Severe radiation exposure may cause acute radiation syndrome, a possibly fatal condition requiring effective therapy. Gut microbiota can be manipulated to fight against many diseases. We explored whether intestinal microbe transplantation could alleviate radiation‐induced toxicity. High‐throughput sequencing showed that gastrointestinal bacterial community composition differed between male and female mice and was associated with susceptibility to radiation toxicity. Faecal microbiota transplantation (FMT) increased the survival rate of irradiated animals, elevated peripheral white blood cell counts and improved gastrointestinal tract function and intestinal epithelial integrity in irradiated male and female mice. FMT preserved the intestinal bacterial composition and retained mRNA and long non‐coding RNA expression profiles of host small intestines in a sex‐specific fashion. Despite promoting angiogenesis, sex‐matched FMT did not accelerate the proliferation of cancer cells in vivo. FMT might serve as a therapeutic to mitigate radiation‐induced toxicity and improve the prognosis of tumour patients after radiotherapy.

The molecular weight (MW) of a protein can be predicted based on its amino acids (AA) composition. However, in many cases a non-chemically modified protein shows an SDS PAGE-displayed MW larger than its predicted size. Some reports linked this fact to high content of acidic AA in the protein. However, the exact relationship between the acidic AA composition and the SDS PAGE-displayed MW is not established. Zebrafish nucleolar protein Def is composed of 753 AA and shows an SDS PAGE-displayed MW approximately 13 kDa larger than its predicted MW. The first 188 AA in Def is defined by a glutamate-rich region containing ~35.6% of acidic AA. In this report, we analyzed the relationship between the SDS PAGE-displayed MW of thirteen peptides derived from Def and the AA composition in each peptide. We found that the difference between the predicted and SDS PAGE-displayed MW showed a linear correlation with the percentage of acidic AA that fits the equation y = 276.5x − 31.33 (x represents the percentage of acidic AA, 11.4% ≤ x ≤ 51.1%; y represents the average ΔMW per AA). We demonstrated that this equation could be applied to predict the SDS PAGE-displayed MW for thirteen different natural acidic proteins.

Modern lifestyles, such as shift work, nocturnal social activities, and jet lag, disturb the circadian rhythm. The interaction between mammals and the co-evolved intestinal microbiota modulates host physiopathological processes. Radiotherapy is a cornerstone of modern management of malignancies; however, it was previously unknown whether circadian rhythm disorder impairs prognosis after radiotherapy. To investigate the effect of circadian rhythm on radiotherapy, C57BL/6 mice were housed in different dark/light cycles, and their intestinal bacterial compositions were compared using high throughput sequencing. The survival rate, body weight, and food intake of mice in diverse cohorts were measured following irradiation exposure. Finally, the enteric bacterial composition of irradiated mice that experienced different dark/light cycles was assessed using 16S RNA sequencing. Intriguingly, mice housed in aberrant light cycles harbored a reduction of observed intestinal bacterial species and shifts of gut bacterial composition compared with those of the mice kept under 12 h dark/12 h light cycles, resulting in a decrease of host radioresistance. Moreover, the alteration of enteric bacterial composition of mice in different groups was dissimilar. Our findings provide novel insights into the effects of biological clocks on the gut bacterial composition, and underpin that the circadian rhythm influences the prognosis of patients after radiotherapy in a preclinical setting.

Although radiation therapy is a cornerstone of modern management of malignancies, various side effects are inevitably linked to abdominal and pelvic cancer after radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life quality of cancer survivors and even shortens their lifespan. Hydrogen has been shown to protect against tissue injuries caused by oxidative stress and excessive inflammation, but its effect on radiation-induced intestinal injury was previously unknown. In the present study, we found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated with an improvement in GI tract function and the epithelial integrity of the small intestine. Mechanistically, microarray analysis revealed that hydrogen-water administration upregulated miR-1968-5p levels, thus resulting in parallel downregulation of MyD88 expression in the small intestine after TAI exposure. Additionally, high-throughput sequencing showed that hydrogen-water oral gavage resulted in retention of the TAI-shifted intestinal bacterial composition in mice. Collectively, our findings suggested that hydrogen-water might be used as a potential therapeutic to alleviate intestinal injury induced by radiotherapy for abdominal and pelvic cancer in preclinical settings.

Human embryonic stem cell (hESC) derived 3D human lung organoids (HLOs) provide a promising model to study human lung development and disease. HLOs containing proximal or/and immature distal airway epithelial cells have been successfully generated in vitro, such as early staged alveolar type 2 (AT2) cells (SPC/SOX9) and immature alveolar type 1 (AT1) cells (HOPX/SOX9). When HLOs were transplanted into immunocompromised mice for further differentiation in vivo, only few distal epithelial cells could be observed. In this study, we transplanted different stages of HLOs into immunocompromised mice to assess whether HLOs could expand and mature in vivo. We found that short-term transplanted HLOs contained lung progenitor cells (NKX2.1, SOX9, and P63), but not SPC AT2 cells or AQP5 AT1 cells. Meanwhile, long-term engrafted HLOs could differentiate into lung distal bipotent progenitor cells (PDPN/SPC/SOX9), AT2 cells (SPC, SPB), and immature AT1 cells (PDPN, AQP5). However, HLOs at late in vitro stage turned into mature AT1-like cells (AQP5/SPB/SOX9) in vivo. Immunofluorescence staining and transmission electron microscopy (TEM) results revealed that transplanted HLOs contained mesenchymal cells (collagen I), vasculature (ACTA2), neuroendocrine-like cells (PGP9.5), and nerve fiber structures (myelin sheath structure). Together, these data reveal that hESC-derived HLOs would be useful for human lung development modeling, and transplanted HLOs could mimic lung organ-like structures in vivo by possessing vascular network and neuronal network.

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Natural antisense transcripts (NATs), which are transcribed from opposite strands of DNA with partial or complete overlap, affect multiple stages of gene expression, from epigenetic to post-translational modifications. NATs are dysregulated in various types of cancer, and an increasing number of studies focusing on NATs as pivotal regulators of the hallmarks of cancer and as promising candidates for cancer therapy are just beginning to unravel the mystery. Here, we summarize the existing knowledge on NATs to highlight their underlying mechanisms of functions in cancer biology, discuss their potential roles in therapeutic application, and explore future research directions.

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