Content-based image retrieval for the diagnosis of myocardial perfusion imaging using a deep convolutional autoencoder.

BACKGROUND: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) plays a crucial role in the optimal treatment strategy for patients with coronary heart disease. We tested the feasibility of feature extraction from MPI using a deep convolutional autoencoder (CAE) model. METHODS: Eight hundred and forty-three pairs of stress and rest myocardial perfusion images were collected from consecutive patients who underwent cardiac scintigraphy in our hospital between December 2019 and February 2022. We trained a CAE model to reproduce the input paired image data, so as the encoder to output a 256-dimensional feature vector. The extracted feature vectors were further dimensionally reduced via principal component analysis (PCA) for data visualization. Content-based image retrieval (CBIR) was performed based on the cosine similarity of the feature vectors between the query and reference images. The agreement of the radiologist's finding between the query and retrieved MPI was evaluated using binary accuracy, precision, recall, and F1-score. RESULTS: A three-dimensional scatter plot with PCA revealed that feature vectors retained clinical information such as percent summed difference score, presence of ischemia, and the location of scar reported by radiologists. When CBIR was used as a similarity-based diagnostic tool, the binary accuracy was 81.0%. CONCLUSION: The results indicated the utility of unsupervised feature learning for CBIR in MPI.

Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens.

During the course of our studies towards the identification of promising chemotherapeutic candidates from plants against two human T-cell lymphotropic virus type I-infected T-cell lines (MT-1 and MT-2), we screened 17 extracts from 9 rutaceous plants against MT-1 and MT-2 cells. The extracts from the aerial parts and roots of Boenninghausenia japonica, as well as the leaves and roots of Ruta graveolens showed potent antiproliferative effects. After activity-guided fractionation, we isolated 44 compounds from two rutaceous plants, including three new compounds (1-3), which were classified into 26 coumarin analogs (13 coumarins, 8 furanocoumarins, 4 dihydrofuranocoumarins and one dihydropyranocoumarin), 15 alkaloid analogs (7 quinolone alkaloids, 4 acridone alkaloids, 3 furanoquinoline alkaloids and one tetrahydroacridone alkaloid) and 3 flavonoid glycosides. Structure-activity relationship studies were also evaluated. The coumarin compounds (2, 3 and 7-9) bearing a 3-dimethylallyl moiety showed potent activity. Similarly, of all the furanocoumarins evaluated in the current study, compound 17 bearing a 3-dimethylallyl group also showed potent activity. A dihydrofuranocoumarin (27) bearing a 3-dimethylallyl moiety showed the most potent activity. Following 27, compound 28 showed potent activity. These results therefore suggested that the presence of a 3-dimethylallyl moiety was important to the antiproliferative activity of these coumarin analogs.

Screening of promising chemotherapeutic candidates from plants extracts.

Over the course of our studies investigating anti-proliferative properties of compounds originating from plants against human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), murine melanoma (B16F10), and two human T cell lymphotropic virus type 1 (HTLV-1)-infected T-cell lines (MT-1 and MT-2), we have screened 582 extracted samples obtained from a variety of parts from 370 plants. A few extracts showed anti-proliferative activity against all cell lines, but upon further investigation, toxicity toward selected cell lines was recognized. After activity-guided fractionation, isolation of the active principles was achieved. Structure-activity relationship studies identified the components and functionalities responsible for the specific selectivity against each cancer cell line. The effect of polyacetylenes against MK-1 cells was more potent than against HeLa and B16F10 cells. The compound having a 3,4-dihydroxyphenethyl group also showed an anti-proliferative effect against B16F10 cells. Some 6-methoxyflavone derivatives and 8-hydroxy furanocoumarins were good inhibitors of HeLa cell growth. The 17 compounds whose EC50 values were less than 1 nM did not show specific cellular selectivity. Because the cytotoxic effect of 24, 25-dihydrowithanolide D toward control cells was observed at a concentration about 100 times higher than those for the cancer cell lines, withanolide was identified as the most promising chemotherapeutic candidate in our experiments.

Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (IV): phenanthroindolizidine alkaloids from Tylophora tanakae leaves.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature peripheral T lymphocytes caused by human T-cell lymphotropic virus type 1 (HTLV-1). There are an estimated 5 million to 20 million HTLV-1-infected individuals worldwide; their lifetime risk of developing ATL is 3-5 %, and high HTLV-1 proviral loads have been shown to be an independent risk factor. Although conventional chemotherapeutic regimens used against other malignant lymphomas have been administered to ATL patients, the prognosis is often poor. In previous studies, we screened 459 extracts from 344 plants to isolate components exhibiting antiproliferative activity against HTLV-1-infected T-cell lines (MT-1 and MT-2). In our continuing search for potential anti-HTLV-1 natural products, 15 extracts of Asclepiadaceae plants were further tested against MT-1 and MT-2 cells. The MeOH extract of aerial parts of Tylophora tanakae showed antiproliferative activity. Activity-guided fractionation resulted in the isolation of 6 phenanthroindolizidine alkaloids (including a new compound), and we examined their antiproliferative activity against MT-1 and MT-2 cells. The EC50 value of some of the alkaloids was in the low nanomolar range, comparable to that of the clinically used antineoplastic drug doxorubicin. Structure-activity relationship analyses suggested that a 14ß-hydroxy moiety is essential for activity against HTLV-1-infected T cells. In contrast, the presence of a 2-methoxy moiety, a 7-methoxy moiety, or an N-oxide moiety appears to reduce the potency of the antiproliferative activity against HTLV-1-infected T cells.

Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (III).

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature peripheral T lymphocytes caused by human T-cell lymphotropic virus type I (HTLV-I). In our previous paper, 214 extracts from 162 plants were screened to elucidate the anti-proliferative principles against HTLV-I-infected T-cell lines. In this study, 245 extracts from 182 plants belonging to 61 families were further tested against two HTLV-I-infected T-cell lines (MT-1 and MT-2). Potent anti-proliferative effects were exhibited against MT-1 and MT-2 cells by 52 and 60 of the 245 extracts tested, respectively. Of these, two extracts showed strong inhibitory activity (EC50 values 0.1-1 µg/mL; +++) against both cells, 7 extracts showed moderate inhibitory activity (EC550 values 1-10 µg/mL; ++), and 43 extracts showed weak inhibitory activity (EC50 values 10-100 µg/mL; +), whereas the remaining extracts did not show any activity (EC50 values >100 µg/mL; -) against MT-1 cells. On the other hand, 10 extracts showed moderate inhibitory activit and, 48 extracts showed weak inhibitory activity, whereas the remaining extracts did not show any activity against MT-2 cells. Extracts from the aerial parts of Annona reticulata and A. squamosa showed the most potent inhibitory activity and three aporphine alkaloids were isolated from their extracts as the active principles by activity-guided fractionation.

Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles from Physalis pruinosa and structure-activity relationships with withanolides.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I (HTLV-1). Clinical manifestations of ATL range from smoldering to chronic, lymphoma and acute subtypes. Patients with acute and lymphoma-type ATL require therapeutic intervention. Conventional chemotherapeutic regimens used against other malignant lymphoma have been administered to ATL patients, but the therapeutic outcomes of acute and lymphoma-type ATL remain very poor. In this study, 214 extracts from 162 plants belonging to 65 families were screened for the purpose of elucidating the anti-proliferative effect against HTLV-1-infected T-cell lines. Extracts from aerial parts of Physalis pruinosa showed potent inhibitory effect. We isolated five withanolides from the extracts by activity-guided fractionation and examined the structure-activity relationships. The presence of a 5ß,6ß-epoxy function is suggested to be essential for the activity, and the most active principle showed selective toxicity to HTLV-1-infected T-cell lines.

Resistance in the plant, Barbarea vulgaris, and counter-adaptations in flea beetles mediated by saponins.

Three saponins and two sapogenins had differential effects on food consumption in five near-isogenic flea beetle lines, which differ in their ability to utilize a novel host plant, Barbarea vulgaris (Brassicaceae). The ability to live on this plant is controlled by major, dominant R-genes in the flea beetle, Phyllotreta nemorum (Coleoptera: Chrysomelidae: Alticinae). A susceptible genotype (rr) is unable to live on the plant, whereas resistant genotypes (RR and Rr) can utilize the novel host plant. Among compounds isolated from B. vulgaris, hederagenin cellobioside (hederagenin-3-O-(4-O-beta-D-glucopyranosyl)-beta-D-glucopyranoside) inhibited feeding, whereas the effect of oleanolic acid cellobioside was much weaker. The aglycones (sapogenins) were inactive. Although hederagenin cellobioside was active against all flea beetle lines, its effect on food consumption was much stronger on the susceptible genotype (rr) compared to the resistant genotype (Rr). Susceptible and resistant flea beetle genotypes were equally sensitive to a non-host saponin, alpha-hederin (hederagenin-3-O-(2-O-alpha-L-rhamnopyranosyl)-alpha-L-arabinopyranoside). These results suggest that R-alleles in flea beetles might be specific adaptations to defensive saponins in B. vulgaris. A possible mechanism of action of the R-alleles might be to encode for an enzyme (e.g. a glucosidase), which is able to cleave glycosidic bonds in hederagenin cellobioside, but not in alpha-hederin. The potential role of saponins as defensive compounds in B. vulgaris and as targets for counter-adaptations in flea beetles and other insects is discussed.

