Scutellaria Root extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content.

Scuellaria Root (SR, root of Scutellaria baicalensis), which has potent anti-inflammatory effects, is a component of useful Kampo formulae. Albeit a low frequency, SR induces serious interstitial pneumonia and liver dysfunction. In this study, to control the adverse effects of SR, we investigated the causal constituent responsible for its hepatocytotoxicity and aimed to develop a method to control it. As a result, we revealed that the hepatocytotoxicity of SR was correlated with its baicalin content, a major constituent in SR. It was confirmed by preparing a baicalin-free SR extract, which exhibited reduced hepatocytotoxicity. The addition of baicalin to the baicalin-free SR extract restored the hepatocytotoxicity, indicating that the hepatocytotoxicity of SR is dependent on its baicalin content. Thus, SR extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content.

Comparison of early wound healing using modified papilla preservation technique between enamel matrix derivative and recombinant human fibroblast growth factor.

PURPOSE: Enamel matrix derivative (EMD) has demonstrated beneficial effects on wound healing following surgery. However, the effects of recombinant human fibroblast growth factor 2 (rhFGF-2) in periodontal regeneration therapy have not been extensively studied. This retrospective study was conducted to compare the wound healing outcomes of the modified papilla preservation technique (mPPT) between EMD and rhFGF-2 therapies. METHODS: A total of 79 sites were evaluated for early wound healing using the modified early wound healing index (mEHI), which included 6 items: incision, fibrin clotting, step, redness, swelling, and dehiscence. A numeric analog scale, along with postoperative images of the 6 mEHI items, was established and used for the evaluations. The inter-rater reliability of the mEHI was assessed via intraclass correlation coefficients (ICCs). After adjusting for factors influencing the mPPT, the differences in mEHI scores between the EMD and rhFGF-2 groups were statistically analyzed. Additionally, radiographic bone fill (RBF) was evaluated 6 months after surgery. RESULTS: The ICC of the mEHI was 0.575. The mEHI, redness score, and dehiscence scores were significantly higher in the rhFGF-2 group (n=33) than in the EMD group (n=46). Similar results were observed in the subgroup of patients aged 50 years or older, but not in those younger than 50 years. In the subgroup with non-contained bone defects, related results were noted, but not in the subgroup with contained bone defects. However, early wound healing did not correlate with RBF at 6 months after surgery. CONCLUSIONS: Within the limitations of this study, the findings suggest that early wound healing following the use of mPPT with rhFGF-2 is somewhat superior to that observed after mPPT with EMD. However, mEHI should be improved for use as a predictive tool for early wound healing and to reflect clinical outcomes after surgery.

Impact of COVID-19 spread on visit intervals and clinical parameters for patients with periodontitis in supportive periodontal therapy: a retrospective study.

PURPOSE: This study investigated the relationship between the number of days that hospital visits were postponed and changes in clinical parameters due to the spread of coronavirus disease 2019 (COVID-19), after the Japanese government declared a state of emergency in April 2020. METHODS: Regarding the status of postponement of appointments, we analyzed the patients who had visited the Nihon University Hospital at Matsudo for more than 1 year for supportive periodontal therapy (SPT) and classified them into low-, moderate- and high-risk subgroups according to the periodontal risk assessment (PRA). Clinical parameters for periodontal disease such as probing depth (PD), full-mouth bleeding score (FMBS), full-mouth plaque score, periodontal inflamed surface area (PISA), and periodontal epithelial surface area (PESA) were analyzed in 2 periods, from October 2019 to March 2020 and after April 2020. Correlation coefficients between days of deferral and the degree of changes in clinical parameters were calculated. RESULTS: The mean age of the 749 patients was 67.56±10.85 years, and 63.82% were female. Out of 749 patients, 33.24% deferred their SPT appointments after April 2020. The average total of postponement days was 109.49±88.84. The number of postponement days was positively correlated with changes in average PD (rs=0.474) and PESA (rs=0.443) in the high-risk subgroup of FMBS, and average PD (rs=0.293) and PESA (rs=0.253) in the high-risk subgroup of tooth number (TN). Patients belonging to the high-risk subgroups for both FMBS and TN had a positive correlation between postponement days and PISA (rs=0.56). CONCLUSIONS: The findings, the spread of COVID-19 appears to have extended the visit interval for some SPT patients. Moreover, longer visit intervals were correlated with the worsening of some clinical parameters for SPT patients with high PRA.

Bronchiectasis and Bronchiolectasis With Severe Herniating Pattern Associated With STAT1 Gain-of-Function Mutation: Detailed Clinicopathological Findings.

