There is much recent research interest in the molecular characteristics of cell-free DNA (cf DNA) in plasma. One such characteristic is the fragmentation patterns of cfDNA, including information regarding fragment sizes (1), nucleosome relationships (2, 3), and end points (4, 5). This area of research can be broadly named "fragmentomics" (6). cfDNA molecules are known to circulate as short fragments (1, 7) originating from different cell types, including various normal organ systems aBstRact Plasma DNA fragmentomics is an emerging area of research covering plasma DNA sizes, end points, and nucleosome footprints. In the present study, we found a significant increase in the diversity of plasma DNA end motifs in patients with hepatocellular carcinoma (HCC). Compared with patients without HCC, patients with HCC showed a preferential pattern of 4-mer end motifs. In particular, the abundance of plasma DNA motif CCCA was much lower in patients with HCC than in subjects without HCC. The aberrant end motifs were also observed in patients with other cancer types, including colorectal cancer, lung cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. We further observed that the profile of plasma DNA end motifs originating from the same organ, such as the liver, placenta, and hematopoietic cells, generally clustered together. The profile of end motifs may therefore serve as a class of biomarkers for liquid biopsy in oncology, noninvasive prenatal testing, and transplantation monitoring. SIGNIFICANCE: Plasma DNA molecules originating from the liver, HCC and other cancers, placenta, and hematopoietic cells each harbor a set of characteristic plasma DNA end motifs. Such markers carry tissueof-origin information and represent a new class of biomarkers in the nascent field of fragmentomics. Research.
Human serum albumin (HSA) is widely used in clinical and cell culture applications. Conventional production of HSA from human blood is limited by the availability of blood donation and the high risk of viral transmission from donors. Here, we report the production of
Oryza sativa
recombinant HSA (OsrHSA) from transgenic rice seeds. The level of OsrHSA reached 10.58% of the total soluble protein of the rice grain. Large-scale production of OsrHSA generated protein with a purity >99% and a productivity rate of 2.75 g/kg brown rice. Physical and biochemical characterization of OsrHSA revealed it to be equivalent to plasma-derived HSA (pHSA). The efficiency of OsrHSA in promoting cell growth and treating liver cirrhosis in rats was similar to that of pHSA. Furthermore, OsrHSA displays similar in vitro and in vivo immunogenicity as pHSA. Our results suggest that a rice seed bioreactor produces cost-effective recombinant HSA that is safe and can help to satisfy an increasing worldwide demand for human serum albumin.
Microalgae, a naturally present unicellular microorganism, can undergo light photosynthesis and have been used in biofuels, nutrition, etc. Here, we report that engineered live microalgae can be delivered to hypoxic tumor regions to increase local oxygen levels and resensitize resistant cancer cells to both radio- and phototherapies. We demonstrate that the hypoxic environment in tumors is markedly improved by in situ–generated oxygen through microalgae-mediated photosynthesis, resulting in notably radiotherapeutic efficacy. Furthermore, the chlorophyll from microalgae produces reactive oxygen species during laser irradiation, further augmenting the photosensitizing effect and enhancing tumor cell apoptosis. Thus, the sequential combination of oxygen-generating algae system with radio- and phototherapies has the potential to create an innovative treatment strategy to improve the outcome of cancer management. Together, our findings demonstrate a novel approach that leverages the products of photosynthesis for treatment of tumors and provide proof-of-concept evidence for future development of algae-enhanced radio- and photodynamic therapy.
Chronic nonhealing
wounds have imposed serious challenges in the clinical practice, especially
for the patients infected with multidrug-resistant microbes. Herein,
we developed an ultrasmall copper sulfide (covellite) nanodots (CuS
NDs) based dual functional nanosystem to cure multidrug-resistant
bacteria-infected chronic nonhealing wound. The nanosystem could eradicate
multidrug-resistant bacteria and expedite wound healing simultaneously
owing to the photothermal effect and remote control of copper-ion
release. The antibacterial results indicated that the combination
treatment of photothermal CuS NDs with photothermal effect initiated
a strong antibacterial effect for drug-resistant pathogens including
methicillin-resistant
Staphylococcus aureus
(MRSA) and extended-spectrum β-lactamase
Escherichia
coli
both in vitro and in vivo. Meanwhile, the released
Cu
2+
could promote fibroblast cell migration and endothelial
cell angiogenesis, thus accelerating wound-healing effects. In MRSA-infected
diabetic mice model, the nanosystem exhibited synergistic wound healing
effect of infectious wounds in vivo and demonstrated negligible toxicity
and nonspecific damage to major organs. The combination of ultrasmall
CuS NDs with photothermal therapy displayed enhanced therapeutic efficacy
for chronic nonhealing wound in multidrug-resistant bacterial infections,
which may represent a promising class of antibacterial strategy for
clinical translation.
Due to the inability
to spontaneously heal and vulnerability to
bacterial infection, diabetic patients are frustrated by unexpected
epithelium injuries in daily life. Notably, a drug-resistant bacterial
infection may result in a long-term impact to the natural function
of damaged organs. It is imperative to develop strategies that promote
injury recovery and eradicate drug-resistant infection simultaneously.
Here, we present a composite structured cupriferous hollow nanoshell
(AuAgCu2O NS) that consists of a hollow gold–silver
(AuAg) core and Cu2O shell as a photothermal therapeutic
agent for a cutaneous chronic wound and nonhealing keratitis with
drug-resistant bacterial infection. The controllable photothermal
therapeutic effect and released silver ion from the hollow AuAg core
possess a synergistic effect to eradicate multi-drug-resistant bacteria,
including extended-spectrum β-lactamase Escherichia
coli (ESBL E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Meanwhile, the released
copper ion from the Cu2O shell could expedite endothelial
cell angiogenesis and fibroblast cell migration, thus boosting wound-healing
effects. In both infection-complicated disease models, the ophthalmic
clinical score, wound closure rates, and histopathology analysis demonstrate
that the AuAgCu2O NSs could facilitate the re-epithelialization
at the wound area and eliminate the complicated bacterial infection
from diabetic mice. A primary signal path involved in the promoted
healing effect was further illustrated by comprehensive assays of
immunohistochemical evaluation, Western blot, and quantitative polymerase
chain reaction. Taken together, our AuAgCu2O NSs are shown
to be potent candidates for clinical utilization in the treatment
of diabetic epithelium injuries.
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