Maternal Th17/Treg Cytokines and Small Extracellular Vesicles in Plasma as Potential Biomarkers for Preeclampsia

Preeclampsia is one of the most serious pregnancy complications. It may be caused by immunological changes in the early placental microenvironment. The contents of small EVs may serve as biomarkers of pregnancy complications. Evidence suggests that the balance between T helper 17 (Th17) and regulatory T (Treg) cells are critical for preventing preeclampsia. The study recruited 39 pregnant women with preeclampsia and 127 healthy pregnant women. We assessed the levels of both Th17 and Treg cytokines (IL-10, IL-17, IL-21, IL-22, and TGF-β) in their plasma and small EVs. We found significant differences in the levels of all cytokines in the plasma between the two groups during the second trimester. We also observed significant differences between the two groups in the levels of EV-encapsulated cytokines IL-21, IL-22, and TGF-β, as well as in total small EVs, during the second trimester. The ROC analysis showed that the classification efficiency (AUC) of TGF-β in small EVs was 0.81. TGF-β had the best discriminant ability of all the single EV biomarkers tested, the cross-validation of the accuracy was 0.89. Th17 and Treg cytokines in plasma and small EVs may contribute to maternal immune activation and clarify the potential mechanisms of small EVs and cytokines in preeclampsia.     

Free-water diffusion MRI detects structural alterations surrounding white matter hyperintensities in the early stage of cerebral small vessel disease

In cerebral small vessel disease (CSVD), both white matter hyperintensities (WMH) of presumed vascular origin and the normal-appearing white matter (NAWM) contain microstructural brain alterations on diffusion-weighted MRI (DWI). Contamination of DWI-derived metrics by extracellular free-water can be corrected with free-water (FW) imaging. We investigated the alterations in FW and FW-corrected fractional anisotropy (FA-t) in WMH and surrounding tissue and their association with cerebrovascular risk factors. We analysed 1,000 MRI datasets from the Hamburg City Health Study. DWI was used to generate FW and FA-t maps. WMH masks were segmented on FLAIR and T1-weighted MRI and dilated repeatedly to create 8 NAWM masks representing increasing distance from WMH. Linear models were applied to compare FW and FA-t across WMH and NAWM masks and in association with cerebrovascular risk. Median age was 64 ± 14 years. FW and FA-t were altered 8 mm and 12 mm beyond WMH, respectively. Smoking was significantly associated with FW in NAWM (p = 0.008) and FA-t in WMH (p = 0.008) and in NAWM (p = 0.003) while diabetes and hypertension were not. Further research is necessary to examine whether FW and FA-t alterations in NAWM are predictors for developing WMH.     

Small GTPase—A Key Role in Host Cell for Coronavirus Infection and a Potential Target for Coronavirus Vaccine Adjuvant Discovery

Small GTPases are signaling molecules in regulating key cellular processes (e.g., cell differentiation, proliferation, and motility) as well as subcellular events (e.g., vesicle trafficking), making them key participants, especially in a great array of coronavirus infection processes. In this review, we discuss the role of small GTPases in the coronavirus life cycle, especially pre-entry, endocytosis, intracellular traffic, replication, and egress from the host cell. Furthermore, we also suggest the molecules that have potent adjuvant activity by targeting small GTPases. These studies provide deep insights and references to understand the pathogenesis of coronavirus as well as to propose the potential of small GTPases as targets for adjuvant development.     

A pilot study of intraoperative localization of peripheral small pulmonary tumors by cone-beam computed tomography: sandwich marking technique

BackgroundIntraoperative identification of small pulmonary nodules has been an important technical issue. We aimed to develop a new localization method which is much safer and simple procedure compared with conventional methods.MethodsThis was a retrospective study including patients with resected peripheral pulmonary nodules between November 2017 and April 2021 at Teikyo University School of Medicine, and Saitama Cardiovascular and Respiratory Center. All surgical procedure was wedge resection, and the tumor size was equal to or less than 20 mm which were detected by cone-beam computed tomography (CBCT; Philips Allura Xper FD 20, Philips). Some metal clips were put on several places of visceral pleura, where the target lesion was sandwiched by marking clips (sandwich marking technique). CBCT detected both the target lesion and metal clips, and video-assisted thoracoscopic surgery (VATS) was performed. Radiological and pathological findings were analyzed, and the correlation coefficient of tumor size was examined among pre-, intra-, and post-operative tumor sizes.ResultsThe average age of 90 patients was 65.2 years, and 47 were male (52.2%). All procedure was wedge resection including twelve bi-wedge resections, and one hundred nine peripheral pulmonary lesions were obtained by sandwich marking technique. The detection rate was 100%, and there was no marking-related complication.ConclusionsAll small peripheral pulmonary lesions were successfully detected and resected by using CBCT with no marking-related complication. Sandwich marking technique was demonstrated to provide safe, reliable, and simple localization procedure for small peripheral pulmonary lesions.     

