Tetracycline bioremediation using the novel Serratia marcescens strain WW1 isolated from a wastewater treatment plant.

Tetracycline pollution is an emerging threat in aquatic and terrestrial environments because of its widespread applications in human disease, livestock, and aquaculture. Present study, investigated the tetracycline degrading novel Serratia marcescens strain WW1, which was isolated from a wastewater treatment plant (WWTP). Toxicity analysis of tetracycline with strain WW1 indicates that its intermediate metabolites are not toxic for the indicator bacteria and algae. The degradation conditions for the tetracycline optimized using response surface methodology (RSM) were determined as: pH 6.0; temperature, 36 °C; tetracycline concentration, 20 mg L-1; and inoculum size, 100 µL (OD∼0.5). The strain WW1 was able to utilize tetracycline during the growth phase, and it degraded 89.5% of the tetracycline within 48 h. The degradation kinetics suggested the strain perform significant tetracycline removal with half-life (t1/2) 239.04 and 12.44 h in control and treatments. Tetracycline and its intermediates were analyzed using High Performance Liquid Chromatography (HPLC) and Liquid Chromatography-Mass Spectroscopy (LC-MS). It was observed that strain WW1 could efficiently metabolize the tetracycline within 48 h of experiment. The ability of strain WW1 to degrade tetracycline justifies its use as an environmentally-useful bacterium. Therefore, the present study demonstrated that the degradation of antibiotics is possible using indigenous microbial strains.

Synthesis and characterization of lanthanum-based metal organic framework decorated polyaniline for effective adsorption of lead ions from aqueous solutions.

The novel La-MOF@x%PANI composite was synthesized via a two-step procedure with ultra-sonication, and the adsorption mechanism of Pb2+ ions from synthetic aqueous solutions was systematically studied. The Pb2+ adsorption on the La-MOF@x%PANI was evaluated by the Fourier transform infrared spectroscopy, powder X-ray diffraction, field-emission scanning electron microscopy, energy-dispersive X-ray analysis, Brunauer-Emmett-Teller analysis, X-ray photoelectron spectroscopy, and elemental mapping analyses. The effects of the adsorption-influencing parameters, including contact time, solution pH, and co-existing cations on the maximum adsorption capacity of Pb2+ onto the prepared composite material were investigated. Moreover, the adsorption of Pb2+ ions could be eliminated with rapid adsorption kinetics using the water-stable La-MOF@x%PANI composite. The as-synthesized La-MOF@50%PANI exhibited excellent adsorption performance toward Pb2+ ions with an extraordinary adsorption capacity of 185.19 mg/g at pH 6. The Pb2+ adsorption onto the La-MOF@x%PANI composite follows the pseudo-second-order kinetics and fits well with the Langmuir isotherm model, indicating the Pb2+ adsorption depended on the solution pH as the adsorption mechanism was mainly governed by the electrostatic attraction. Notably, La-MOF@x%PANI composite possesses outstanding regeneration ability and stability after up to four successive cycles. The satisfactory findings reflect that the La-MOF@50%PANI hybrid composite holds a great promise for remediating Pb2+ ions from aqueous environments.

Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species.

Iron plays an important role in macrophage polarization by altering metabolic and redox status. However, the impact of iron on the immune status of macrophages is still controversial. In this study, we report that ferric ammonium citrate (FAC) upregulates PD-L1 expression in macrophages. FAC not only altered the phenotype of macrophages but also led to enriching immune-modulatory T cell subsets. Since iron is known to be a constituent of coenzymes facilitating metabolic processes in mitochondria, we examined the metabolic status of FAC-overloaded macrophages by measuring the oxygen consumption rate (OCR) and the represented coenzyme, aconitase. In addition to enhancement of metabolic processes, FAC accelerated the Fenton reaction in macrophages, which also contributed to the facilitation of oxygen consumption. We reasoned that the enhancement of the OCR leads to the production of reactive oxygen species (ROS), which are directly linked to PD-L1 induction. Using ferrostatin, rotenone, and N-acetyl-L-cysteine, we confirmed that metabolic and redox regulation is responsible for FAC-mediated PD-L1 expression. Furthermore, we suggested that FAC-induced ROS production may explain FAC-mediated pro- and anti-inflammatory responses in macrophages. These findings may extend our understanding of regulating iron concentration during immune checkpoint therapy in cancer patients.

Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model.

