Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer.

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

Sweet Bee Venom Triggers Multiple Cell Death Pathways or Spurs Acute Cell Rupture According to Its Concentration in THP-1 Monocytic Leukemia Cells.

Sweet bee venom (sBV) contains various pharmacologically active components of bee venom (BV), but it is modified via the removal of the harmful substances found in BV. Thus, sBV has been used for pain relief in Oriental medicine but has only recently been applied for the treatment of various diseases. In this study, we examined the pharmacological effects and immunomodulatory functions of sBV in THP-1 monocytic leukemia cells. Growth inhibition and cell death were observed according to the concentration of sBV. However, the rapid collapse of cell cycle distribution was shown at 20 µg/mL sBV treatment, indicating that sBV led to cell death or acute cell rupture according to concentration. sBV administration activated Caspase-9, PARP1, RIPK1, and RIPK3, suggesting that the pharmacological actions of sBV were associated with induction of apoptosis and necroptosis. On the other hand, sBV or LPS administration increased cytokine expression, including IL-1ß, and showed synergistic cell death in combinatory treatment conditions. Moreover, combinatory administration of sBV and LPS induced severe damage or death during egg development. This result implies that sBV exhibits both pharmacological and toxic effects depending on its concentration. Therefore, sBV might be a promising therapeutic approach, but optimal concentration should be considered before treatment.

Regulatory Effect of Cannabidiol (CBD) on Decreased ß-Catenin Expression in Alopecia Models by Testosterone and PMA Treatment in Dermal Papilla Cells.

OBJECTIVES: The hair follicle is composed of more than 20 kinds of cells, and mesoderm derived dermal papilla cells and keratinocytes cooperatively contribute hair growth via Wnt/ß-catenin signaling pathway. We are to investigate ß-catenin expression and regulatory mechanism by CBD in alopecia hair tissues and dermal papilla cells. METHODS: We performed structural and anatomical analyses on alopecia patients derived hair tissues using microscopes. Pharmacological effect of CBD was evaluated by ß-catenin expression using RT-PCR and immunostaining experiment. RESULTS: Morphological deformation and loss of cell numbers in hair shaft were observed in alopecia hair tissues. IHC experiment showed that loss of ß-catenin expression was shown in inner shaft of the alopecia hair tissues, indicating that ß-catenin expression is a key regulatory function during alopecia progression. Consistently, ß-catenin expression was decreased in testosterone or PMA treated dermal papilla cells, suggesting that those treatments are referred as a model on molecular mechanism of alopecia using dermal papilla cells. RT-PCR and immunostaining experiments showed that ß-catenin expression was decreased in RNA level, as well as decreased ß-catenin protein might be resulted from ubiquitination. However, CBD treatment has no changes in gene expression including ß-catenin, but the decreased ß-catenin expression by testosterone or PMA was restored by CBD pretreatment, suggesting that potential regulatory effect on alopecia induction of testosterone and PMA. CONCLUSION: CBD might have a modulating function on alopecia caused by hormonal or excess of signaling pathway, and be a promising application for on alopecia treatment.

Identification of Cleaved Haptoglobin in the Serum of Bee Venom-Hypersensitive Patients.

Background: Bee venom has been used as a therapeutic compound for various human diseases in oriental medicine; however, it can induce anaphylaxis in hypersensitive patients during treatment. Anaphylaxis is an acute allergic reaction that occurs after allergen exposure. IgE is released from immune-related cells such as mast cells and basophils during anaphylaxis. Various inflammatory mediators are also released into the bloodstream during the acute response. Objectives: We aimed to identify specific proteins from bee venom-hypersensitive patients. Methods: We analyzed the blood serum of control and bee venom-hypersensitive patients using two-dimensional (2D) electrophoresis. Results: An interesting protein spot with a molecular size of 10 kDa was identified at an isoelectric point (p.I.) of 5.5. Spots detected both before and after sweet bee venom therapy were not proteins induced by sweet bee venom. The 10 kDa protein was identified as the cleaved form of haptoglobin through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Statistical analysis indicated that the presence of the spot was highly significant in the bee venom-hypersensitive group. Conclusion: The findings suggest that cleaved haptoglobin may be a significant diagnostic protein for anaphylaxis. In addition, a high incidence of bee venom hypersensitivity may be associated with the haptoglobin genotype.

