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Proceedings of the National Academy of... Jun 2024The year 2021 marked a decade of holopelagic sargassum (morphotypes I and VIII, and III) stranding on the Caribbean and West African coasts. Beaching of millions of...
The year 2021 marked a decade of holopelagic sargassum (morphotypes I and VIII, and III) stranding on the Caribbean and West African coasts. Beaching of millions of tons of sargassum negatively impacts coastal ecosystems, economies, and human health. Additionally, the La Soufrière volcano erupted in St. Vincent in April 2021, at the start of the sargassum season. We investigated potential monthly variations in morphotype abundance and biomass composition of sargassum harvested in Jamaica and assessed the influence of processing methods (shade-drying vs. frozen samples) and of volcanic ash exposure on biochemical and elemental components. III was the most abundant morphotype across the year. Limited monthly variations were observed for key brown algal components (phlorotannins, fucoxanthin, and alginate). Shade-drying did not significantly alter the contents of proteins but affected levels of phlorotannins, fucoxanthin, mannitol, and alginate. Simulation of sargassum and volcanic ash drift combined with age statistics suggested that sargassum potentially shared the surface layer with ash for ~50 d, approximately 100 d before stranding in Jamaica. Integrated elemental analysis of volcanic ash, ambient seawater, and sargassum biomass showed that algae harvested from August had accumulated P, Al, Fe, Mn, Zn, and Ni, probably from the ash, and contained less As. This ash fingerprint confirmed the geographical origin and drift timescale of sargassum. Since environmental conditions and processing methods influence biomass composition, efforts should continue to improve understanding, forecasting, monitoring, and valorizing sargassum, particularly as strandings of sargassum show no sign of abating.
Topics: Sargassum; Biomass; Ecosystem; Jamaica; Seasons; Volcanic Eruptions
PubMed: 38805287
DOI: 10.1073/pnas.2312173121 -
International Journal of Pharmaceutics May 2024The xerogel pill has been developed as a novel dosage form with dose-adjusting and swallow-assisting functions by using drop freeze-drying (DFD) technique. It was...
The xerogel pill has been developed as a novel dosage form with dose-adjusting and swallow-assisting functions by using drop freeze-drying (DFD) technique. It was double-structured small sphere composed of an inner drug core and an outer dried-gel layer, however, had problem of insufficient physical strength. In this study, it was attempted to use dextrin (DEX), one of oligosaccharides, to strengthen the xerogel pill. DEX was co-dissolved in the dropping fluid in the DFD process and co-loaded in the conventional pill, which was mainly composed of mannitol (MNT) as a filler, to prepare the rigid body. DEX-loaded pill could be successfully prepared with high recovery (>90 %) by optimizing the ratio of DEX and MNT. Further, the representative pills with and without DEX (P-DEX and P-MNT, respectively) were hardening-processed under humidification. The physical strength of P-DEX pill was significantly increased when humidified under severe condition, resulting in enough hardness (>5N) and friability (<1.0 %). Processed P-DEX was found to have dense structure covered with a thick outer shell, which would be formed by interparticle bridge of DEX. It was also found that processed P-DEX pill suppressed initial drug dissolution significantly and exhibited sustained dissolution behavior, suggesting the potential function of bitter taste masking. Processed P-DEX pill had excellent sliding behavior with low friction forces as a result of lubricant effect of xanthan gum (XG) surrounding the pills. Furthermore, the sliding test also suggested that processed P-DEX pill had hard candy-like texture, in contrast unprocessed P-DEX pill had orally disintegrating (OD) tablet-like texture. Various xerogel pills with such different swallowing texture would have a potential to accommodate the children's preferences when taking medication.
PubMed: 38802028
DOI: 10.1016/j.ijpharm.2024.124282 -
International Journal of Pharmaceutics Jun 2024The application of 3D printing technology in the delivery of macromolecules, such as proteins and enzymes, is limited by the lack of suitable inks. In this study, we...
