Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity.

BACKGROUND: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. METHODS: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. RESULTS: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. CONCLUSION: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.

Removal of phosphoglycolate in hyperthermophilic archaea.

Many organisms that utilize the Calvin-Benson-Bassham (CBB) cycle for autotrophic growth harbor metabolic pathways to remove and/or salvage 2-phosphoglycolate, the product of the oxygenase activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). It has been presumed that the occurrence of 2-phosphoglycolate salvage is linked to the CBB cycle, and in particular, the C2 pathway to the CBB cycle and oxygenic photosynthesis. Here, we examined 2-phosphoglycolate salvage in the hyperthermophilic archaeon Thermococcus kodakarensis, an obligate anaerobe that harbors a Rubisco that functions in the pentose bisphosphate pathway. T. kodakarensis harbors enzymes that have the potential to convert 2-phosphoglycolate to glycine and serine, and their genes were identified by biochemical and/or genetic analyses. 2-phosphoglycolate phosphatase activity increased 1.6-fold when cells were grown under microaerobic conditions compared to anaerobic conditions. Among two candidates, TK1734 encoded a phosphatase specific for 2-phosphoglycolate, and the enzyme was responsible for 80% of the 2-phosphoglycolate phosphatase activity in T. kodakarensis cells. The TK1734 disruption strain displayed growth impairment under microaerobic conditions, which was relieved upon addition of sodium sulfide. In addition, glycolate was detected in the medium when T. kodakarensis was grown under microaerobic conditions. The results suggest that T. kodakarensis removes 2-phosphoglycolate via a phosphatase reaction followed by secretion of glycolate to the medium. As the Rubisco in T. kodakarensis functions in the pentose bisphosphate pathway and not in the CBB cycle, mechanisms to remove 2-phosphoglycolate in this archaeon emerged independent of the CBB cycle.

Multiple Roles of Glycerate Kinase-From Photorespiration to Gluconeogenesis, C4 Metabolism, and Plant Immunity.

Plant glycerate kinase (GK) was previously considered an exclusively chloroplastic enzyme of the glycolate pathway (photorespiration), and its sole predicted role was to return most of the glycolate-derived carbon (as glycerate) to the Calvin cycle. However, recent discovery of cytosolic GK revealed metabolic links for glycerate to other processes. Although GK was initially proposed as being solely regulated by substrate availability, subsequent discoveries of its redox regulation and the light involvement in the production of chloroplastic and cytosolic GK isoforms have indicated a more refined regulation of the pathways of glycerate conversion. Here, we re-evaluate the importance of GK and emphasize its multifaceted role in plants. Thus, GK can be a major player in several branches of primary metabolism, including the glycolate pathway, gluconeogenesis, glycolysis, and C4 metabolism. In addition, recently, the chloroplastic (but not cytosolic) GK isoform was implicated as part of a light-dependent plant immune response to pathogen attack. The origins of glycerate are also discussed here; it is produced in several cell compartments and undergoes huge fluctuations depending on light/dark conditions. The recent discovery of the vacuolar glycerate transporter adds yet another layer to our understanding of glycerate transport/metabolism and that of other two- and three-carbon metabolites.

Dynamic regulation and cofactor engineering of escherichia coli to enhance production of glycolate from corn stover hydrolysate.

Glycolic acid is widely employed in chemical cleaning, the production of polyglycolic acid-lactic acid, and polyglycolic acid. Currently, the bottleneck of glycolate biosynthesis lies on the imbalance of metabolic flux and the deficiency of NADPH. In this study, a dynamic regulation system was developed and optimized to enhance the metabolic flux from glucose to glycolate. Additionally, the knockout of transhydrogenase (sthA), along with the overexpression of pyridine nucleotide transhydrogenase (pntAB) and the implementation of the Entner-Doudoroff pathway, were performed to further increase the production of the NADPH, thereby increasing the titer of glycolate to 5.6 g/L. To produce glycolate from corn stover hydrolysate, carbon catabolite repression was alleviated and glucose utilization was accelerated. The final strain, E. coli Mgly10-245, is inducer-free, achieving a glycolate titer of 46.1 g/L using corn stover hydrolysate (77.1 % of theoretical yield). These findings will contribute to the advancement of industrial glycolate production.

