Functional assessment of miR­1291 in colon cancer cells.

miR­1291 exerts an anti­tumor effect in a subset of human carcinomas, including pancreatic cancer. However, its role in colorectal cancer (CRC) is largely unknown. In the present study, the expression and effect of miR­1291 in CRC cells was investigated. It was identified that miR­1291 significantly suppressed the proliferation, invasion, cell mobility and colony formation of CRC cells. Additionally, miR­1291 induced cell apoptosis. A luciferase reporter assay revealed that miR­1291 directly bound the 3'­untranslated region sequence of doublecortin­like kinase 1 (DCLK1). miR­1291 also suppressed DCLK1 mRNA and protein expression in HCT116 cells that expressed DCLK1. Furthermore, miR­1291 suppressed cancer stem cell markers BMI1 and CD133, and inhibited sphere formation. The inhibitory effects on sphere formation, invasion and mobility in HCT116 cells were also explored and verified using DCLK1 siRNAs. Furthermore, miR­1291 induced CDK inhibitors p21WAF1/CIP1 and p27KIP1 in three CRC cell lines, and the overexpression of DCLK1 in HCT116 cells led to a decrease of p21WAF1/CIP1 and p27KIP1. Intravenous administration of miR­1291 loaded on the super carbonate apatite delivery system significantly inhibited tumor growth in the DLD­1 xenograft mouse model. Additionally, the resultant tumors exhibited significant upregulation of the p21WAF1/CIP1 and p27KIP1 protein with treatment of miR­1291. Taken together, the results indicated that miR­1291 served an anti­tumor effect by modulating multiple functions, including cancer stemness and cell cycle regulation. The current data suggested that miR­1291 may be a promising nucleic acid medicine against CRC.

[Transmission of SARS-CoV-2 through contact with a SARS-CoV-2-infected individual in the presymptomatic or asymptomatic state in Japan: A case series].

Objectives　There is little evidence supporting the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from presymptomatic or asymptomatic SARS-CoV-2-infected individuals in Japan, where the incidence of SARS-CoV-2 infection is lower than that in other developed countries. This study aimed to determine whether SARS-CoV-2 transmission can occur from presymptomatic or asymptomatic SARS-CoV-2-infected individuals.Methods　We surveyed all directors of Japanese public health centers for index cases and secondary patients who possibly contracted SARS-CoV-2 infection from a presymptomatic or asymptomatic SARS-CoV-2-infected individual who came under their care before June 20, 2020. The professional staff at the centers routinely perform contact tracing of infected persons based on the guidelines of the Infection Control Act. Four authors independently reviewed reports of 9 index cases of SARS-CoV-2-infected individuals with 17 secondary patients from 8 prefectures and examined the cases to determine whether transmission from a SARS-CoV-2-infected individual in the presymptomatic or asymptomatic state occurred.Results　We reported 7 index cases with 13 secondary patients. 1) An elderly woman acquired SARS-CoV-2 infection from her sustained asymptomatic granddaughter at home, 2) 4 guests and 1 accompanying child waiting at a hair salon acquired infection from the presymptomatic female hair stylist, 3) 2 inpatients acquired infection from a presymptomatic nurse while providing nursing care in close contact, 4) an elderly couple acquired SARS-CoV-2 infection from their presymptomatic relative who was in the 50s during household care at their home, 5) a man acquired SARS-CoV-2 infection from a presymptomatic adult neighbor in an enclosed space with poor ventilation, 6) a presymptomatic man had transmitted infection to another man at a coffee shop while having a discussion on business, and 7) a man in his 50s acquired SARS-CoV-2 infection from a presymptomatic man during 50 minutes of close contact at their office and in a car. These secondary patients had no other likely routes of infection. The interval between the date of symptom onset in the presymptomatic index case and the secondary patient ranged from 2 to 6 days. The incidence rates at the time these infections occurred in the corresponding prefectures ranged from 0.00 to 6.56 cases/1 million person-days.Conclusion　We report the first case of SARS-CoV-2 transmission from a sustained asymptomatic index case in Japan. All secondary patients came into close contact with presymptomatic index cases in areas with poor ventilation.

Gastrointestinal endoscopy in the era of the acute pandemic of coronavirus disease 2019: Recommendations by Japan Gastroenterological Endoscopy Society (Issued on April 9th, 2020).

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID-19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID-19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID-19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID-19; (ii) practical protective equipment for medical personnel depending on the risk for COVID-19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow-up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID-19.

Clinical Questions and Answers on Gastrointestinal Endoscopy during the Novel Coronavirus Disease 2019 pandemic.

Some situations may require endoscopy during the COVID-19 (Coronavirus Disease 2019) pandemic. Here, we describe the necessary precautions in the form of clinical questions and answers (Q&A) regarding the safe deployment of gastrointestinal endoscopy in such situations while protecting endoscopy staff and patients from infection. Non-urgent endoscopy should be postponed. The risk of infection in patients should be evaluated in advance by questionnaire and body temperature. The health of staff must be checked every day. Decisions to employ endoscopy should be based on the institutional conditions and aims of endoscopy. All endoscopic staff need to wear appropriate personal protective equipment (PPE). The endoscope and other devices should be cleaned and disinfected after procedures in accordance with the relevant guidelines. Optimal management of the endoscopy unit is required. Endoscopy for infected patients or those with suspected infection demands exceptional caution. When a patient who undergoes endoscopy is later found to have COVID-19, the members of staff involved are considered exposed to the virus and must not work for at least 14 days if their PPE is considered insufficient. When PPE resources are limited, some equipment may be used continuously throughout a shift as long as it is not contaminated. Details of the aforementioned protective measures are described.