The application of 3D printing technology in the delivery of macromolecules, such as proteins and enzymes, is limited by the lack of suitable inks. In this study, we report the development of novel inks for 3D printing of constructs containing proteins while maintaining the activity of the proteins during and after printing. Different ink formulations containing Pluronic F-127 (20-35 %, w/v), trehalose (2-10 %, w/v) or mannitol, poly (ethylene glycol) diacrylate (PEGDA) (0 or 10 %, w/w), and diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (TPO, 0 or 0.2 mg/mL) were prepared for 3D-microextrusion printing. The F2 formulation that contained β-galactosidase (β-gal) as a model enzyme, Pluronic F-127 (30 %), and trehalose (10 %) demonstrated the desired viscosity, printability, and dose flexibility. The shear-thinning property of the F2 formulation enabled the printing of β-gal containing constructs with a good peak force during extrusion. After 3D printing, the enzymatic activity of the β-gal in the constructs was maintained for an extended period, depending on the construct design and storage conditions. For instance, there was a 50 % reduction in β-gal activity in the two-layer constructs, but only a 20 % reduction in the four-layer construct (i.e., 54.5 ± 1.2 % and 82.7 ± 9.9 %, respectively), after 4 days of storage. The β-gal activity in constructs printed from the F2 formulation was maintained for up to 20 days when stored in sealed bags at room temperatures (21 ± 2 °C), but not when stored unsealed in the same conditions (e.g., ∼60 % activity loss within 7 days). The β-gal from constructs printed from F2 started to release within 5 min and reached 100 % after 20 min. With the design flexibility offered by the 3D printing, the β-gal release from the constructs was delayed to 3 h by printing a backing layer of β-gal-free F5 ink on the constructs printed from the F2 ink. Finally, ovalbumin as an alternative protein was also incorporated in similar ink compositions. Ovalbumin exhibited a release profile like that of the β-gal, and the release can also be modified with different shape design and/or ink composition. In conclusion, ink formulations that possess desirable properties for 3D printing of protein-containing constructs while maintaining the protein activity during and after printing were developed.
Topics: Printing, Three-Dimensional; Ink; beta-Galactosidase; Poloxamer; Polyethylene Glycols; Trehalose; Viscosity; Excipients; Drug Delivery Systems; Mannitol; Technology, Pharmaceutical; Phosphines
PubMed: 38802027
DOI: 10.1016/j.ijpharm.2024.124277 -
International Journal of Pharmaceutics May 2024The dissolution behavior of tablets, particularly those containing poorly water-soluble drugs, is a critical factor in determining their absorption and therapeutic...
The dissolution behavior of tablets, particularly those containing poorly water-soluble drugs, is a critical factor in determining their absorption and therapeutic efficacy. Traditionally, the particle size of excipients has been considered a key property affecting tablet dissolution. However, lurasidone hydrochloride (LH) tablets prepared by similar particle size mannitol, namely M200 (D = 209.68 ± 1.42 μm) and 160C (D = 195.38 ± 6.87 μm), exhibiting significant differences in their dissolution behavior. In order to find the fundamental influential factors of mannitol influencing the dissolution of LH tablets, the properties (particle size, water content, true density, bulk density, tapped density, specific surface area, circularity, surface free energy, mechanical properties and flowability) of five grades mannitol including M200 and 160C were investigated. Principal component analysis (PCA) was used to establish a relationship between mannitol properties and the dissolution behavior of LH. The results demonstrated that specific surface area (SSA) emerged as the key property influencing the dissolution of LH tablets. Moreover, our investigation based on the percolation theory provided further insights that the SSA of mannitol influences the probability of LH-LH bonding and LH infinite cluster formation, resulting in the different percolation threshold states, then led to different dissolution behaviors. Importantly, it is worth noting that these findings do not invalidate previous conclusions, as reducing particle size generally increases SSA, thereby affecting the percolation threshold and dissolution behavior of LH. Instead, this study provides a deeper understanding of the underlying role played by excipient SSA in the dissolution of drug tablets. This study provides valuable guidance for the development of novel excipients aimed at improving drug dissolution functionality.