Immune checkpoints such as programmed death-1 (PD-1) have been proven as antitumor targets by enhancing cytotoxic T cell activity. All immune checkpoint blockades are antibody therapeutics that have large size and high affinity, as well as known immune-related side effects and low responses. To overcome the limitation of antibody therapeutics, we have explored PD-1/PD-L1 (programmed death-ligand 1) blockades in traditional oriental medicine, which has a long history but has not yet studied PD-1/PD-L1 blockades. Sanguisorbae Radix extract (SRE) blocked PD-1 and PD-L1 binding in competitive ELISA. SRE effectively inhibited the PD-1/PD-L1 interaction, thereby improving T cell receptor (TCR) signaling and the NFAT-mediated luciferase activity of T cells. SRE treatment reduced tumor growth in the humanized PD-L1 MC38 cell allograft humanized PD-1 mouse model. Additionally, the combination of SRE and pembrolizumab (anti-PD-1 antibody) suppressed tumor growth and increased infiltrated cytotoxic T cells to a greater extent did either agent alone. This study showed that SRE alone has anticancer effects via PD-1/PD-L1 blockade and that the combination therapy of SRE and pembrolizumab has enhanced immuno-oncologic effects.

Anticancer Effect of Salvia plebeia and Its Active Compound by Improving T-Cell Activity via Blockade of PD-1/PD-L1 Interaction in Humanized PD-1 Mouse Model.

Immune checkpoint inhibitors, increasingly used to treat malignant tumors, are revolutionizing cancer treatment by improving the patient survival expectations. Despite the high antitumor efficacy of antibody therapeutics that bind to PD-1/PD-L1, study on small molecule-based PD-1/PD-L1 inhibitors is required to overcome the side effects of antibody therapeutics caused by their size and affinity. Herein, we investigated antitumor potential of Salvia plebeia R. Br. extract (SPE), which has been used as a traditional oriental medicine and food in many countries, and its components by the blockade of PD-1/PD-L1 interaction. SPE and its component cosmosiin effectively blocked the molecular interaction between PD-1 and PD-L1. SPE also inhibited tumor growth by increasing CD8+ T-cells in the tumor through the activation of tumor-specific T-cells in a humanized PD-1 mouse model bearing hPD-L1 knock-in MC38 colon adenocarcinoma tumor. This finding presents a preclinical strategy to develop small molecule-based anticancer drugs targeting the PD-1/PD-L1 immune checkpoint pathway.

Allithiamine Exerts Therapeutic Effects on Sepsis by Modulating Metabolic Flux during Dendritic Cell Activation.

Recent studies have highlighted that early enhancement of the glycolytic pathway is a mode of maintaining the pro-inflammatory status of immune cells. Thiamine, a well-known co-activator of pyruvate dehydrogenase complex, a gatekeeping enzyme, shifts energy utilization of glucose from glycolysis to oxidative phosphorylation. Thus, we hypothesized that thiamine may modulate inflammation by alleviating metabolic shifts during immune cell activation. First, using allithiamine, which showed the most potent anti-inflammatory capacity among thiamine derivatives, we confirmed the inhibitory effects of allithiamine on the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and maturation process in dendritic cells. We applied the LPS-induced sepsis model to examine whether allithiamine has a protective role in hyper-inflammatory status. We observed that allithiamine attenuated tissue damage and organ dysfunction during endotoxemia, even when the treatment was given after the early cytokine release. We assessed the changes in glucose metabolites during LPS-induced dendritic cell activation and found that allithiamine significantly inhibited glucose-driven citrate accumulation. We then examined the clinical implication of regulating metabolites during sepsis by performing a tail bleeding assay upon allithiamine treatment, which expands its capacity to hamper the coagulation process. Finally, we confirmed that the role of allithiamine in metabolic regulation is critical in exerting anti-inflammatory action by demonstrating its inhibitory effect upon mitochondrial citrate transporter activity. In conclusion, thiamine could be used as an alternative approach for controlling the immune response in patients with sepsis.

Non-toxic nano approach for wastewater treatment using Chlorella vulgaris exopolysaccharides immobilized in iron-magnetic nanoparticles.

The current study, novel magnetic nano-composite particles (Fe3O4@EPS) were successfully synthesized via the co-precipitation of iron (III) chloride and iron (II) sulfate (Fe3O4 nanoparticles) with exopolysaccharides (EPS) derived from the microalga Chlorella vulgaris. The physico-chemical nature of the Fe3O4@EPS was investigated in depth. Transmission electron microscopy (TEM) results estimated the core-shell nature of Fe3O4@EPS aggregated inside the indistinctly layered EPS matrix to be 10-20 nm in size. Scanning electron microscopy-based energy dispersive spectral analysis indicated that elemental Fe was successfully loaded on to the EPS polymeric ion-exchanger at a rate of 63.3% by weight. FT-IR results demonstrated that Fe3O4 nanoparticles were successfully modified by the functional groups present in EPS. Fe3O4@EPS showed a highly magnetic nature at 5.0 emu/g. The XPS survey spectrum, which showed two major peaks at 724.1 and 710.2 eV revealed the elemental composition and electronic structure of Fe3O4 nanoparticles and Fe3O4@EPS. Furthermore, nutrient removal from wastewater was studied. Under optimum conditions (3.5 g/L of Fe3O4@EPS, pH 7.0 and 13 h of incubation) 91% of PO43- and 85% of NH4+were effectively eliminated. These findings demonstrate the potential of Fe3O4@EPS for removing PO43- and NH4+ in wastewater treatment plants.