Proposal for structure revision of pinofuranoxin A through total syntheses of stereoisomers.

The relative configuration of the epoxide functionality in pinofuranoxin A (1), α-alkylidene-ß-hydroxy-γ-methyl-γ-butyrolactone with trans-epoxy side chain isolated by Evidente et al. in 2021, was revised by DFT-based spectral reinvestigations and stereo-controlled synthesis. The present investigation demonstrates the difficulty of the configurational elucidation of the stereogenic centers on the conformationally flexible acyclic side-chains. Sharpless's enantioselective epoxidations and dihydroxylations were quite effective in the reinvestigations of the configurations. As our syntheses made all diastereomers available, these would be quite effective in the next structure-biological activity relationship studies.

Therapeutic effect of ouabagenin, a novel liver X receptor agonist, on atherosclerosis in nonalcoholic steatohepatitis in SHRSP5/Dmcr rat model.

The liver X receptor (LXR) can enhance cholesterol transporters, which could remove excess cholesterol from foam cells in atheromas. LXR has two subtypes: LXRα, which aggravates hepatic lipid accumulation, and LXRß, which does not. In 2018, ouabagenin (OBG) was reported as a potential LXRß-specific agonist. We aimed to examine whether OBG specifically affects LXRß in nonalcoholic steatohepatitis (NASH); it did not aggravate hepatic steatosis and can suppress the development of atherosclerosis. SHRSP5/Dmcr rats fed a high-fat and high-cholesterol diet were divided into four groups as follows: (I) L-NAME group, (II) L-NAME/OBG group, (III) OBG (-) group, and (IV) OBG (+) group. All groups' rats were intraperitoneally administered L-NAME. The L-NAME/OBG group's rats were intraperitoneally administered OBG and L-NAME simultaneously. After L-NAME administration, the OBG (+) group's rats were administered OBG, while the OBG (-) group's rats were not. Although all rats developed NASH, OBG did not exacerbate steatosis (L-NAME/OBG and OBG (+) groups). In addition, endothelial cells were protected in the L-NAME/OBG group and foam cells in the atheroma were reduced in the OBG (+) group. OBG is an LXRß-specific agonist and has a potential therapeutic effect on atherosclerosis without developing lipid accumulation in the liver.

Snapping Knee Syndrome of the Sartorius Accompanying Osteoarthritis Cured by Osteophyte Removal During Total Knee Arthroplasty.

Snapping knee syndrome on the medial side is rare. Here, we report the case of a patient with snapping knee syndrome of the sartorius with knee osteoarthritis. A large osteophyte at the posteromedial femoral condyle impinged on the sartorius myotendinous junction, causing painless snapping. The patient was successfully treated with osteophyte removal and total knee arthroplasty while preserving the tendon. Hence, tendon release or resection to treat snapping syndrome is not always necessary if the underlying cause can be eliminated. Furthermore, we found that while tendon tension is important for the occurrence of snapping syndrome, the impingement site determines the occurrence of snapping pain.

In vivo metal-catalyzed SeCT therapy by a proapoptotic peptide.

Selective cell tagging (SeCT) therapy is a strategy for labeling a targeted cell with certain chemical moieties via a catalytic chemical transformation in order to elicit a therapeutic effect. Herein, we report a cancer therapy based on targeted cell surface tagging with proapoptotic peptides (Ac-GGKLFG-X; X = reactive group) that induce apoptosis when attached to the cell surface. Using either Au-catalyzed amidation or Ru-catalyzed alkylation, these proapoptotic peptides showed excellent therapeutic effects both in vitro and in vivo. In particular, co-treatment with proapoptotic peptide and the carrier-Ru complex significantly and synergistically inhibited tumor growth and prolonged survival rate of tumor-bearing mice after only a single injection. This is the first report of Ru catalyst application in vivo, and this approach could be used in SeCT for cancer therapy.

Structure-Activity Relationship of Anti-malarial Allylpyrocatechol Isolated from Piper betle.

Malaria disease remains a serious worldwide health problem. In South-East Asia, one of the malaria infection "hot-spots," medicinal plants such as Piper betle have traditionally been used for the treatment of malaria, and allylpyrocatechol (1), a constituent of P. betle, has been shown to exhibit anti-malarial activities. In this study, we verified that 1 showed in vivo anti-malarial activity through not only intraperitoneal (i.p.) but also peroral (p.o.) administration. Additionally, some analogs of 1 were synthesized and the structure-activity relationship was analyzed to disclose the crucial sub-structures for the potent activity.

Toosendanin relatives, trypanocidal principles from Meliae Cortex.