Influence of etchant type on the shear bond strength of orthodontic brackets to enamel.

The aim of this study was to evaluate the influence of the type of etchant on the shear bond strength (SBS) of metallic brackets to enamel and the Adhesive Remnant Index (ARI) after debonding. A total of 30 mandibular and maxillary premolars were randomly distributed into groups (n = 10) treated with 1 of 3 enamel surface-conditioning agents: 35% phosphoric acid (PA), 35% glycolic acid (GA), or 35% ferulic acid (FA). The designated acid was applied to the buccal enamel surface of the tooth for 20 seconds, and the tooth was then rinsed with distilled water for 20 seconds and air dried for 5 seconds. A metal bracket was bonded to the prepared surface with light-cured orthodontic resin. After 24 hours, the bracket-tooth interface was submitted to SBS testing in a universal testing machine at a speed of 0.5 mm/min. After debonding, the enamel surface was observed under a stereomicroscope (×20 magnification) to determine the ARI. The generalized linear models showed that the PA and GA groups presented significantly higher SBSs than the FA group (P = 0.0003). The ARI was significantly higher in specimens treated with PA than with the other acids (P < 0.05; Kruskal-Wallis and Dunn tests), with a larger quantity of adhesive remaining adhered to the tooth. Both PA and GA are effective for bonding brackets, but GA resulted in a lower percentage of adhesive remnant adhered to the enamel.

Complete Restoration of Hearing Loss and Cochlear Synaptopathy via Minimally Invasive, Single-Dose, and Controllable Middle Ear Delivery of Brain-Derived Neurotrophic Factor-Poly(dl-lactic acid-co-glycolic acid)-Loaded Hydrogel.

Noise-induced hearing loss (NIHL) often accompanies cochlear synaptopathy, which can be potentially reversed to restore hearing. However, there has been little success in achieving complete recovery of sensorineural deafness using nearly noninvasive middle ear drug delivery before. Here, we present a study demonstrating the efficacy of a middle ear delivery system employing brain-derived neurotrophic factor (BDNF)-poly-(dl-lactic acid-co-glycolic acid) (PLGA)-loaded hydrogel in reversing synaptopathy and restoring hearing function in a mouse model with NIHL. The mouse model achieved using the single noise exposure (NE, 115 dBL, 4 h) exhibited an average 20 dBL elevation of hearing thresholds with intact cochlear hair cells but a loss of ribbon synapses as the primary cause of hearing impairment. We developed a BDNF-PLGA-loaded thermosensitive hydrogel, which was administered via a single controllable injection into the tympanic cavity of noise-exposed mice, allowing its presence in the middle ear for a duration of 2 weeks. This intervention resulted in complete restoration of NIHL at frequencies of click, 4, 8, 16, and 32 kHz. Moreover, the cochlear ribbon synapses exhibited significant recovery, whereas other cochlear components (hair cells and auditory nerves) remained unchanged. Additionally, the cochlea of NE treated mice revealed activation of tropomyosin receptor kinase B (TRKB) signaling upon exposure to BDNF. These findings demonstrate a controllable and minimally invasive therapeutic approach that utilizes a BDNF-PLGA-loaded hydrogel to restore NIHL by specifically repairing cochlear synaptopathy. This tailored middle ear delivery system holds great promise for achieving ideal clinical outcomes in the treatment of NIHL and cochlear synaptopathy.

Impact of Bariatric Surgery on Circulating Metabolites and Cognitive Performance.