A Literature Analysis on Medicinal Use and Research of Cannabis in the Meiji Era of Japan.

Cannabis is a historical plant which has been used as a medicine in East Asia. These days, there are active debates about using cannabis in clinical field. Collecting and comparing cannabis research articles which had been published in the Opening of Japan to spot the interactions between the traditional medicine of Japan, Rangaku which was established in Edo Period and the European medicine which is transferred after Perry Expedition is academically meaningful. This study searched publications, which were listed on Open-Access databases by Dec. 11th, 2019. We collected research articles which had been published from January 3rd, 1867 to July 30th, 1912 also known as Meiji era and uploaded on Open-Access databases. Our searching databases were J-stage, CiNii (Scholarly and Academic Information Navigator), Tokyo Metropolitan Library, The National Diet Library, IRDB (Institutional Repositories DataBase) and KAKEN (Grant-in-Aid for Scientific Research Database). Searching keywords were cannabis, hemp and all their Japanese synonyms and available combinations. We selected final 15 studies which met every selection criteria in the 346,393 collected studies. Cannabis was prescribed in Meiji era of Japan to alleviate pain and cure the digestive, respiratory, urinary, and nervous system diseases such as indigestion, asthma, tuberculosis, gonorrhea and its complications, insomnia, and nervous prostration. Cannabis was medically used in Meiji era of Japan and the reporting and sharing of its clinical effect was published on the medical journals like present days. There were already Cannabis regulations in that era, but its medicinal use was more liberated than nowadays. It may be a chance to reconsider the current legal system, which strictly controls the use of Cannabis.

Case Series Study on the Use of BU Pharmacopuncture Treatment in Patients with Acute Lumbar Sprain.

OBJECTIVE: The purpose of this study was to investigate the clinical effects of BU pharmacopuncture therapy consisting of bear's gall(fel ursi) and ox bezoar(bovis calculus) on acute lumbar sprain. METHODS: 12 patients diagnosed as acute lumbar sprain in 6 designated local Korean medicine clinics from October 2017 to February 2018 were treated by BU pharmacopuncture. Several acupoints in abdomen and lumbar region were selected by clinicians at their own discretion. The effectiveness of the therapy was evaluated using VAS and ODI. After that we reviewed the medical records of all these patients to evaluate the effectiveness and safety of the therapy. RESULTS: The VAS and ODI scales were significantly decreased after BU pharmacopuncture therapy. And no major complications and adverse effects were reported. CONCLUSION: BU pharmacopuncture showed rapid pain relief in patients with acute lumbar sprain. It is possible to shorten the treatment period of acute lumbar sprain and prevent progressing to chronic back pain in advance. To establish the effects of BU pharmacopuncture therapy, more succeeding clinical and laboratory studies are needed.

Gyejigachulbu-Tang Relieves Oxaliplatin-Induced Neuropathic Cold and Mechanical Hypersensitivity in Rats via the Suppression of Spinal Glial Activation.

Activation of spinal glial cells plays a crucial role in the pathogenesis of neuropathic pain. An administration of oxaliplatin, an important anticancer drug, often induces acute neuropathic cold hypersensitivity and/or mechanical hypersensitivity in patients. Gyejigachulbu-tang (GBT), a herbal formula comprising Cinnamomi Cortex, Paeoniae Radix, Atractylodis Lanceae Rhizoma, Zizyphi Fructus, Glycyrrhizae Radix, Zingiberis Rhizoma, and Aconiti Tuber, has been used in East Asia to treat various pain symptoms, especially in cold patients. This study investigated whether and how GBT alleviates oxaliplatin-induced cold and mechanical hypersensitivity in rats. The behavioral signs of cold and mechanical hypersensitivity were evaluated by a tail immersion test in cold water (4°C) and a von Frey hair test, respectively. The significant cold and mechanical hypersensitivity were observed 3 days after an oxaliplatin injection (6 mg/kg, i.p.). Daily oral administration of GBT (200, 400, and 600 mg/kg) for 5 days markedly attenuated cold and mechanical hypersensitivity. Immunoreactivities of glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker) in the spinal dorsal horn were significantly increased by an oxaliplatin injection, which were restored by GBT administration. These results indicate that GBT relieves oxaliplatin-induced cold and mechanical hypersensitivity in rats possibly through the suppression of spinal glial activation.