Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut ...microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome–based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.
Angoroside C is a phenylpropanoid glycoside compound isolated from the dried root of
Hemsl., which possesses the effects of preventing ventricular remodeling, reducing pulmonary oedema, and reducing ...blood pressure, as well as having the properties of anti-platelet aggregation, hepatoprotection and anti-nephritis, etc. However, few investigations have been conducted on the absorption, distribution, metabolism, and excretion (ADME) study of angoroside C. Thus, a fast ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of angoroside C and its metabolite ferulic acid in rat plasma and tissue homogenate. The two analytes were extracted from the biosamples using a simple protein precipitation with acetonitrile. The developed method was validated and successfully applied to the pharmacokinetics, bioavailability and tissue distribution study after the intragastric administration of angoroside C (100 mg/kg) or the intravenous administration of angoroside C (5 mg/kg), respectively. The results showed that angoroside C can be absorbed extremely quickly (
= 15 min), can be eliminated very rapidly (
= 1.26 h), and its oral bioavailability is only about 2.1%. Furthermore, angoroside C was extensively distributed in all main organs (liver, heart, spleen, lung, kidney, and brain), and the highest concentration was detected in the lung 15 min after oral administration. This paper also indicated that angoroside C could be converted to the active metabolite ferulic acid
. The maximum concentrations of ferulic acid in the kidney occurred at 6 h after oral administration. In summary, this study explored some of the pharmacokinetic characteristics of angoroside C
, and the data produced could provide a basis for the further investigation of angoroside C.
Display omitted
•EPDPR was feasible to achieve stable nitrite accumulation and phosphorus removal.•High NTR and PO43−-P removal efficiency of 75.3% and 92.3% were achieved.•High activity of ...DGAONO3-NO2 over DPAONO3 and DGAONO3 was the key to achieve EPDPR.•Cluster I of Defluviicoccus was responsible for the high nitrite accumulation.•EPDPR/anammox might enhanced nutrient removal from nitrate and municipal sewage.
In this study, a novel process was developed by combining endogenous partial denitrification (EPD, NO3−-N → NO2−-N) with denitrifying phosphorus removal (DPR) in an anaerobic/anoxic/aerobic sequencing batch reactor (SBR) to achieve a stable nitrite accumulation and phosphorus removal from high-strength nitrate (NO3−-N: 186.5 mg/L) and municipal wastewater (NH4+-N: 52.6 mg/L, chemical oxygen demand (COD): 242.7 mg/L). After 138-day, high nitrate-to-nitrite transformation ratio (NTR) of 75.3% and PO43−-P removal efficiency of 92.3% were achieved by controlling the anaerobic drainage ratio and anoxic/aerobic durations. During the anaerobic stage (2.5 h), carbon source in raw municipal wastewater was efficiently utilized by phosphorus-and-glycogen accumulating organisms (PAOs and GAOs) to enhance intracellular carbon storage (69.9% in anaerobic COD consumption), providing sufficient carbons for subsequent anoxic EPD and DPR. During the anoxic stage (2.5 h), high activity of DGAONO3-NO2 (denitrifying GAOs conducting NO3−-N → NO2−-N) over DPAONO3 and DGAONO3 (DPAOs and DGAOs conducting NO3−-N → N2) in nitrate denitrification (77.7% > 8.2% and 5.7%) facilitated the nitrite accumulation and phosphorus uptake. In the last short aerobic stage (10 min), further phosphorus was removed by aerobic PAOs without initiating ammonia/nitrite oxidation. Thus, effluent NO2−-N/NH4+-N ratio of 1.02:1 (close to the theoretical value of 1.32:1 for anammox process) with limited NO3−-N, PO43−-P and COD (1.8, 0.4 and 23.5 mg/L, respectively) were obtained. This provides the potential for advanced nutrient removal from nitrate and municipal wastewaters by combining EPDPR with anammox. Microbial community analysis revealed that Cluster I of Defluviicoccus-GAO group (∼7%) dominated the high nitrite accumulation performance, while Accumulibacter-PAO group (15 ± 3%) was responsible for the P removal performance.
Display omitted
•The first integrated EPDPR/anammox achieved nutrient removal from wastewaters.•68.2% NTR and 99.3% P removal were achieved via EPDPR without complex control.•Competibacter conducted ...nitrite accumulation and Dechloromonas dominated DPR.•Anammox conducted 76.9% TN removal without oxygen and external carbon demands.•Effluent NH4+-N, TN, PO43−-P and COD were respectively 0.4, 6.2, 0.2 and 23.0 mg/L.