INTRODUCTION: Bariatric surgery is an effective intervention to reduce obesity and improve associated comorbidities. However, its effects on cognitive function are still the subject of debate. Given that the bioavailability of circulating metabolites can influence brain metabolism and cognitive performance, we aimed to assess the effects of bariatric surgery on plasma metabolic profiles and cognitive performance. METHODS: We recruited 26 women undergoing gastric bypass surgery. We conducted anthropometric assessments and collected plasma samples for metabolomic analysis. A set of 4 cognitive tests were used to evaluate cognitive performance. Participants were reevaluated 1 year post-surgery. RESULTS: After surgery, attention capacity and executive function were improved, while immediate memory had deteriorated. Regarding metabolic profile, reduction of beta-tocopherol and increase of serine, glutamic acid, butanoic acid, and glycolic acid were observed. To better understand the relationship between cognitive function and metabolites, a cluster analysis was conducted to identify more homogeneous subgroups based on the cognitive performance. We identified cluster 1, which did not show changes in cognitive performance after surgery, and cluster 2, which showed improved attention and executive function, but reduced performance in the immediate memory test. Thus, cluster 2 was more homogeneous group that replicated the results of non-clustered subjects. Analysis of the metabolic profile of cluster 2 confirmed serine, glutamic acid, and glycolic acid as potential metabolites associated with cognitive performance. CONCLUSIONS: Metabolites identified in this study have potential for biomarkers and alternative therapeutic target to prevent obesity-related cognitive decline. KEY POINTS: • Attention capacity and executive function were improved 12 months post bariatric surgery. • Immediate memory was worsened 12 months post bariatric surgery. • Serine, glutamic acid, and glycolic acid are potential metabolites linked to the alteration of cognitive performance.

Efficacy and safety of lasers versus topical medications for acanthosis nigricans and pseudo-acanthosis nigricans treatment: a systematic review.

Acanthosis nigricans (AN) is a cutaneous disorder identified by well-defined pigmented plaques mostly detected on skin folds. Timely diagnosis and treatment of AN is essential as it could be an early manifestation of an underlying condition. The treatment of choice for AN has not been determined yet. Our study aimed to compare the efficacy and safety of various lasers with topical medications, including cream and peel. PubMed, Scopus, and Web of Science databases, as well as the Google Scholar search engine, were thoroughly searched until May 1st, 2023. Study selection was restricted to clinical trials published in English language comparing lasers with topical treatments. This study followed the PRISMA guidelines for systematic reviews and meta-analyses. Out of 1748 studies, Six clinical trials met our inclusion criteria, with 133 patients. We examined laser therapies, including fractional CO2 laser, 1550-nm erbium fiber laser, and long-pulsed alexandrite laser, while the topical treatments comprised glycolic acid (GA) peel, retinoic acid peel, trichloroacetic acid (TCA) peel, and tretinoin cream. In two studies, GA peel demonstrated favorable results compared to fractional CO2 laser. Besides, fractional CO2 laser exhibited efficacy, surpassing TCA peel in AN management. Additionally, a fractional 1550-nm erbium fiber laser displayed superiority over tretinoin cream in reducing average roughness. Similarly, a long-pulsed alexandrite laser demonstrated its effectiveness in axillary AN treatment compared to the combination of tretinoin and ammonium lactate. Overall, the findings revealed that laser therapy was associated with superior results. Moreover, topical treatments are safe and efficacious in AN management.

The phosphorylated pathway of serine biosynthesis affects sperm, embryo, and sporophyte development, and metabolism in Marchantia polymorpha.

Serine metabolism is involved in various biological processes. Here we investigate primary functions of the phosphorylated pathway of serine biosynthesis in a non-vascular plant Marchantia polymorpha by analyzing knockout mutants of MpPGDH encoding 3-phosphoglycerate dehydrogenase in this pathway. Growth phenotypes indicate that serine from the phosphorylated pathway in the dark is crucial for thallus growth. Sperm development requires serine from the phosphorylated pathway, while egg formation does not. Functional MpPGDH in the maternal genome is necessary for embryo and sporophyte development. Under high CO2 where the glycolate pathway of serine biosynthesis is inhibited, suppressed thallus growth of the mutants is not fully recovered by exogenously-supplemented serine, suggesting the importance of serine homeostasis involving the phosphorylated and glycolate pathways. Metabolomic phenotypes indicate that the phosphorylated pathway mainly influences the tricarboxylic acid cycle, the amino acid and nucleotide metabolism, and lipid metabolism. These results indicate the importance of the phosphorylated pathway of serine biosynthesis in the dark, in the development of sperm, embryo, and sporophyte, and metabolism in M. polymorpha.

