Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

New medical big data for P4 medicine on allergic conjunctivitis.

Allergic conjunctivitis affects approximately 15-20% of the global population and can permanently deteriorate one\u27s quality of life (QoL) and work productivity, leading to societal work force costs. Although not fully understood, allergic conjunctivitis is a multifactorial disease with a complex network of environmental, lifestyle, and host contributory risk factors. To effectively enhance the quality of treatment for patients with allergic conjunctivitis, as well as other allergic diseases, the field must first comprehend the pathology underlying various individualized subjective symptoms and stratify the disease according to risk factors and presentations. Such competent stratification and societal reconstruction that targets the alleviation of the damage due to allergic diseases would greatly help ramify personalized treatments and prevent the projected increase in societal costs imposed by allergic diseases. Owing to the rapid advancements in the information and technology sector, medical big data are greatly accessible and useful to decipher the pathophysiology of many diseases. Such data collected through multi-omics and mobile health have been effective for research on chronic diseases including allergic and immune-mediated diseases. Novel big data containing vast and continuous information on individuals with allergic conjunctivitis and other allergic symptoms are being used to search for causative genes of diseases, gain insights into new biomarkers, prevent disease progression, and, ultimately, improve QoL. The individualized and holistic data accrued from new angles using technological innovations are helping the field realize the principles of P4 medicine: predictive, preventive, personalized, and participatory medicine

Idiopathic Adult Intussusception : A Case Report

Adult intussusceptions account for 5-10％ of all intussusception cases and are considered rare, whereas they are most commonly encountered in children. Among adult cases, idiopathic intussusceptions are pretty rare. A 36-year-old male was admitted to our hospital with abdominal pain. His body temperature was 37.0℃, the white blood cell count was 14,000/μl and CRP 0.01mg/dl. A standing abdominal X-ray showed slight niveau formation. Computed tomography demonstrated the multiple concentric ring sign. His condition detoriorated and a laparotomy was performed. Intraoperatlvely,a mass measuring six centimeters in diameter was seen in the left side of the hepatic flexure of the transverse colon. The diseased intestine was reducted with Hutchinson’s maneuver. No lesions or malignancy were found, however an ileocecal resection was performed to prevent recurrence of the intussusception. The resected specimen showed congestion and wall thickening. Pathological examination of resected specimen showed marked congestion and hemorrhage with coagulation necrosis. The patient’s postoperative course was uneventful and he was discharged from our hospital on the 10th postoperative day. After nineteen months’follow up,no recurrence of the intussusception has been seen. Reduction of the bowel followed by minimum bowel resection should be considered to prevent recurrence of the intussusception and to avoid short gut or adhesional ileus

Malignant Lymphoma of the Ileum Treated by Laparoscopically Assisted Bowel Resection : A Case Report

Primary malignant lymphoma of the small intestine is uncommon. We herein present a case of malignant lymphoma of the ileum, which was treated by laparoscopically assisted surgery. A 60-yearold male with lower abdominal pain and vomiting was admitted to our hospital. A standing abdominal X-ray showed niveau formation. Computed tomography demonstrated circumferential wall thickening in the terminal ileum. Laparoscopically assisted surgery was performed under a diagnosis of tumor of the ileum. Under laparoscopic exploration, tumor of the ileum was detected. Partial resection of the ileum and dissection of lymph nodes were performed extracorporeally. Histological findings demonstrated diffuse large atypical lymphocytes with vesicle-like chromatin and clear nucleolus. Immunologically, CD20 and CD79a were positive. These findings were compatible with those of diffuse large B-cell lymphoma. Paraintestinal lymph nodes were also involved. The postoperative course was uneventful. Neither gallium scintigraphy nor FDG-PET showed any scintillation. The patient was given R-CHOP therapy and is currently doing well with no sign of recurrence. In conclusion, we propose that laparoscopic surgery for malignant lymphoma of the small intestine is a feasible and promising therapeutic option, especially in a case demonstrating bowel obstruction, because this procedure is thought to be minimally invasive,allows quick postoperative recovery and shortened hospital stay could be expected