PubMed: 38802025
DOI: 10.1016/j.ijpharm.2024.124280 -
Antibiotics (Basel, Switzerland) May 2024The increasing rates of morbidity and mortality owing to bacterial infections, particularly have necessitated finding solutions to face this issue. Thus, we elucidated...
The increasing rates of morbidity and mortality owing to bacterial infections, particularly have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7--bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3--alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (, A, and A). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of isolates. Regarding the model, CDE significantly decreased the burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice's survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies.
PubMed: 38786178
DOI: 10.3390/antibiotics13050450 -
Biosensors Apr 2024Antimicrobial resistance (AMR) has become a crucial global health issue. Antibiotic-resistant bacteria can survive after antibiotic treatments, lowering drug efficacy...
Antimicrobial resistance (AMR) has become a crucial global health issue. Antibiotic-resistant bacteria can survive after antibiotic treatments, lowering drug efficacy and increasing lethal risks. A microfluidic water-in-oil emulsion droplet system can entrap microorganisms and antibiotics within the tiny bioreactor, separate from the surroundings, enabling independent assays that can be performed in a high-throughput manner. This study presents the development of a label-free dielectrophoresis (DEP)-based microfluidic platform to sort droplets that co-encapsulate () and ampicillin (Amp) and droplets that co-encapsulate Amp-resistant (AmpR) with Amp only based on the conductivity-dependent DEP force () without the assistance of optical analyses. The 9.4% low conductivity (LC) Luria-Bertani (LB) broth diluted with 170 mM mannitol can maintain and AmpR growth for 3 h and allow Amp to kill almost all , which can significantly increase the LCLB conductivity by about 100 μS/cm. Therefore, the AmpR /9.4%LCLB/Amp where no cells are killed and the /9.4%LCLB/Amp-containing droplets where most of the cells are killed can be sorted based on this conductivity difference at an applied electric field of 2 MHz and 100 V that generates positive . Moreover, the sorting ratio significantly decreased to about 50% when the population of AmpR was equal to or higher than 50% in droplets. The conductivity-dependent DEP-based sorting platform exhibits promising potential to probe the ratio of AmpR in an unknown bacterial sample by using the sorting ratio as an index.
Topics: Escherichia coli; Electrophoresis; Drug Resistance, Bacterial; Ampicillin; Anti-Bacterial Agents; Electric Conductivity; Microfluidic Analytical Techniques; Microbial Sensitivity Tests
PubMed: 38785691
DOI: 10.3390/bios14050218 -
One Health (Amsterdam, Netherlands) Jun 2024Antimicrobial resistance (AMR) is a global public health concern and needs to be monitored for control. In this study, synanthropic rodents trapped from humans and...
Synanthropic rodents and shrews are reservoirs of zoonotic bacterial pathogens and act as sentinels for antimicrobial resistance spillover in the environment: A study from Puducherry, India.
Antimicrobial resistance (AMR) is a global public health concern and needs to be monitored for control. In this study, synanthropic rodents trapped from humans and animal habitats in Puducherry, India, were screened as sentinels for bacterial pathogens of public health importance and antimicrobial resistance spillover. From the trapped rodents and shrews ( = 100) pathogens viz., and were isolated from oropharyngeal and rectal swabs on Mannitol salt, Mac Conkey and Xylose lysine deoxycholate media respectively. The AMR genes in these isolates were screened by PCR. A total of 76, and 19, non were isolated. was isolated in 89 samples and among the ( = 59), 16, were and 29, were A total of 46 MRSA isolates with ( = 40) ( = 6) were detected. Also, 36.84% and 5.3% non isolates were tested to have and genes. AMR genes encoding ESBL [bla in 21, bla in 45 and bla in 11] was tested positive in 77 isolates Among, isolates 44/45 were screened to have AMR genes [ in 13, in 20 and in 11]. Antibiotic sensitivity test confirmed the antimicrobial resistance. Isolation of pathogens of public health importance and demonstration of genetic elements conferring antimicrobial resistance in the synanthropic rodents confirms that they act as reservoirs and appropriate sentinels to monitor AMR spillover in the environment.