Glycolate as alternative carbon source for Escherichia coli.

The physiology of different Escherichia coli stains was analyzed for growth with glycolate as a potentially promising sustainable sole source of carbon and energy. Different E. coli strains showed large differences regarding lag phases after provision of glycolate. Whereas E. coli W showed fast adaptation, E. coli BW25113, JM101, and BL21 (DE3) needed extensive time for adaption (up to 30 generations) until the attainable µmax was reached, which, at 30 °C, amounted to 0.20-0.25 h-1 for all strains. The overexpression of genes encoding glycolate degradation did neither overcome the need for adaptation of E. coli BL21 (DE3) nor improve growth of E. coli W. Rather, high level expression of proteins involved in uptake and initial degradation steps had an adverse effect on growth. Overall, the results show a promising capacity of E. coli strains for growth on glycolate.

Disposition of glycolic acid into the embryo following oral administration of ethylene glycol during placentation in the rat and rabbit.

In order to evaluate the role of the placenta in the etiology of ethylene glycol (EG) developmental toxicity, the distribution of EG and its main metabolites, glycolic acid (GA) and oxalic acid (OX), into the conceptus was determined at the beginning and completion of placentation in the rat and rabbit. Two groups (n = 28) of timed-pregnant Wistar rats were administered EG (1000 mg/kg bw/day, oral gavage) from gestation day (GD) 6 to either GD 11 or GD 16; similarly, two groups (n = 28) of timed-pregnant New Zealand White rabbits were administered EG from GD 6 to either GD 10 or GD 19. Four animals from each group were sacrificed at 1, 3, 6, 9, 12, 18, or 24 h after the final administration, and maternal blood, extraembryonic fluid, and embryonic tissue were removed for analysis of EG, GA, and OX. The three analytes were predominantly cleared from all compartments in both species within 24 h. Neither EG nor OX preferentially accumulated into the conceptus compartments, compared with the maternal blood, in either species. Critically, GA was preferentially accumulated from the maternal blood only into the rat embryo at GD 11, but not at GD 16 and not into the rabbit embryo at either GD 10 or GD 19. The accumulation of GA into the rat embryo, and its decline over the course of placentation, is discussed in relation to the expression of monocarboxylate transporter isoforms across the syncytiotrophoblast.

Antitumor active trans­platinum complexes through metabolic stability and enhanced cellular accumulation.

Utilizing isoquinoline as a carrier ligand, we have evaluated the reactivity of selected trans­platinum planar amine (TPA) carboxylate compounds by varying the leaving carboxylate group (acetate, hydroxyacetate, and lactate) in an effort to optimize the cytotoxic and metabolic efficiency. To measure the pharmacological properties of these compounds, a combination of systematic biophysical and biological studies were carried out mainly involving substitution reaction with NAM (N-acetyl-methionine), effects on DNA structural perturbation, cytotoxicity, cellular accumulation, metabolic stability, and cell cycle effects. TPA compounds showed minimal losses in cytotoxic efficacy and outperformed cisplatin after pre-incubation with serum, while displaying a distinct micromolar cytotoxic activity with minimal DNA binding and unaltered cell cycle. Monitoring the TPA compounds with NAM suggests the following trend for the reactivity: hydroxyacetate > lactate > acetate. The same trend was seen for the cytotoxicity in tumor cells and DNA binding, while the rate of drug inactivation/protein binding in cells was not significantly different among these leaving groups. Thus, our results show superior cellular efficacy of TPA compounds and distinct micromolar cytotoxic activities different than cisplatin. Moreover, we found the TPA compounds had prolonged survival and decreased tumor burden compared to the control mice in a relevant human ovarian cancer mouse model with A2780 cells expressing luciferase. Therefore, we propose that further optimization of the basic TPA structure can give further enhanced in vivo activity and may eventually be translated into the development of clinically relevant non-traditional platinum drugs.

Strength of small-bites abdominal wall closure using different suturing methods and materials in an experimental animal model.

