A Novel Computational Approach for the Discovery of Drug Delivery System Candidates for COVID-19.

In order to treat Coronavirus Disease 2019 (COVID-19), we predicted and implemented a drug delivery system (DDS) that can provide stable drug delivery through a computational approach including a clustering algorithm and the Schrödinger software. Six carrier candidates were derived by the proposed method that could find molecules meeting the predefined conditions using the molecular structure and its functional group positional information. Then, just one compound named glycyrrhizin was selected as a candidate for drug delivery through the Schrödinger software. Using glycyrrhizin, nafamostat mesilate (NM), which is known for its efficacy, was converted into micelle nanoparticles (NPs) to improve drug stability and to effectively treat COVID-19. The spherical particle morphology was confirmed by transmission electron microscopy (TEM), and the particle size and stability of 300-400 nm were evaluated by measuring DLSand the zeta potential. The loading of NM was confirmed to be more than 90% efficient using the UV spectrum.

Phellopterin isolated from Angelica dahurica reduces blood glucose level in diabetic mice.

Insulin resistance is the critical condition for the development of metabolic syndromes including type II diabetes and heart disease. To investigate the active components of Angelica dahurica root which is known to increase insulin sensitivity, its methanol extract was subfractionated. The ethyl acetate (EtOAc) fraction of the Angelica dahurica root extract significantly promoted adipocyte differentiation in 3T3-L1 preadipocyte cells. Among the three compounds isolated from the EtOAc extract (bergapten (1), imperatorin (2) and phellopterin (3)), phellopterin (3) induced the highest adipocyte differentiation at 25 and 50 µg/mL. In addition, treatment with imperatorin (2) and phellopterin (3) increased the mRNA expression of peroxisome proliferator-activated receptors γ (PPARγ). In diabetic animal model induced by high-fat diets (HFD) and streptozotocin (STZ), administration of phellopterin ((3), 1 mg/kg and 2 mg/kg) significantly reduced the levels of blood glucose, triglycerides and total cholesterol. Taken together, these results indicate that phellopterin (3) enhances adipocytes differentiation in 3T3-L1 preadipocytes, phellopterin (3) significantly prevents HFD/STZ-induced type Ⅱ diabetes. The present study also provides phellopterin (3) may be a valuable therapeutic alternative for enhancing insulin sensitivity through promotion of adipocyte differentiation and by increasing mRNA expression levels of PPARγ, which is a major mediator of insulin sensitivity.

Unilateral femoral fracture in a low birth weight infant: a case report.

Femoral fractures due to birth trauma are an extremely rare but important birth injury. While vaginal breech delivery, although rare, can cause femur fracture, abdominal breech delivery is not expected to cause fracture. Here we report on a low birth weight infant who was delivered by cesarean section for breech presentation at 30 1/7 weeks of gestation and sustained a unilateral fracture of the femoral shaft.

Peritoneal carcinomatosis mimicking a peritoneal tuberculosis.

Symptoms of a peritoneal progression from ovarian cancer are nonspecific such as abdominal pain, abdominal distention and more. Many imaging studies and serum CA-125 help diagnosis. However, it is difficult to exclude the instances of the diffuse peritoneal diseases that mimic carcinomatosis. The elevated CA-125 level usually correlates with the peritoneal carcimatosis, but it is often found in other peritoneal diseases. Therefore, the pathologic confirmation is necessary because of other mimicking diseases. In our case, CA-125 levels were elevated. Abdominal computed tomography finding was suspected a peritoneal tuberculosis but the pathologic result was the peritoneal carcimatosis, eventually.

Recto-Bartholin's duct fistula: a case report.

Bartholin's duct cysts, the most common growths in the vulva, occur in the labia majora. The cyst may become infected, and an abscess may develop in the gland. Rectovaginal fistula is a rare complication and its formation is secondary to Bartholin's cyst; only 4 cases have been reported in the literature so far. In this case, the fistula was located between the rectum and a Bartholin's duct, rather than the vagina and the rectum. We present the first case of a recto-Bartholin's duct fistula, performed surgical excision and fistulectomy. Postoperative treatment with antibiotics resulted in the complete resolution of all lesions at the 3-month follow-up.

The analgesic and anti-inflammatory effects of Litsea japonica fruit are mediated via suppression of NF-κB and JNK/p38 MAPK activation.

Fruits of the Litsea family of trees and shrubs contain biologically active compounds, some of which have been used as natural nutrients and flavoring agents in food. In this study, we identified novel anti-nociceptive effects of the 30% ethanol extract, the CH(2)Cl(2) fraction and the associated active components (Hamabiwalactone A and B) from Litsea japonica fruit by using in vivo peripheral and central nervous pain models. In addition, we compared the anti-inflammatory effects of several fractions from L. japonica fruit extracts using lipopolysaccharide (LPS)-stimulated Raw264.7 cells. The CH(2)Cl(2) fraction of L. japonica fruit (LJM) had an optimal combination of anti-inflammatory effects and low cytotoxicity. Dose response studies were performed to determine the inhibitory effects of LJM on the pro-inflammatory enzymes, COX-2/PGE(2) and NO/iNOS, and pro-inflammatory cytokines, IL-1ß, IL-6, and TNF-α. Molecular profiling revealed that LJM exerts anti-inflammatory effects through inhibition of NF-κB and JNK/p38 MAPK signaling in LPS-induced macrophages. This study suggests that CH2Cl2 fraction of L. japonica fruit and its bioactive components are potential candidates as anti-inflammatory and analgesic agents (painkillers) for the treatment of inflammatory diseases.

Immunomodulatory effects of Liriope platyphylla water extract on lipopolysaccharide-activated mouse macrophage.

The tuber of Liriope platyphylla Wang et Tang (Liliaceae), also known as Liriopis tuber, is famous in Oriental medicine owing to its tonic, antitussive, expectorant and anti-asthmatic properties. In the present study, the effects of Liriopis tuber water extract (LP) on proinflammatory mediators secreted from lipopolysaccharide (LPS)-induced cultured RAW 264.7 mouse macrophages were investigated. Nitric oxide (NO), prostaglandin E2 (PGE2) and intracellular calcium release were measured after 24 h incubation. Various cytokines and nuclear transcription factors (NF-κB and CREB) of LPS-induced RAW 264.7 were measured by a multiplex bead array assay based on xMAP technology. LP (up to 200 μg/mL) significantly decreased levels of nitric oxide (NO), interleukin (IL)-6, IL-10, IL-12p40, interferon-inducible protein-10, keratinocyte-derived chemokine, monocyte chemotactic protein-1, vascular endothelial growth factor, granulocyte macrophage-colony stimulating factor, platelet derived growth factor, PGE2, intracellular calcium, NF-κB and CREB in LPS-induced RAW 264.7 cells (p < 0.05). The results suggest that LP has immunomodulatory activity to reduce excessive immune reactions during the activation of macrophages by LPS. Further studies are needed to verify the precise mechanism regulating immunomodulatory activities of LP.