Africa Trypanosomiasis remains a serious health problem, but the approved drugs for this disease are so few that novel trypanocidal compounds are demanded. In search for trypanocidal principles from medicinal plants, we found MeOH extracts of Meliae Cortex with potent activity through the screening from about 300 kinds of methanolic extract. By bioassay-guided fractionation from this extract through the liquid-liquid partition and subsequent chromatographic technique using silica gel and ODS, finally we disclosed toosendanin (1) and its relatives as active principles. These active congeners showed not only potent trypanocidal activity but also little cytotoxicity to display the excellent selective index. Taking the isolated amount as well as trypanocidal activity into consideration, 1 was disclosed to be the responsible active principle in Meliae Cortex. Additionally, the derivatives of 1 were chemically prepared from 1 and bioactivity of them were also evaluated. Through the comparison with their trypanocidal activity among the isolated relatives and the synthesized derivatives of 1, the epoxide moiety was revealed to be essential for their potent trypanocidal activity. Furthermore, 3-O-acetyl group and 7-hydroxyl group were presumed to be important functional groups and introduction of methylpropionyl group into hemiacetal hydroxy moiety was clarified to enhance their typanocidal activity.

Oenothein B, dimeric hydrolysable tannin inhibiting HCV invasion from Oenothera erythrosepala.

The envelope proteins of the hepatitis C virus (HCV), E1 and E2, have been revealed to be essential for invasion of HCV. Thus, we were engaged in the search for the inhibitors against HCV invasion through the assay system using the model virus expressing recombinant HCV envelopes, E1 and E2. Now, we disclosed dimeric hydrolysable tannin oenothein B (1) from MeOH extract of Oenothera erythrosepala as an active principle for inhibition of HCV invasion and its potency was almost the same as that of monomeric hydrolysable tannin, tellimagrandin I (2). Furthermore, by use of stereoselectively prepared 1-ß- and 1-α-O-methyl tellimagrandin Is (4 and 5), the introduction of methyl moiety into 1-hydroxy group of 2 was clarified to result in slightly reduction of activity and ß-isomer was revealed to exhibit a little stronger activity than α-one.

Synthesis of 5-Aryl-3(2 H)-furanones Using Intramolecular Cyclization of Sulfonium Salts.

Base-induced intramolecular cyclization of novel (4-aryl-2,4-dioxobutyl)methylphenylsulfonium salts prepared from the commercially available 1-arylethanone by a cost-effective process is described in this paper. The reaction was completed within 10 min to produce a family of 2-unsubstituted 5-aryl-3(2 H)-furanones in excellent yield. This procedure is simple, and can be carried out under mild conditions and an ambient atmosphere.

Inhibitor for FcεRI expression on mast cell from Verbasucum thapsus L.

We found out 2',3'-dihydroxypuberulin from South American medicinal plant, V. thapsus L., as a candidate of an anti-allergic lead which inhibits the expression of high-affinity receptor of IgE (FcεRI) on the surface of mast cells. Furthermore, the analysis of structure-activity relationship by using synthesized 2',3'-dihydroxypuberulin analogs revealed that both hydroxy groups in the side chain and both of methyl moieties on phenolic hydroxy groups were crucial for potent activity, but absolute configuration of C-3' position wasn't. The active principle, 2',3'-dihydroxypuberulin, was disclosed to down-regulate the mRNA level of ß-chain of FcεRI, different from previous reported active natural product reducing γ-chain level.

Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect.

Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking studies suggested that OBG has LXR-selective agonistic activity. In addition, OBG repressed the expression of epithelial sodium channel (ENaC), a LXR target gene, without causing hepatic steatosis, a typical side effect of conventional LXR ligands. This remarkable biological activity can be attributed to a unique mode of action; the LXR agonist activity mainly proceeds through the LXRß subtype without affecting LXRα, unlike conventional LXR ligands. Thus, OBG is a novel class of LXR ligand that does not cause severe side effects, with potential for use as an antihypertensive diuretic or a tool compound for exploring LXR subtype-specific biological functions.

N-Alkylation Using Sodium Triacetoxyborohydride with Carboxylic Acids as Alkyl Sources.

A versatile N-alkylation was performed using sodium triacetoxyborohydride and carboxylic acid as an alkyl source. The combination of these reagents furnished products different from those given previously by a similar reaction. Moreover, the mild conditions of our method allowed some functional groups to remain through the reaction, whereas they would react and be converted into other moieties in the similar reductive N-alkylation reported previously. Herein, we provide a new procedure for the preparation of various compounds containing nitrogen atoms.

Helically Chiral 1-Sulfur-Functionalized [6]Helicene: Synthesis, Optical Resolution, and Functionalization.

The synthesis and optical resolution of helically chiral 5,6,9,10-tetrahydro-1-[6]helicenethiol and its subsequent transformations to enantiopure 1-sulfur-functionalized [6]helicenes are reported. A novel enantiopure [7]thiahelicene having a thiophene ring at the terminal position of the [6]helicene skeleton was synthesized.

Synthesis of 4-Halo-3(2H)-furanones Using Intramolecular Cyclization of Sulfonium Salts.

A simple and efficient synthesis of 4-halo-3(2H)-furanones by halogenative intramolecular cyclization of sulfonium salts is described, which can expedite the production of a variety of 4-bromo- or 4-iodo-3(2H)-furanones, useful synthetic building blocks, in good to high yield under mild conditions.