PURPOSE: Using small instead of large bites for laparotomy closure results in lower incidence of incisional hernia, but no consensus exists on which suture material to use. This study aimed to compare five different closure strategies in a standardized experimental setting. METHODS: Fifty porcine abdominal walls were arranged into 5 groups: (A) running 2/0 polydioxanone; (B) interlocking 2/0 polydioxanone; (C) running size 0 barbed polydioxanone; (D) running size 0 barbed glycolic acid and trimethylene carbonate; (E) running size 0 suturable polypropylene mesh. The small-bites technique was used for linea alba closure in all. The abdominal walls were divided into a supra- and infra-umbilical half, resulting in 20 specimens per group that were pulled apart in a tensile testing machine. Maximum tensile force and types of suture failure were registered. RESULTS: The highest tensile force was measured when using barbed polydioxanone (334.8 N ± 157.0), but differences did not reach statistical significance. Infra-umbilical abdominal walls endured a significantly higher maximum tensile force compared to supra-umbilical (397 N vs 271 N, p < 0.001). Barbed glycolic acid and trimethylene carbonate failed significantly more often (25% vs 0%, p = 0.008). CONCLUSION: Based on tensile force, both interlocking and running suture techniques using polydioxanone, and running sutures using barbed polydioxanone or suturable mesh, seem to be suitable for abdominal wall closure. Tensile strength was significantly higher in infra-umbilical abdominal walls compared to supra-umbilical. Barbed glycolic acid and trimethylene carbonate should probably be discouraged for fascial closure, because of increased risk of suture failure.

A mycofactocin-associated dehydrogenase is essential for ethylene glycol metabolism by Rhodococcus jostii RHA1.

Ethylene glycol is an industrially important diol in many manufacturing processes and a building block of polymers, such as poly(ethylene terephthalate). In this study, we found that a mycolic acid-containing bacterium Rhodococcus jostii RHA1 can grow with ethylene glycol as a sole source of carbon and energy. Deletion of a putative glycolate dehydrogenase gene (RHA1_ro03227) abolished growth with ethylene glycol, indicating that ethylene glycol is assimilated via glycolate in R. jostii RHA1. Transcriptome sequencing and gene deletion analyses revealed that a gene homologous to mycofactocin (MFT)-associated dehydrogenase (RHA1_ro06057), hereafter referred to as EgaA, is essential for ethylene glycol assimilation. Furthermore, egaA deletion also negatively affected the utilization of ethanol, 1-propanol, propylene glycol, and 1-butanol, suggesting that EgaA is involved in the utilization of various alcohols in R. jostii RHA1. Deletion of MFT biosynthetic genes abolished growth with ethylene glycol, indicating that MFT is the physiological electron acceptor of EgaA. Further genetic studies revealed that a putative aldehyde dehydrogenase (RHA1_ro06081) is a major aldehyde dehydrogenase in ethylene glycol metabolism by R. jostii RHA1. KEY POINTS: • Rhodococcus jostii RHA1 can assimilate ethylene glycol via glycolate • A mycofactocin-associated dehydrogenase is involved in the oxidation of ethylene glycol • An aldehyde dehydrogenase gene is important for the ethylene glycol assimilation.

Percutaneous Intratumoral Immunoadjuvant Gel Increases the Abscopal Effect of Cryoablation for Checkpoint Inhibitor Resistant Cancer.

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, an injectable thermoresponsive gel-based controlled release formulation is developed for the FDA-approved Toll-like-receptor 7 (TLR7) agonist imiquimod ("Imigel") that forms a tumor-resident depot upon injection and contains a contrast agent for visualization under computed tomography (CT). The poly-lactic-co-glycolic acid-polyethylene glycol-poly-lactic-co-glycolic acid (PLGA-PEG-PLGA)-based amphiphilic copolymer gel's underlying micellar nature enables high drug concentration and a logarithmic release profile that is additive with the neo-antigen release from cryoablation, requiring only a single injection. Rheological testing demonstrated the thermoresponsive increase in viscosity at body temperature and radio-opacity via microCT. Its ability to significantly augment the abscopal rate of cryoablation is demonstrated in otherwise immunotherapy resistant metastatic tumors in two aggressive colorectal and breast cancer dual tumor models with an all or nothing response, responders generally demonstrating complete regression of bilateral tumors in 90-day survival studies.

