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.

p62 Is a Potential Biomarker for Risk of Malignant Transformation of Oral Potentially Malignant Disorders (OPMDs).

To determine the intracellular behavior of p62, a marker of selective autophagy, in oral potentially malignant disorders (OPMDs). This retrospective study includes 70 patients who underwent biopsy or surgical resection and were definitively diagnosed with OPMDs. Immunohistochemical staining for p62, XPO1, p53, and ki67 was performed on all samples and positive cell occupancy was calculated. We statistically investigated the correlation between protein expression in OPMDs and the association between malignant transformation, clinicopathological characteristics, and occupancy. ki67 expression was negatively correlated with p62 expression in the nucleus (p < 0.01) and positively correlated with p62 expression in the cytoplasm (p < 0.01). For malignant transformation, the expression of p62 in the nucleus (p = 0.03) was significantly lower in malignant transformation cases, whereas the expression of p62 in the cytoplasm (p = 0.03) and the aggregation expression (p < 0.01) were significantly higher. Our results suggest that the function of p62 is altered by its subcellular localization. In addition, defects in selective autophagy occur in cases of malignant transformation, suggesting that p62 is a potential biomarker of the risk of malignant transformation of OPMDs.

A Case of Primary Intraosseous Adenoid Cystic Carcinoma of the Mandible.

Primary intraosseous adenoid cystic carcinoma (PIACC) of the jaw is rare. To our knowledge, only 51 cases have been reported in the English literature. We present a rare case of PIACC arising in the mandible with multiple bone metastases and review the previous articles. A 70-year-old woman presented with paresthesia of the right chin and lower gingiva for 4 months. Radiography revealed an irregular radiolucent region on the right side of the ramus, infiltrating to the mandibular canal. Biopsy revealed a pathological diagnosis of adenoid cystic carcinoma. Multiple bone metastases were present in the sternum, scapula, and thighs. The treatment effect was progressive disease for chemotherapy; therefore, best supportive care was provided for 3 years.

Heat-Killed Levilactobacillus brevis as a Candidate Postbiotics Through Immunostimulation Mediated by Macrophage-Inducible C-Type Lectin.

To understand the beneficial health-promoting effects of lactic acid bacteria (LAB) on immune cells, it is necessary to understand the relationship between LAB and innate immune receptors. We investigated the possible involvement of C-type lectin receptors (CLRs) in the immune-stimulating function of LAB in several strains. We found that levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 were reduced by the addition of inhibitors for spleen tyrosine kinase (syk), a signaling molecule used by several CLRs. Furthermore, employing CLR-Fc fusion proteins and reporter cells, we found that macrophage-inducible C-type lectin (Mincle) binds to Levilactobacillus brevis strain La37. Interestingly, this interaction was only observed in heat-killed L. brevis and disappeared after proteinase K treatment. Seven strains of L. brevis from different sources were also examined; among them, six strains showed Mincle reactivity, and the characteristics of the ligand were similar to those of La37. These results may facilitate a better understanding of the immunomodulatory effects of LAB for the development of functional foods.

Intravenous injection of mesenchymal stem cell spheroids improves the pulmonary delivery and prolongs in vivo survival.

BACKGROUND: Because of the excellent therapeutic potential, mesenchymal stem cells (MSCs) have been used as cell therapeutics for various diseases. However, the survival rate and duration of MSCs after transplantation are extremely low and short, respectively. To solve these problems, in this study, we prepared multicellular spheroids of MSCs and investigated their survival and function after intravenous injection in mice. METHODS AND RESULTS: The murine adipose-derived MSC line m17.ASC was cultured in agarose-based microwell plates to obtain size-controlled m17.ASC spheroids of an average diameter and cell number of approximately 170 µm and 1100 cells/spheroid, respectively. The intravenously injected m17.ASC spheroids mainly accumulated in the lung and showed a higher survival rate than suspended m17.ASC cells during the experimental period of 7 days. m17.ASC spheroids efficiently reduced the lipopolysaccharide-induced increase in plasma concentrations of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: These results indicate that spheroid formation improved the pulmonary delivery and survival of MSCs, as well as their therapeutic potential against inflammatory pulmonary diseases.

Convenient Decision Criteria for Surgery in Elderly Patients with Oral Squamous Cell Carcinoma.

Elderly patients with oral squamous cell carcinoma (OSCC) have difficulty undergoing curative surgical treatment due to various factors besides age. The purpose of the present study was to study the factors determining surgery in elderly patients with OSCC. We designed and implemented a retrospective cohort study. The study sample included elderly patients aged ≥ 70 years with OSCC and they were statistically compared between the surgery and non-surgery groups. The primary outcome variable was selecting surgery as the treatment plan, while the secondary outcome was the prognosis of each group. The sample comprised 76 patients aged ≥ 70 years with OSCC, of whom 52 treated with surgery and 24 patients treated with non-surgery. As decision factors, performance status (PS), clinical stage, serum Alb level, body mass index (BMI), and Geriatric Nutritional Risk Index (GNRI) were significantly associated with the selection of surgery. Logistic multivariate analysis identified three independent predictive factors for selecting surgery: Alb (≥3.5 vs. <3.5), PS (0, 1, 2, 3), and clinical stage. According to the decision tree analysis, curative surgery is the recommended treatment strategy for elderly patients with Alb ≥ 3.5 g/dL, PS 0, and stage I, II. In conclusion, Alb, PS, and clinical stage may be the criteria for selecting surgery in elderly patients.