STAT1 gain-of-function (GOF) mutations are associated with a rare autosomal dominant immunodeficiency disorder with main clinical manifestations including chronic mucocutaneous candidiasis (CMC) and bronchiectasis. In addition, these patients show higher incidences of cerebral and extracerebral aneurysm, malignancies and various autoimmune conditions compared to the general population. Although previous publications have reported clinical findings in patients with STAT1 GOF mutation, they did not include histopathologic features. Herein, we describe the first case with detailed histologic findings in the lung of a 5-year-old patient with a de novo STAT1 GOF mutation, who presented with CMC and bronchiectasis. The biopsy showed severe bronchiolectasis with extensive airway dilatation and occasional disruptions. Peribronchiolar inflammation was not always present and evident mainly in areas of airway disruption; inflammation may have not been a main driver of the airway damage in this case. The airway dilatation often showed an interesting herniating pattern, possibly implying a connective tissue etiology. This case also demonstrates the diagnostic utility of whole exome sequencing as STAT1 GOF mutations are not detected by routine workup. The definitive diagnosis will lead to more specific treatments and increased surveillance for serious conditions, such as cerebral aneurysms and malignancies.

Association of a de novo nonsense mutation of the TRIM8 gene with childhood-onset focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is an etiologically heterogeneous disorder. Genetic FSGS may be either limited to the kidney or part of a genetic syndrome with other systemic involvement. At least 21 and 34 genes have been reported for renal-limited and syndromic FSGS, respectively. The TRIM8 gene encodes a tripartite motif protein, which is an E3 ubiquitin-protein ligase that promotes proteasomal degradation of the suppressor of cytokine signaling 1 (SOCS1) and participates in the activation of interferon-gamma signaling. The TRIM8 gene is expressed in various tissues including the kidney and the central nervous system (CNS). An association between a mutation in the TRIM8 gene and childhood-onset FSGS has not been well established. CASE-DIAGNOSIS: We describe an 8-year-old Hispanic male with infantile onset motor and developmental delay, seizures, and proteinuria secondary to FSGS. Next generation sequencing revealed a heterozygous de novo pathogenic variant in the TRIM8 gene (C1380T>A, p.Tyr460*). Immunohistochemical staining using anti-TRIM8 and anti-SOCS1 antibodies showed no significant TRIM8 expression and strong expression of SOCS1 in the renal biopsy tissue. TREATMENT AND CONCLUSIONS: De novo truncating mutations of TRIM8 have been previously reported in childhood-onset epileptic encephalopathy. A molecular analysis of TRIM8 should be considered in children with FSGS and clinical abnormalities of the central nervous system.

A Complication of Percutaneous Sclerotherapy for Congenital Pulmonary Airway Malformation: Intravascular Injection and Cardiac Necrosis.

INTRODUCTION: A congenital pulmonary airway malformation (CPAM) type III may become large enough to cause hydrops fetalis. In such circumstances, the fetus can be treated with open fetal resection, maternal betamethasone administration, or percutaneous sclerotherapy. CASE REPORT: A 24 week gestation fetus with a CPAM type III was treated by percutaneous sclerotherapy using ethanolamine oleate (EO). The EO inadvertently entered the left atrium and ventricle with subsequent fetal bradycardia and demise. Autopsy revealed myocardial necrosis. CONCLUSION: Percutaneous sclerotherapy has been previously described in the literature for the treatment of microcystic CPAMs with secondary hydrops. This is the first reported case of an adverse event after fetal sclerotherapy.

TALEN-mediated mutagenesis in zebrafish reveals a role for r-spondin 2 in fin ray and vertebral development.

R-spondin (Rspo) encodes a multi-domain protein that modulates the Wnt-signaling pathway. Two distinct rspo2 zebrafish mutants were generated by TALEN-mediated mutagenesis: a null mutant, rspo2(null), lacking all functional domains, and a hypomorphic mutant, rspo2(tsp), lacking the two N-terminal domains. Mutants were analyzed mainly for abnormalities in the skeletal system. Fin ray skeletons were formed normally in the rspo2(tsp) mutants, but were absent from the rspo2(null) mutants. Hypoplasia of the neural/hemal arches and ribs was observed in both mutants. Thus, the two rspo2 mutants help to identify the functions of Rspo2 in skeletogenesis, as well as functional differences among multiple Rspo2 domains.

Side population cells from human melanoma tumors reveal diverse mechanisms for chemoresistance.

Side population (SP) cells are identified as cells capable of excluding the fluorescent Hoechst dye and anticancer drugs, and it represents hematopoietic stem cells and chemoresistant cells from several solid tumors. In this study, we confirmed the presence of SP cells in tumors from melanoma patients. Melanoma SP cells overexpressed ATP-binding-cassette (ABC) transporters, ABCB1 and ABCB5. We generated a direct in vivo xenograft model, and demonstrated that SP cells were resistant to paclitaxel, a substrate of ABCB1, both in vitro and in vivo. However, melanoma SP cells were also resistant to temozolomide, which is not a substrate for ABC transporters, through IL-8 upregulation. In addition, gene profiling studies identified three signaling pathways (NF-κB, α6-ß4-integrin, and IL-1) as differentially upregulated in melanoma SP cells, and there was a significant increase of PCDHB11 and decrease of FUK and TBX2 in these cells. Therefore, we provide evidence that SP is an enriched source of chemoresistant cells in human melanomas, and suggest that the selected genes and signaling pathways of SP cells may be a potential target for effective melanoma therapies. To our knowledge, this is a previously unreported study to isolate SP cells from melanoma patients and to investigate the gene expression profiling of these cells.