Antiproliferative constituents from umbelliferae plants. IX. New triterpenoid glycosides from the fruits of Bupleurum rotundifolium.

The MeOH extract of the fruits of Bupleurum rotundifolium showed inhibitory activity against human gastric adenocarcinoma (MK-1) cell growth. Bioactivity-guided fractionation of the MeOH extract led to the isolation of four new triglycosides of 13beta,28-epoxy oleanane-type triterpenes, named rotundiosides O, Q, S and T; 12 new glycosides of oleanane-type triterpenes, named rotundiosides J-N, P, R, U-Y, and others; echinocystic acid 3-O-sulfate; and three known oleanane-type triterpene glycosides, rotundiosides A, F and G. The structures of the new isolates were determined based on chemical and spectroscopic evidence. The GI(50) of isolates against MK-1, HeLa and B16F10 cell lines are reported.

Immunomodulatory effect and quantitation of a cytotoxic glycosphingolipid from Murdannia loriformis.

NMR signal reassignments for a cytotoxic glycosphingolipid compound, 2, ß-O-D-glucopyranosyl-2-(2'-hydroxy-Z-6'-enecosamide)sphingosine, isolated from an ethanolic extract of the herb Murdannia loriformis, have been achieved by use of FAB-MS, and 1D and 2D 1H and 13C NMR. The amount of 2 in the herb juice was quantitatively determined by use of a validated HPLC method (RP-18, MeOH-H2O, UV detection at 210 nm). The immunomodulatory effect of the herb juice and of 2 was proved by means of in vitro cellular immunological assays. Compound 2 at a concentration of 13 nmol L-1 stimulated PBMC proliferation and increased the CD 3,4:CD 3,8 ratio in T lymphocytes.

Antibacterial activity of crude extracts from Mexican medicinal plants and purified coumarins and xanthones.

Thirty-two extracts from 22 Mexican medicinal plants of 15 different families were assayed to determine their antibacterial activity against Escherichia coli and Staphylococcus aureus. Seventeen plants showed antibacterial activity, while five plants showed no activity against both bacteria. All of the extracts showed higher activity against Staphylococcus aureus (methicillin-sensitive and methicillin-resistant) than against Escherichia coli, except one. Among the plants examined, Bursera simaruba (L.) Sarg. (Burseraceae), Haematoxylum brasiletto H. Karst. (Fabaceae), Calophyllum brasiliense Cambess. (Clusiaceae), and Mammea americana L. (Clusiaceae) were highly active against Staphylococcus aureus. Coumarins (mammea A/BA and mammea A/AA) and xanthones, namely jacareubin and 1,3,5,6-tetrahydroxy-2-(3,3-dimethylallyl) xanthone, were isolated as the principle compounds from the last two plants.

Antiproliferative constituents from Umbelliferae plants VII. Active triterpenes and rosmarinic acid from Centella asiatica.

The antiproliferative constituents in the MeOH extract from the aerial parts of Centella asiatica were investigated. Activity-guided fractionation of MeOH extract resulted in the isolation of ursolic acid lactone, ursolic acid, pomolic acid, 2alpha,3alpha-dihydroxyurs-12-en-28-oic acid, 3-epimaslinic acid, asiatic acid, corosolic acid, and rosmarinic acid. Antiproliferative activity of the isolated compounds against human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), and murine melanoma (B16F10) cells was estimated.

Antiproliferative constituents in plants 14. Coumarins and acridone alkaloids from Boenninghausenia japonica NAKAI.

The MeOH extracts of the ground part and the root of Boenninghausenia japonica NAKAI showed inhibitory activity against tumor cell growth. Fractionation of the extracts has resulted in isolation of 1,3-dihydroxy-4-(2'-hydroxy-3'-hydroxymethyl-3',4'-epoxy-butyl)-N-methylacridone, 1,3-dihydroxy-4-[(Z)-3'-hydroxy-3'-methyl-buten-1'-yl]-N-methylacridone, 3-(1',1'-dimethylallyl)-7-hydroxy-8-methoxy-2H-1-benzopyran-2-one, casegravol, cis-casegravol, and edgeworin in addition to 9 compounds reported from B. japonica and B. albiflora. The isolates from this plant and some related compounds were tested for antiproliferative activity against human gastric adenocarcinoma (MK-1), human uterus carcinoma (HeLa), and murine melanoma (B16F10) cells.

Interactions of phytoestrogens with estrogen receptors alpha and beta (III). Estrogenic activities of soy isoflavone aglycones and their metabolites isolated from human urine.