This study demonstrated a novel process configuration for sustaining mainstream anammox by integrating the anammox and endogenous partial denitrification-and-phosphorus removal (EPDPR) in two-stage sequencing batch reactors (SBRs). In the EPDPR-SBR, high nitrate-to-nitrite transformation (68.2%) and P removal (99.3%) were achieved by adjusting the anaerobic/anoxic/aerobic durations and influent nitrate concentration, providing a suitable NO2−-N/NH4+-N (∼1.37) for subsequent anammox reaction. In the Anammox-SBR, ∼95% of TN was removed without external carbon and oxygen demands. Satisfactory effluent quality (∼6 mgTN/L and 0.2 mgP/L) achieved in the integrated EPDPR/anammox opens a new window towards the energy-efficient wastewater treatment. Microbial analysis further revealed that Dechloromonas (1.6–9.6%) and Candidatus Competibacter (6.4–5.8%) respectively conducted P removal and NO2−-N production (79.2%) from NO3−-N denitrification in the EPDPR-SBR, whereas Candidatus Kuenenia (7.0–29.7%) dominated NO2−-N and NH4+-N removal (91.3% and 99.5%) in the Anammox-SBR, with 10 genera identified as denitrifying bacteria (0.6–8.1%) further reduced 18.9% of the produced NO3−-N.
Display omitted
•A novel DPR-SPNED process was established to treat municipal and nitrate sewages.•High PO43−-P and TN removal (97.5% and 90.8%) was obtained without extra carbon.•Dechloromonas, ...Candidatus Competibacter and Nitrosomonas dominated the DPR-SPNED.•Bottleneck of inefficient carbon use and high NH4+-N residues in DPRs were solved.•Integrating DPR-SPNED in WWTPs was proposed for further nutrient removal.
The feasibility of coupling denitrifying phosphorus removal (DPR) with simultaneous partial nitrification-endogenous denitrification (SPNED) was investigated in a single-sludge sequencing batch reactor for deep-level nutrient removal from municipal and nitrate wastewaters. After 160-day operation, the DPR process simultaneously reduced most PO43−-P and NO3−-N anoxically, and the SPNED process achieved further total nitrogen (TN) removal at low dissolved oxygen condition with TN removal efficiency of 90.8%. The effluent NH4+-N, PO43−-P and TN concentrations were 1.0, 0.1 and 7.2 mg/L, respectively. Microbial analysis revealed that Dechloromonas (6.7%) dominated DPR process, whereas the gradually enriched Nitrosomonas (4.5%) and Candidatus Competibacter (6.8%) conducted SPNED process accompanied with sharply eliminated Nitrospirae (1.4%). Based on these findings, a novel strategy was proposed to achieve further nutrient removal in conventional treatment through integrating the DPR-SPNED process. As a result, ∼100% of extra carbon and ∼10% of oxygen consumptions would be reduced with satisfactory effluent quality.
Arsenic, distributed pervasively in the natural environment, is an extremely toxic substance which can severely impair the normal functions of living cells. Research on the genetic mechanisms of ...arsenic metabolism is of great importance for remediating arsenic-contaminated environments. Many organisms, including bacteria, have developed various strategies to tolerate arsenic, by either detoxifying this harmful element or utilizing it for energy generation. This review summarizes arsenic detoxification as well as arsenic respiratory metabolic pathways in bacteria and discusses novel arsenic resistance pathways in various bacterial strains. This knowledge provides insights into the mechanisms of arsenic biotransformation in bacteria. Multiple detoxification strategies among bacteria imply possible functional relationships among different arsenic detoxification/metabolism pathways. In addition, this review sheds light on the bioremediation of arsenic-contaminated environments and prevention of antibiotic resistance.
Display omitted
•PD could treat saline nitrate sewage by using carbons in municipal wastewater.•High NTR of ~ 80% was achieved with salinity of 1.25 wt% and CODini/NO3-ini of 3.7.•Thauera was ...remained predominant but with abundance decreased to 42.36% (1.25 wt%).•Suitable NO2-eff/NH4+eff (~1.6) provided a possibility for combing PD with anammox.
The effects of inorganic salts on partial denitrification (PD) was investigated in a sequencing batch reactor for simultaneously treating saline nitrate sewage and municipal wastewater. After 230-day operation, a high nitrate-to-nitrite transformation ratio (NTR) of ~ 80% was achieved with the salinity of 1.25 wt% and the initial chemical oxygen demand to nitrate ratio of 3.7. Microbial community analysis revealed that, Thauera was remained predominant in PD system but with a relative abundance decreasing from 53.02% (0.0 wt%) to 42.36% (1.25 wt%). Moreover, as a suitable ratio of nitrite to ammonia (~1.6) in effluent was obtained, it would be a promising method to treat saline nitrate sewage by combing PD with anammox.
