The Clostridium Metabolite P-Cresol Sulfate Relieves Inflammation of Primary Biliary Cholangitis by Regulating Kupffer Cells.

OBJECTIVE: To study the effect and mechanism of the Clostridium metabolite p-Cresol sulfate (PCS) in primary biliary cholangitis (PBC). METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to detect differences in tyrosine, phenylalanine, tryptophan, PCS, and p-Cresyl glucuronide (PCG) between the serum of PBC patients and healthy controls. In vivo experiments, mice were divided into the normal control, PBC group, and PBC tyrosine group. GC-MS was used to detect PCS and PCG. Serum and liver inflammatory factors were compared between groups along with the polarization of liver Kupffer cells. Additionally, PCS was cultured with normal bile duct epithelial cells and Kupffer cells, respectively. PCS-stimulated Kupffer cells were co-cultured with lipopolysaccharide-injured bile duct epithelial cells to detect changes in inflammatory factors. RESULTS: Levels of tyrosine and phenylalanine were increased, but PCS level was reduced in PBC patients, with PCG showing a lower concentration distribution in both groups. PCS in PBC mice was also lower than those in normal control mice. After oral administration of tyrosine feed to PBC mice, PCS increased, liver inflammatory factors were decreased, and anti-inflammatory factors were increased. Furthermore, Kupffer cells in the liver polarized form M1 transitioned to M2. PCS can damage normal bile duct epithelial cells and suppress the immune response of Kupffer cells. But PCS protects bile duct epithelial cells damaged by LPS through Kupffer cells. CONCLUSIONS: PCS produced by Clostridium-metabolized tyrosine reduced PBC inflammation, suggesting that intervention by food, or supplementation with PCS might represent an effective clinical strategy for treating PBC.

Biochar application for greenhouse gas mitigation, contaminants immobilization and soil fertility enhancement: A state-of-the-art review.

Rising global temperature, pollution load, and energy crises are serious problems, recently facing the world. Scientists around the world are ambitious to find eco-friendly and cost-effective routes for resolving these problems. Biochar has emerged as an agent for environmental remediation and has proven to be the effective sorbent to inorganic and organic pollutants in water and soil. Endowed with unique attributes such as porous structure, larger specific surface area (SSA), abundant surface functional groups, better cation exchange capacity (CEC), strong adsorption capacity, high environmental stability, embedded minerals, and micronutrients, biochar is presented as a promising material for environmental management, reduction in greenhouse gases (GHGs) emissions, soil management, and soil fertility enhancement. Therefore, the current review covers the influence of key factors (pyrolysis temperature, retention time, gas flow rate, and reactor design) on the production yield and property of biochar. Furthermore, this review emphasizes the diverse application of biochar such as waste management, construction material, adsorptive removal of petroleum and oil from aqueous media, immobilization of contaminants, carbon sequestration, and their role in climate change mitigation, soil conditioner, along with opportunities and challenges. Finally, this review discusses the evaluation of biochar standardization by different international agencies and their economic perspective.

Kupffer Cells Regulate Natural Killer Cells Via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) Interaction and Cytokines in a Primary Biliary Cholangitis Mouse Model.

BACKGROUND Kupffer cells and natural killer (NK) cells has been identified as contributing factors in the pathogenesis of hepatitis, but the detailed mechanism of these cell types in the pathogenesis of primary biliary cholangitis (PBC) is poorly understood. MATERIAL AND METHODS In this study, polyinosinic: polycytidylic acid (poly I: C), 2-octynoic acid-bovine serum albumin (2OA-BSA) and Freund's adjuvant (FA) were injected to establish a murine PBC model, from which NK cells and Kupffer cells were extracted and isolated. The cells were then co-cultivated in a designed culture system, and then NK group 2, member D (NKG2D), retinoic acid early inducible-1 (RAE-1), F4/80, and cytokine expression levels were detected. RESULTS The results showed close crosstalk between Kupffer cells and NK cells. PBC mice showed increased surface RAE-1 protein expression and Kupffer cell cytokine secretion, which subsequently activated NK cell-mediated target cell killing via NKG2D/RAE-1 recognition, and increased inflammation. NK cell-derived interferon-γ (IFN-γ) and Kupffer cell-derived tumor necrosis factor alpha (TNF-alpha) were found to synergistically regulate inflammation. Moreover, interleukin (IL)-12 and IL-10 improved the crosstalk between NK cells and Kupffer cells. CONCLUSIONS Our findings in mice are the first to suggest the involvement of the NKG2D/RAE-1 interaction and cytokines in the synergistic effects of NK and Kupffer cells in PBC.