Three Birds, One Stone: An Osteo-Microenvironment Stage-Regulative Scaffold for Bone Defect Repair through Modulating Early Osteo-Immunomodulation, Middle Neovascularization, and Later Osteogenesis.

In order to repair critical-sized bone defects, various polylactic acid-glycolic acid (PLGA)-based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA-based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo-friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone-healing process, an osteo-microenvironment stage-regulative scaffold (P80/D10/M10) is fabricated by incorporating self-developed decellularized bone matrix microparticles (DBM-MPs) and multifunctional magnesium hydroxide nanoparticles (MH-NPs) into PLGA with an optimized proportion using low-temperature rapid prototyping (LT-RP) 3D-printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo-immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo-friendly microenvironment in a stage-matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo-microenvironment stage-regulative scaffold provides a promising treatment for bone defect repair.

Selective detection of ionic liquid fluorescence probes for visual colorimetry of different metal ions.

At present, the fast distinction of different metal ions in pure water media is not only a great challenge, but also drives the protection of water quality in environmental water bodies. In this paper, a novel ionic liquid fluorescent probe Glycolic Acid-L-Arginine (GA-L-Arg) was rationally created and designed through an in-depth study of ionic liquids. It is also used as an innovative multi-ion fluorescent probe for colorimetric detection and separate identification of Fe3+ and Co2+ in aqueous solutions of various metal ions. GA-L-Arg has excellent water solubility due to the strong hydrophilicity of Glycolic Acid and L-Arginine. The probe showed high sensitivity, extremely significant selectivity, and great pH stability for Fe3+ and Co2+ in pure water. The GA-L-Arg structure and the mechanism of Fe3+ and Co2+ detection were analyzed by infrared spectroscopic characterization and quantum chemical calculations. More importantly, the distinct colorimetric partitioning of Fe3+ and Co2+ was performed by the unique extraction of Fe3+ in the presence of the fluorescent probe and buffer solution.

Biodegradable AZ91 magnesium alloy/sirolimus/poly D, L-lactic-co-glycolic acid-based substrate for cardiovascular device application.

Biodegradable drug-eluting stents (DESs) are gaining importance owing to their attractive features, such as complete drug release to the target site. Magnesium (Mg) alloys are promising materials for future biodegradable DESs. However, there are few explorations using biodegradable Mg for cardiovascular stent application. In this present study, sirolimus-loaded poly D, L-lactic-co-glycolic acid (PLGA)-coated/ sirolimus-fixed/AZ91 Mg alloy-based substrate was developed via a layer-by-layer approach for cardiovascular stent application. The AZ91 Mg alloy was prepared through the squeeze casting technique. The casted AZ91 Mg alloy (Mg) was alkali-treated to provide macroporous networks to hold the sirolimus and PLGA layers. The systematic characterization was investigated via electrochemical, optical, physicochemical, and in-vitro biological characteristics. The presence of the Mg17 Al12 phase in the Mg sample was found in the x-ray diffraction system (XRD) spectrum which influences the corrosion behavior of the developed substrate. The alkali treatment increases the substrate's hydrophilicity which was confirmed through static contact angle measurement. The anti-corrosion characteristic of casted-AZ91 Mg alloy (Mg) was slightly less than the sirolimus-loaded PLGA-coated alkali-treated AZ91 Mg alloy (Mg/Na/S/P) substrate. However, dissolution rates for both substrates were found to be controlled at cell culture conditions. Radiographic densities of AZ91 Mg alloy substrates (Mg, Mg/Na, and Mg/Na/S/P) were measured to be 0.795 ± 0.015, 0.742 ± 0.01, and 0.712 ± 0.017, respectively. The star-shaped structure of 12% sirolimus/PLGA ensures the bioavailability of the drugs. Sirolimus release kinetic was fitted up to 80% with the "Higuchi model" for Mg samples, whereas Mg/Na/S/P showed 45% fitting with a zero-order mechanism. The Mg/Na/S/P substrate showed a 70% antithrombotic effect compared to control. Further, alkali treatment enhances the antibacterial characteristic of AZ91 Mg alloy. Also, the alkali-treated sirolimus-loaded substrates (Mg/Na/S and Mg/Na/S/P) inhibit the valvular interstitial cell's growth significantly in in-vitro. Hence, the results imply that sirolimus-loaded PLGA-coated AZ91 Mg alloy-based substrate can be a potential candidate for cardiovascular stent application.