The plant cell-wall enzyme AtXTH3 catalyses covalent cross-linking between cellulose and cello-oligosaccharide.

Cellulose is an economically important material, but routes of its industrial processing have not been fully explored. The plant cell wall - the major source of cellulose - harbours enzymes of the xyloglucan endotransglucosylase/hydrolase (XTH) family. This class of enzymes is unique in that it is capable of elongating polysaccharide chains without the requirement for activated nucleotide sugars (e.g., UDP-glucose) and in seamlessly splitting and reconnecting chains of xyloglucan, a naturally occurring soluble analogue of cellulose. Here, we show that a recombinant version of AtXTH3, a thus far uncharacterized member of the Arabidopsis XTH family, catalysed the transglycosylation between cellulose and cello-oligosaccharide, between cellulose and xyloglucan-oligosaccharide, and between xyloglucan and xyloglucan-oligosaccharide, with the highest reaction rate observed for the latter reaction. In addition, this enzyme formed cellulose-like insoluble material from a soluble cello-oligosaccharide in the absence of additional substrates. This newly found activity (designated "cellulose endotransglucosylase," or CET) can potentially be involved in the formation of covalent linkages between cellulose microfibrils in the plant cell wall. It can also comprise a new route of industrial cellulose functionalization.

Does Pelvic Sagittal Inclination in the Supine and Standing Positions Change Over 10 Years of Follow-Up After Total Hip Arthroplasty?

BACKGROUND: Functional anteversion and inclination of the cup change as the pelvic sagittal inclination (PSI) changes. The purposes of this study were to investigate the chronological changes of PSI during a 10-year follow-up period after total hip arthroplasty (THA) and to report the characteristics of patients who showed a greater than 10° change in the PSI from the supine to the standing position. METHODS: The subjects were 70 patients who were followed up for 10 years after THA. PSI values in the supine and standing positions were measured by 2D-3D matching using computed tomography images and pelvic radiographs. PSI values before THA and 1, 5, and 10 years after THA were compared in both the supine and standing positions. RESULTS: Supine PSI showed less than 5° of change, whereas standing PSI showed a significant decrease with time over the 10-year period. Although 43% of patients with less than 10° of difference in the PSI between the supine and standing positions before THA increased PSI posteriorly (reclining) more than 10° in standing from the supine position at 10 years, no late dislocation was observed. CONCLUSION: Supine PSI showed no significant change, but standing PSI showed a significant increase posteriorly with time over a 10-year period. However, this PSI change did not reach the level that it caused negative consequences such as late dislocation. The pelvic position in the supine position might still be a good functional reference position of the pelvis for aiming to achieve proper cup alignment at 10 years.

[Duodenal gastrointestinal stromal tumor (GIST) with deletion in exon 11 of c-kit treated with emergency pancreaticoduodenectomy due to massive bleeding: a case report].

A Japanese woman in her 50s presented with coffee-ground vomiting at a local clinic and was referred to our hospital for further investigation. Esophagogastroduodenoscopy demonstrated a submucosal tumor in the descending part of the duodenum, and she was diagnosed with a gastrointestinal stromal tumor (GIST) by other imaging studies. Elective surgery of the tumor was initially planned. However, on the 13th day of hospitalization, emergency pancreaticoduodenectomy was performed because of massive hematemesis with hemorrhagic shock. Genetic analysis demonstrated a deletion in exon 11 of the c-kit gene, which could dramatically alter the clinical course. Although duodenal GIST with active bleeding is comparatively rare, we have to assume that it is the cause of gastrointestinal bleeding and treat such cases with a minimally invasive surgical procedure and neoadjuvant/adjuvant chemotherapy. It is necessary to accumulate more cases with duodenal GIST to establish an evidence-based therapeutic strategy.

Acetabular cartilage segmentation in CT arthrography based on a bone-normalized probabilistic atlas.

PURPOSE: Determination of acetabular cartilage loss in the hip joint is a clinically significant metric that requires image segmentation. A new semiautomatic method to segment acetabular cartilage in computed tomography (CT) arthrography scans was developed and tested. METHODS: A semiautomatic segmentation method was developed based on the combination of anatomical and statistical information. Anatomical information is identified using the pelvic bone position and the contact area between cartilage and bone. Statistical information is acquired from CT intensity modeling of acetabular cartilage and adjacent tissue structures. This method was applied to the identification of acetabular cartilages in 37 intra-articular CT arthrography scans. RESULTS: The semiautomatic anatomical-statistical method performed better than other segmentation methods. The semiautomatic method was effective in noisy scans and was able to detect damaged cartilage. CONCLUSIONS: The new semiautomatic method segments acetabular cartilage by fully utilizing the statistical and anatomical information in CT arthrography datasets. This method for hip joint cartilage segmentation has potential for use in many clinical applications.