Concomitant methicillin-resistant Staphylococcus aureus infection in tubercular sacroiliitis masquerading as anti-tubercular drug resistance: Role for molecular diagnosis.

A 23-year-old female on anti-tubercular therapy for tuberculous sacroiliitis presented with right sided gluteal and thigh abscess. Suspecting treatment failure, surgical evacuation of purulent material was done. The bacteriological isolation showed positivity for methicillin-resistant Staphylococcus aureus. Although the microbiological and histopathology examination of the specimen were negative for tubercular isolates, the cartridge based -nucleic acid amplification tests revealed positive genes for Mycobacterium tuberculosis and additional primers showed sensitivity for rifampicin and isoniazid. She was adequately treated with vancomycin for six weeks and anti-tubercular drugs for eight months and followed till the bony ankyloses at 18 months. This is a rare case based scenario wherein concomitant staphylococcal infection in tubercular sacroiliitis masqueraded as anti-tubercular drug resistance. The cartridge-based nucleic acid amplification test for tuberculosis is a rapid and sensitive modality in identifying mycobacteria even mixed infections and also determine drug resistance. There are fewer consensuses in the literature regarding the drugs and duration of anti-tubercular regime for tuberculous sacroiliitis with most regimes using four drugs between six to eighteen months.

Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications.

Magnetic nanoparticles with appropriate surface coatings are increasingly being used clinically for various biomedical applications, such as magnetic resonance imaging, hyperthermia, drug delivery, tissue repair, cell and tissue targeting and transfection. This is because of the nontoxicity and biocompatibility demand that mainly iron oxide-based materials are predominantly used, despite some attempts to develop 'more magnetic nanomaterials' based on cobalt, nickel, gadolinium and other compounds. For all these applications, the material used for surface coating of the magnetic particles must not only be nontoxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. Magnetic nanoparticles can bind to drugs and an external magnetic field can be applied to trap them in the target site. By attaching the targeting molecules, such as proteins or antibodies, at particles surfaces, the latter may be directed to any cell, tissue or tumor in the body. In this review, different polymers/molecules that can be used for nanoparticle coating to stabilize the suspensions of magnetic nanoparticles under in vitro and in vivo situations are discussed. Some selected proteins/targeting ligands that could be used for derivatizing magnetic nanoparticles are also explored. We have reviewed the various biomedical applications with some of the most recent uses of magnetic nanoparticles for early detection of cancer, diabetes and atherosclerosis.

Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles.

The aim of this study was to modify the surfaces of superparamagnetic iron oxide nanoparticles (SPION) with pullulan in order to reduce the cytotoxicity and enhance the cellular uptake of the nanoparticles. In this study, we have prepared and characterised the pullulan coated superparamagnetic iron oxide nanoparticles (Pn-SPION) of size around 40-45 nm with magnetite inner core and hydrophilic outer shell of pullulan. We have investigated the effect of cellular uptake of uncoated and Pn-SPION on cell adhesion/viability, cytotoxicity, morphology and cytoskeleton organisation of human fibroblasts. Cell cytotoxicity/adhesion studies of SPIONs on human dermal fibroblasts showed that the particles are toxic and their internalisation resulted in disruption of cytoskeleton organisation of cells. On the other hand, Pn-SPIONs were found to be non-toxic and induced changes in cytoskeleton organisation different from that observed with SPION. Transmission electron microscopy results indicated that the SPION and Pn-SPION were internalised into cells via different mechanisms, thereby suggesting that the particle endocytosis behaviour is dependent on the surface characteristics of the nanoparticles.