Using anti-PD-L1 antibody conjugated gold nanoshelled poly (Lactic-co-glycolic acid) nanocapsules loaded with doxorubicin: A theranostic agent for ultrasound imaging and photothermal/chemo combination therapy of triple negative breast cancer.

Triple negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and it is difficult to progress through traditional chemotherapy. Therefore, the treatment of TNBC urgently requires agents with effective diagnostic and therapeutic capabilities. In this study, we obtained programmed death-ligand 1 (PD-L1) antibody conjugated gold nanoshelled poly(lactic-co-glycolic acid) (PLGA) nanocapsules (NCs) encapsulating doxorubicin (DOX) (DOX@PLGA@Au-PD-L1 NCs). PLGA NCs encapsulating DOX were prepared by a modified single-emulsion oil-in-water (O/W) solvent evaporation method, and gold nanoshells were formed on the surface by gold seed growth method, which were coupled with PD-L1 antibodies by carbodiimide method. The fabricated DOX@PLGA@Au-PD-L1 NCs exhibited promising contrast enhancement in vitro ultrasound imaging. Furthermore, DOX encapsulated in NCs displayed good pH-responsive and photo-triggered drug release properties. After irradiating 200 µg/mL NCs solution with a laser for 10 min, the solution temperature increased by nearly 23°C, indicating that the NCs had good photothermal conversion ability. The targeting experiments confirmed that the NCs had specific target binding ability to TNBC cells overexpressing PD-L1 molecules. Cell experiments exhibited that the agent significantly reduced the survival rate of TNBC cells through photochemotherapy combination therapy. As a multifunctional diagnostic agent, DOX@PLGA@Au-PD-L1 NCs could be used for ultrasound targeted contrast imaging and photochemotherapy combination therapy of TNBC cells, providing a promising idea for early diagnosis and treatment of TNBC.

Functionalization of poly (lactic-co-glycolic acid) nano­calcium sulphate and fucoidan 3D scaffold using human bone marrow mesenchymal stromal cells for bone tissue engineering application.

This study aimed to functionalize a novel porous PLGA (Poly lactic-co-glycolic acid) composite scaffold in combination with nano­calcium sulphate (nCS) and/or fucoidan (FU) to induce osteogenic differentiation of human bone marrow stromal cells. The composite scaffolds (PLGA-nCS-FU, PLGA-nCS or PLGA-FU) were fabricated and subjected to characterization using Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), Scanning electron microscopy (SEM) and Energy Dispersive X-Ray (EDX). The biocompatibility and osteogenic induction potential of scaffolds on seeded human bone marrow derived mesenchymal stromal cells (hBMSCs) were studied using cell attachment and alamar blue cell viability and alkaline phosphatase (ALP), osteocalcin and osteogenic gene expression, respectively. The composition of different groups was reflected in FTIR, XRD and EDX. The SEM micrographs revealed a difference in the surface of the scaffold before and after FU addition. The confocal imaging and SEM micrographs confirmed the attachment of cells onto all three composite scaffolds. However, the AB assay indicated a significant increase (p < 0.05) in cell viability/proliferation seeded on PLGA-nCS-FU on day 21 and 28 as compared with other combinations. A 2-fold significant increase (p < 0.05) in ALP and OC secretion of seeded hBMSCs onto PLGA-nCS-FU was observed when compared with other combinations. A significant increase in RUNX2, OPN, COL-I and ALP genes were observed in the cells seeded on PLGA-nCS-FU on day 14 and 28 as compared with day 0. In conclusion, the incorporation of both Fucoidan and Nano­calcium sulphate with PLGA showed a promising improvement in the osteogenic potential of hBMSCs. Therefore, PLGA-nCS-FU could be the ideal candidate for subsequent pre-clinical studies to develop a successful bone substitute to repair critical bone defects.