PubMed: 38784598
DOI: 10.1016/j.onehlt.2024.100759 -
Journal of Microbiology and... Jun 2024Peatlands are marginal agricultural lands due to highly acidic soil conditions and poor drainage systems. Drought stress is a big problem in peatlands as it can affect...
Peatlands are marginal agricultural lands due to highly acidic soil conditions and poor drainage systems. Drought stress is a big problem in peatlands as it can affect plants through poor root development, so technological innovations are needed to increase the productivity and sustainability of upland rice on peatlands. Rhizobacteria can overcome the effects of drought stress by altering root morphology, regulating stress-responsive genes, and producing exopolysaccharides and indole acetic acid (IAA). This study aimed to determine the ability of rhizobacteria in upland rice to produce exopolysaccharides and IAA, identify potential isolates using molecular markers, and prove the effect of rhizobacteria on viability and vigor index in upland rice. Rhizobacterial isolates were grown on yeast extract mannitol broth (YEMB) medium for exopolysaccharides production testing and Nutrient Broth (NB)+L-tryptophan medium for IAA production testing. The selected isolates identify using sequence 16S rRNA. The variables observed in testing the effect of rhizobacteria were germination ability, vigour index, and growth uniformity. EPS-1 isolate is the best production of exopolysaccharides (41.6 mg/ml) and IAA (60.83 ppm). The isolate EPS-1 was identified as using 16S rRNA sequencing and phylogenetic analysis. The isolate EPS-1 can increase the viability and vigor of upland rice seeds. is more adaptive and has several functional properties that can be developed as a potential bioagent or biofertilizer to improve soil nutrition, moisture and enhance plant growth. The use of rhizobacteria can reduce dependence on the use of synthetic materials with sustainable agriculture.
Topics: Oryza; Indoleacetic Acids; Phylogeny; Polysaccharides, Bacterial; Soil Microbiology; RNA, Ribosomal, 16S; Droughts; Plant Roots; Stress, Physiological; Klebsiella; Germination
PubMed: 38783698
DOI: 10.4014/jmb.2401.01035 -
Heliyon May 2024Olanzapine is one of the atypical antipsychotic agents which is being increasingly used, and it is synthetic derivative of thienobenzodiazepine with antipsychotic, and...
Olanzapine is one of the atypical antipsychotic agents which is being increasingly used, and it is synthetic derivative of thienobenzodiazepine with antipsychotic, and antinausea, and antiemetic activities. Olanzapine overdose is mainly associated with the development of anticholinergic toxicity and is characterized by central nervous system (CNS) suppression, tachycardia, and delirium. As little is yet known about the effects of this agent in toxic doses, it is important to report the features of overdose. Herein, we reported a 28-year-old male with a history of mental illness and substance abuse, who was admitted in a comatose state with generalized tonic-clonic seizures. Head computed tomography (CT) and cerebrospinal fluid (CSF) analysis revealed significant cerebral edema and raised intracranial pressure, indicative of olanzapine-induced neurotoxicity. Management involved immediate cessation of olanzapine, administration of intravenous mannitol for cerebral edema, and supportive care. The patient's condition gradually improved with these interventions. Elevated olanzapine plasma concentration confirmed the diagnosis of overdose. Cranial pressure-lowering treatment has a certain effect on improving the condition of patients.
PubMed: 38778957
DOI: 10.1016/j.heliyon.2024.e30201 -
F1000Research 2023In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility,...
Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol.
In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. permeation studies and pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the and pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS.
Topics: Carvedilol; Solubility; Biological Availability; Animals; Administration, Oral; Carbazoles; Propanolamines; Permeability; Male; Mannitol; Suspensions; Molecular Dynamics Simulation; Rats
PubMed: 38778814
DOI: 10.12688/f1000research.139228.1