-CoV-2 agent presents a promising potential for application in suppressing infections within our everyday environment.
PubMed: 38955295
DOI: 10.1016/j.ijbiomac.2024.133556