Small extracellular vesicle-associated miR-6068 promotes aggressive phenotypes of prostate cancer through miR-6068/HIC2/SIRT1 axis

Early diagnosis and treatment of patients with aggressive prostate cancer (PCa) remains a clinically unmet need. We aimed to determine the levels of small extracellular vesicle (sEV)-associated microRNAs (miRs); miR-4737, miR-6068, and miR-6076 in a large panel of PCa cells and delineate the biological significance of miR-6068 in promoting PCa cells. sEVs were isolated from the conditioned medium of PCa cells, followed by RNA extraction and quantitative Real-Time PCR analysis. Functional assays were performed, and the protein expression of hypermethylated in cancer 2 (HIC2), as a potential miR-6068 target gene, was evaluated in PCa tissues by immunohistochemistry. sEV-associated miR-6068, miR-4737, and miR-6076 levels displayed large and significant differences compared to normal cells. miR-6068 was explicitly upregulated in sEV of PC-3 and CWR-R1ca cells (P<0.010). Suppression of miR-6068 in CWR-R1ca cells decreased cell proliferation, colony formation, and cell migration. In contrast, upregulation of miR-6068 in RC77T/E cells decreased HIC2 levels and increased cell aggressive phenotypes. The overexpression of HIC2 in PCa tissues was primarily observed in the cytoplasm compared to benign prostatic hyperplasia (BPH) and normal tissues (P<0.0001). This study confirms the differential packaging of miR-4737, miR-6068, and miR-6076 in sEVs of PCa cells. MiR-6068 promotes PCa cells to acquire aggressive phenotypes by inhibiting the HIC2/Sirtuin 1 (SIRT1) axis.     

Lower Rate of Water Absorption of an Oral Rehydration Solution with Partially Hydrolyzed Guar Gum in Conscious Rats

The purpose of the present study was to elucidate the rate of water absorption of an oral rehydration solution containing partially hydrolyzed guar gum (PHGG) in the small intestine, which is the main site of water absorption when water is drunk. Seven-week-old male SD rats were employed. We prepared four types of an aqueous solution, i.e., containing mineral and sugar, containing PHGG, containing mineral and sugar and PHGG, or containing no additives. After 24 h of food and 4 h of water deprivation, the aqueous solutions were infused into the stomach of conscious rats on their hands using a syringe with a stomach sonde. We sampled the stomach and the small intestine with contents 8 min after the infusions. Causal effects were calculated using a Bayesian network. PHGG increased the residual amount of water in the gastro-intestine, which depends negatively on the absorption of water in the small intestine/the flow rate to the small intestine. The absorption of water in the small intestine depended positively on the flow rate to the small intestine, which depended negatively on the free water in the solutions. PHGG decreased water absorption in the small intestine by decreasing the free water in the aqueous solutions.     

An outbreak of cryptosporidiosis associated with drinking water in north-eastern Italy,August 2019: microbiological and environmental investigations

Cryptosporidium is a leading global cause of waterborne disease, with many reported outbreaks related to main water supplies. In August 2019, an outbreak of cryptosporidiosis involving 80 cases occurred among 114 vacationers in a small municipality located in the Tuscan-Emilian Apennines, north-eastern Italy. After excluding a potential food-borne outbreak, the epidemiological investigation focussed on the hypothesis of a waterborne outbreak. This was confirmed by the finding of Cryptosporidium oocysts in stools of the cases and in water samples from the municipal water network. Molecular characterisation revealed the zoonotic species Cryptosporidium parvum as the causative agent. A single subtype (IIdA25G1) was found among all cases, and in one of two positive water samples. The municipality’s water supply used spring water that only received a disinfection treatment insufficient to inactivate the parasite. Possible entry means into the water mains were found through further environmental investigations. As these types of water supplies are particularly vulnerable to various environmental factors, a control system based on the risk assessment of each phase of the water supply chain is required to guarantee water safety. Effective methods for detection of protozoan pathogens, which are generally excluded from routine water supply analysis, should be applied.