Biological effects of anhydrobiosis in an African chironomid, Polypedilum vanderplanki on radiation tolerance

PURPOSE: Anhydrobiotic organisms are known to have an extremely high tolerance against a range of stresses. However, the functional role of anhydrobiosis in radiation tolerance is poorly understood, especially in development following irradiation. The present study aims to evaluate effects of anhydrobiosis on radiation tolerance in an anhydrobiotic insect, Polypedilum vanderplanki. MATERIALS AND METHODS: Larval survival (48 h), anhydrobiotic ability, metamorphosis and reproduction after exposure to 1-9000 Gy of gamma-rays at the larval stage were compared between anhydrobiotic (dry) and normal (wet) phases. RESULTS: Wet larvae were killed in a dose-dependent manner at doses higher than 2000 Gy, and all died within 8 h after 4000 Gy exposure. In contrast, dry larvae survived even 5000 Gy, and some of them still tolerated 7000 Gy and were alive at 48 h after rehydration. Moreover, greater radiotolerance of dry larva, compared to wet ones, was demonstrated in terms of metamorphoses. However, anhydrobiosis did not protect against radiation damage in terms of producing viable offspring. CONCLUSION: These results indicate that anhydrobiosis enhances radiotolerance, resulting in increases of successful metamorphoses.     

Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for this transformation remains unclear. Here, we explored the link between autophagic decline and cumulus transformation using cumulus cells from patients with infertility, female mice, and human granulosa cell-derived KGN cell lines. When human cumulus cells were labeled with LysoTracker probes, fluorescence corresponding to lysosomes was enhanced in DCCs compared to that in MCCs and ICCs. Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice. Electron microscopy analysis revealed the proliferation of abnormal lysosomes in chloroquine-treated KGN cells. Conversely, the addition of an autophagy inducer, trehalose, suppressed chloroquine-driven problematic lysosomal anomalies and ameliorated ovulation problems. Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility.     

Composite implantation of mesenchymal stem cells with endothelial progenitor cells enhances tissue-engineered bone formation

For successful tissue engineering, neovascularization of the implanted tissue is critical. Factors generated by endothelial cells are also considered crucial for the process of osteogenesis. The direct effects of supplementing tissue engineered constructs with cultured endothelial progenitor cells (EPCs) for enhancing bone regeneration have not been reported. In this study, we investigated the potential of EPCs to facilitate neovascularization in implants and evaluated their influence on bone regeneration. The influence of EPC soluble factors on osteogenic differentiation of mesenchymal stem cells (MSCs) was tested by adding EPC culture supernatant to MSC culture medium. To evaluate the influence of EPCs on MSC osteogenesis, canine MSCs-derived osteogenic cells and EPCs were seeded independently onto collagen fiber mesh scaffolds and co-transplanted to nude mice subcutaneously. Results from coimplant experiments were compared to implanted cells absent of EPCs 12 weeks after implantation. Factors from the culture supernatant of EPCs did not influence MSC differentiation. Coimplanted EPCs increased neovascularization and the capillary score was 1.6-fold higher as compared to the MSC only group (p < 0.05). Bone area was also greater in the MSC + EPC group (p < 0.05) and the bone thickness was 1.3-fold greater in the MSC + EPC group than the MSC only group (p < 0.05). These results suggest that soluble factors generated by EPCs may not facilitate the osteogenic differentiation of MSCs; however, newly formed vasculature may enhance regeneration of tissue-engineered bone.     

Prognostic value of cardiovascular magnetic resonance derived right ventricular function in patients with interstitial lung disease

Background

Cardiovascular magnetic resonance (CMR) provides non-invasive and more accurate assessment of right ventricular (RV) function in comparison to echocardiography. Recent study demonstrated that assessment of RV function by echocardiography was an independent predictor for mortality in patients with interstitial lung disease (ILD). The purpose of this study was to determine the prognostic significance of CMR derived RV ejection fraction (RVEF) in ILD patients.

