Refractory acute graft-versus-host disease (aGVHD) is a major cause of death after allogeneic hematopoietic stem cell transplantation. This study evaluated the immunomodulation effects of mesenchymal stromal cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. Forty-seven patients with refractory aGVHD were enrolled: 28 patients receiving MSC and 19 patients without MSC treatment. MSCs were given at a median dose of 1 × 10(6) cells/kg weekly until patients got complete response or received 8 doses of MSCs. After 125 doses of MSCs were administered, with a median of 4 doses (range, 2 to 8) per patient, overall response rate was 75% in the MSC group compared with 42.1% in the non-MSC group (P = .023). The incidence of cytomegalovirus, Epstein-Barr virus infections, and tumor relapse was not different between the 2 groups during aGVHD treatment and follow-up. The incidence and severity of chronic GVHD in the MSC group were lower than those in the non-MSC group (P = .045 and P = .005). The ratio of CD3(+)CD4(+)/CD3(+)CD8(+) T cells, the frequencies of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), and the levels of signal joint T cell-receptor excision DNA circles (sjTRECs) after MSCs treatment were higher than those pretreatment. MSC-treated patients exhibited higher Tregs frequencies and sjTRECs levels than those in the non-MSC group at 8 and 12 weeks after treatment. MSCs derived from bone marrow of a third-party donor are effective to refractory aGVHD. It might reduce the incidence and severity of chronic GVHD in aGVHD patients by improving thymic function and induction of Tregs but not increase the risks of infections and tumor relapse.
Deep eutectic solvents (DESs) are a potentially high-value lignin extraction methodology. DESs prepared from choline chloride (ChCl) and three hydrogen-bond donors (HBD)—lactic acid (Lac), glycerol, and urea—were evaluated for isolation of willow (Salix matsudana cv. Zhuliu) lignin. DESs types, mole ratio of ChCl to HBD, extraction temperature, and time on the fractionated DES-lignin yield demonstrated that the optimal DES-lignin yield (91.8 wt % based on the initial lignin in willow) with high purity of 94.5% can be reached at a ChCl-to-Lac molar ratio of 1:10, extraction temperature of 120 °C, and time of 12 h. Fourier transform infrared spectroscopy (FT-IR) , 13C-NMR, and 31P-NMR showed that willow lignin extracted by ChCl-Lac was mainly composed of syringyl and guaiacyl units. Serendipitously, a majority of the glucan in willow was preserved after ChCl-Lac treatment.
A detailed
investigation of choline chloride-lactic acid (ChCl-LA)-based
deep eutectic solvent (DES) extraction of lignin nanoparticles from
herbaceous biomass (wheat straw) was conducted. It was found that
DES can extract high purity lignin (up to 94.8%) with a high yield
(up to 81.5% from air-dried samples and 85.9% from oven-dried samples)
from wheat straw. The cleavages of ether bonds in lignin, as well
as the linkages between lignin and hemicelluloses during DES treatments
at different conditions, were analyzed. The effects of reaction time,
treatment temperature and water content in wheat straw on lignin yield,
purity, and chemical structure were determined. The water content
in biomass was found to affect the hydrogen bond interaction between
lignin and DES, which was a key factor influencing the lignin extraction
yield and chemical properties of separated lignin. The lignin extracted
from wheat straw by DES consists of well-dispersed nanoparticles with
a narrow size distribution peaking at 70–90 nm. The mechanism
of ChCl-LA-based DES depolymerization and extraction of lignin from
wheat straw is discussed.
Glutathione S-transferase π (GSTπ) is a Phase II metabolic enzyme that is an important facilitator of cellular detoxification. Traditional dogma asserts that GSTπ functions to catalyze glutathione (GSH)-substrate conjunction to preserve the macromolecule upon exposure to oxidative stress, thus defending cells against various toxic compounds. Over the past 20 years, abnormal GSTπ expression has been linked to the occurrence of tumor resistance to chemotherapy drugs, demonstrating that this enzyme possesses functions beyond metabolism. This revelation reveals exciting possibilities in the realm of drug discovery, as GSTπ inhibitors and its prodrugs offer a feasible strategy in designing anticancer drugs with the primary purpose of reversing tumor resistance. In connection with the authors’ current research, we provide a review on the biological function of GSTπ and current developments in GSTπ-targeting drugs, as well as the prospects of future strategies.
Colorectal cancer (CRC) is frequently diagnosed at an advanced stage of the disease, the pathogenesis of which is influenced by genetic and epigenetic events. Circulating tumor DNA (ctDNA) is extracellular DNA that is present in a number of bodily fluids, including blood, synovial fluid and cerebrospinal fluid. Compared with performing a tissue biopsy, ctDNA examination presents the advantages of minimal invasion and greater convenience. ctDNA is commonly used to identify actionable genomic alterations, monitor treatment responses, unravel therapeutic resistance and potentially detect disease progression prior to clinical and radiological confirmation. The technique can potentially serve as a non-invasive diagnostic tool in personalized medicine, as it demonstrates prognostic value in the management of patients with CRC. ctDNA detection continues to demonstrate inherent advantages compared with other methods, thus serving an increasingly important role in tumor monitoring and oncotherapy. The aim of the current review was to explore the clinical applications of ctDNA in patients with CRC, including early detection and screening, medication guidance, resistance prediction, and residual lesion and recurrence monitoring. Furthermore, several technical methods for ctDNA detection and analysis are explored, as well as other potential biomarkers.
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