Xiao Chai Hu Tang (XCHT) is sold as traditional medicine or dietary supplement in worldwide. To understand metabolism profile of traditional medicine is key point in their logical pharmacological ...research and clinical application. Based on our previous research of the chemical and absorption signature of XCHT in vitro, we proposed a novel strategy to identify the bioactive components of XCHT in vivo. This strategy have two steps: firstly, based on the parents' database in vitro, built-in and editable biotransformations for phase I and phase II metabolism reactions with MassHunter Metabolite ID software (building metabolites database). Secondly, mouse plasma, bile and urine samples were analyzed by UHPLC–ESI-Q-TOF/MS technique, and the absorbed parents and metabolites were compared and identified with the XCHT's digital library using MassHunter Metabolite ID software. In total, 27 parent compounds and 26 metabolites of XCHT were identified in vivo, 2′-O-xylosyl saikosaponin b2 or b1 was reported for the first time. Saponins and their related metabolites were predominantly excreted into the bile, but flavonoids were excreted by both hepatic as well as renal excretion. Flavonoids, saponins, gingerol and their related metabolites were the absorbed components in cardiovascular system and bioactive components of XCHT. Phase I reactions (hydrolysis, hydroxylation and oxidation) and phase II reactions (glucuronidation) were identified and involved in the mouse metabolism of XCHT.
•An integrated UHPLC-ESI-QTOF MS/MS method was developed for screening and identification of metabolism profile of Xiao Chai Hu Tang from in vitro to in vivo.•Flavonoids, saponins, gingerol and their related metabolites demonstrated bioactivities related to the pharmacological actions of Xiao Chai Hu Tang.•Saponins, gingerols and their related metabolites were predominantly excreted into the bile, but flavonoids were excreted by both hepatic as well as renal excretion.
Glioblastoma (GBM) is a highly aggressive cancer that currently lacks effective treatments. Pyroptosis has emerged as a promising therapeutic approach for cancer, but there is still a need for new ...pyroptosis boosters to target cancer cells. In this study, it is reported that Aloe‐emodin (AE), a natural compound derived from plants, can inhibit GBM cells by inducing pyroptosis, making it a potential booster for pyroptosis‐mediated GBM therapy. However, administering AE is challenging due to the blood‐brain barrier (BBB) and its non‐selectivity. To overcome this obstacle, AE@ZIF‐8 NPs are developed, a biomineralized nanocarrier that releases AE in response to the tumor's acidic microenvironment (TAM). Further modification of the nanocarrier with transferrin (Tf) and polyethylene glycol‐poly (lactic‐co‐glycolic acid) (PEG‐PLGA) improves its penetration through the BBB and tumor targeting, respectively. The results show that AE‐NPs (Tf‐PEG‐PLGA modified AE@ZIF‐8 NPs) significantly increase the intracranial distribution and tumor tissue accumulation, enhancing GBM pyroptosis. Additionally, AE‐NPs activate antitumor immunity and reduce AE‐related toxicity. Overall, this study provides a new approach for GBM therapy and offers a nanocarrier that is capable of penetrating the BBB, targeting tumors, and attenuating toxicity.
By wrapping transferrin (Tf) modifies polyethylene glycol‐poly (lactic‐co‐glycolic acid) polymer on the surface of aloe‐emodin (AE) loaded ZIF‐8, a blood–brain barrier penetrating, glioblastoma (GBM) targeting and pyroptosis boosting nanoformulation is developed. The nanoformulation significantly increases the tissue distribution of intracranial and GBM, and enhances the antitumor activity of AE via CASP3/GSDME pathway induced cell pyroptosis and antitumor immune activation.
Many investigators have indicated that overexpression and amplification of matrix metalloproteinase 2 (MMP-2) and extracellular matrix metalloproteinase inducer (EMMPRIN) are independent prognostic ...factors for primary tumors. We studied expression of them in tissues from intrahepatic cholangiocarcinoma (IHCCA) and normal bile ducts, and discussed the occurrence and development of IHCCA. Another goal was to explore possible association of MMP-2 and EMMPRIN with clinicopathologic parameters and prognosis of IHCCA. MMP-2 and EMMPRIN expression in 106 cases of IHCCA tissues and 15 cases of normal bile ducts were examined by immunohistochemical staining. Then, the association of MMP-2 and EMMPRIN expression with clinicopathologic parameters and patients’ prognosis was analyzed. The positive expression levels of MMP-2 and EMMPRIN associated significantly with various clinicopathologic risk factors, such as poor histologic differentiation (
p
= 0.03, 0.02), higher TNM stages (
p
= 0.02, 0.01) and decreased tumor-specific survival. In particular, the tumor-specific survival rate of the patients with MMP-2+/ EMMPRIN+expression was the lowest (
p
< 0.01). Using Cox regression analysis of the 89 patients, the conjoined expressions of MMP-2-/ EMMPRIN-, MMP-2+/ EMMPRIN +, histologic differentiation, and the clinical TNM stages of tumorous tissues were independent prognostic indicators of IHCCA (
p
< 0.01,
p
< 0.01,
p
= 0.02,
p
= 0.01 and
p
= 0.01, respectively). MMP-2 and EMMPRIN expression in primary tumor predicts an unfavorable prognosis in IHCCA, suggesting a crucial role of the two markers in progression of human IHCCA.
PDF