Methods

We enrolled 76 patients with ILD and 24 controls in the current study. By using 1.5 T CMR scanner equipped with 32 channel cardiac coils, we performed steady-state free precession cine CMR to assess the RVEF. RV systolic dysfunction (RVSD) was defined as RVEF ≤45.0% calculated by long axis slices. Pulmonary hypertension (PH) was defined as mean pulmonary artery pressure (mPAP) of more than 25 mmHg at rest in the setting of pulmonary capillary wedge pressure ≤15 mmHg.

Results

The median RVEF was 59.2% in controls (n = 24), 53.8% in ILD patients without PH (n = 42) and 43.1% in ILD patients with PH (n = 13) (p < 0.001 by one-way ANOVA). During a mean follow-up of 386 days, 18 patients with RVSD had 11 severe events (3 deaths, 3 right heart failure, 3 exacerbation of dyspnea requiring oxygen, 2 pneumonia requiring hospitalization). In contrast, only 2 exacerbation of dyspnea requiring oxygen were observed in 58 patients without RVSD. Multivariate Cox regression analysis showed that RVEF independently predicted future events, after adjusting for age, sex and RVFAC by echocardiography (hazard ratio: 0.889, 95% confidence interval: 0.809 – 0.976, p = 0.014).

Conclusions

The current study demonstrated that RVSD in ILD patients can be clearly detected by cine CMR. Importantly, low prevalence of PH (17%) indicated that population included many mild ILD patients. CMR derived RVEF might be useful for the risk stratification and clinical management of ILD patients.     

Changes of the Intestinal Microbiota, Short Chain Fatty Acids, and Fecal pH in Patients with Colorectal Cancer

Background

New molecular biology-based methods of bacterial identification are expected to help elucidate the relationship between colorectal cancer (CRC) and intestinal microbiota. Although there is increasing evidence revealing the potential role of microbiota in CRC, it remains unclear whether microbial dysbiosis is the cause or the result of CRC onset.

Aim

We investigated the changes of intestinal environments in CRC or adenoma.

Methods

We analyzed 13 groups of microbiota, 8 types of organic acids, and pH in feces obtained from the following 3 groups: individuals with CRC, adenoma, and non-adenoma. Ninety-three patients with CRC and 49 healthy individuals (22 with adenoma and 27 without adenoma) were enrolled.

Results

The counts of total bacteria (10.3 ± 0.7 vs. 10.8 ± 0.3 log₁₀ cells/g of feces; p < 0.001), 5 groups of obligate anaerobe, and 2 groups of facultative anaerobes were significantly lower in the CRC group than in the healthy individuals. While the concentrations of short chain fatty acids (SCFAs) were significantly decreased in the CRC group, the pH was increased in the CRC group (7.4 ± 0.8 vs. 6.9 ± 0.6; p < 0.001). Comparison among the CRC, adenoma, and non-adenoma groups revealed that fecal SCFAs and pH in the adenoma group were intermediate to the CRC group and the non-adenoma group. Within the CRC group, no differences in microbiota or organic acids were observed among Dukes stages.

Conclusions

CRC patients showed significant differences in the intestinal environment, including alterations of microbiota, decreased SCFAs, and elevated pH. These changes are not a result of CRC progression but are involved in CRC onset.     

Rat‐bite fever identified by polymerase chain reaction detection of Streptobacillus moniliformis DNA

A 74‐year‐old woman presented with erythema of the extremities, a high fever and arthralgia after being bitten by a rat. The patient was diagnosed as having rat‐bite fever based on the symptoms and clinical course, as well as the polymerase chain reaction detection of Streptobacillus moniliformis DNA in the crust of the bite site. This is the first case to be diagnosed using polymerase chain reaction on a crusted skin lesion specimen. Although clinical symptoms initially remitted with minocycline therapy, they relapsed. Subsequent administration of piperacillin sodium resulted in complete disappearance of the high fever and arthralgia.     

A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice

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Evaluation of paramalleolar and inframalleolar bypasses in dialysis- and nondialysis-dependent patients with critical limb ischemia

Objective

The aim of this study was to elucidate the efficacy of paramalleolar or inframalleolar bypass (PIMB) in hemodialysis-dependent (HD) patients with critical limb ischemia (CLI) and nonhemodialysis-dependent (NHD) patients in terms of clinical outcomes.