Two glucuronides (4'-O-, and 7-O-) and a glucuronyl (7-O-) sulfate (4'-O-) of genistein, two glucuronides (4'-O-, and 7-O-) and a glucuronyl (7-O-) sulfate (4'-O-) of daidzein, 7-O-glucuronides of glycitein, dihydrodaidzein and O-desmethylangolensin were isolated from the urine of volunteer subjects fed soy bean curds (Tofu). The estrogenic activities, i.e., i) the effect on the estrogen-dependent growth of MCF-7 cells, ii) the binding ability to human estrogen receptors (hERs) alpha and beta, and iii) the effect on hER-dependent beta-galactosidase induction, of these isoflavone metabolites were examined. Two synthetic isoflavone aglycones (dihydrodaidzein and O-desmethylangolensin) and four synthetic sulfates (4'-O- and 4'-, 7-di-O-) of genistein and daidzein were also studied for their estrogenic activities for the purpose of comparison. With respect to estrogenic acivity, the tested isoflavone metabolites were classified into three groups. The first group shows a very poor stimulatory effect toward the growth of MCF-7 cells, binding activity, and beta-galactosidase induction. The sulfates belong to this group. The second group shows a moderate binding activity but poor stimulation and beta-galactosidase induction. Some glucuronyl conjugates belong to this group. The last group shows a moderate stimulation and beta-galactosidase induction but poor binding activity. A mixed type of conjugates having glucuronyl and sulfony moieties belong to this group.

Trypanocidal constituents in plants 4. Withanolides from the aerial parts of Physalis angulata.

The constituents of the aerial parts of Physalis angulata (Solanaceae) were investigated based on the plant's trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent for Chagas' disease. Four new withanolides were isolated, along with six known ones, from the active fraction. Their structures were determined by spectroscopic analysis. Trypanocidal activity against trypomastigotes, an infectious form of T. cruzi, was also estimated, as well as cytotoxic activity against human uterine carcinoma (HeLa) cells in vitro. Evaluation of trypanocidal activity using the colorimetric reagent Cell Counting Kit-8 was also examined.

Antiproliferative activity of the main constituents from Phyllanthus emblica.

Eighteen main compounds, including four norsesquiterpenoids (1-4) and 14 phenolic compounds (5-18) isolated previously from Phyllanthus emblica, together with a main constituent, proanthocyanidin polymers (19) identified at this time from the roots, were estimated for their antiproliferative activities against MK-1 (human gastric adenocarcinoma), HeLa (human uterine carcinoma), and B16F10 (murine melanoma) cells using an MTT method. All of the phenolic compounds including the major components 5-8 from the fruit juice, 8, 9, and 12 from the branches and leaves, and 19 from the roots showed stronger inhibition against B16F10 cell growth than against HeLa and MK-1 cell growth. Norsesquiterpenoid glycosides 3 and 4 from the roots exhibited significant antiproliferative activities, although their aglycon 1 and monoglucoside 2 showed no inhibitory activity against these tumor cells.

Trypanocidal constituents in plants 3. Leaves of Garcinia intermedia and heartwood of Calophyllum brasiliense.

The constituents of the leaves of Garcinia intermedia and heartwood of Calophyllum brasiliense were investigated based on their trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent of Chagas' disease. As the active components, the polyisoprenylated benzophenone derivative guttiferone A and the xanthone 8-desoxygartanin were isolated along with the biflavonoids podocarpusflavone A and amentoflavone, and friedelin from the former. Three xanthones, jacareubin, 6-deoxyjacareubin, and 1,3,5,6-tetrahydroxy-2-(3-methyl-2-butenyl)xanthone from the latter showed activity. The trypanocidal activity of these compounds against trypomastigotes, an infectious form of T. cruzi, was examined as well as gossypol, berberine chloride, and harmine for comparison.

Trypanocidal constituents in plants 2.xanthones from the stem bark of Garcinia subelliptica.

The constituents of the stem bark of Garcinia subelliptica (Guttiferae) were investigated based on its trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent for Chagas' disease. As the active components, nine xanthones were isolated including two new ones, 4-hydroxybrasilixanthone B and 1,3,5,6-tetrahydroxy-4,7,8-tri(3-methyl-2-butenyl)xanthone. Their structures were determined by spectroscopic analysis. Trypanocidal activity against trypomastigotes, an infectious form of T. cruzi, was also estimated as well as cytotoxic activity. Fukugetin, the major component of the bark, showed no activity.

Hepatoprotective constituents in plants. 14. Effects of soyasapogenol B, sophoradiol, and their glucuronides on the cytotoxicity of tert-butyl hydroperoxide to HepG2 cells.

The effects of soyasapogenol B, sophoradiol, their glucuronides, and glycyrrhizin on the hepatotoxicity of tert-butyl hydroperoxide (t-BuOOH) in a human-liver-derived cell line (HepG2 cells) were investigated. Glycyrrhizin showed significant dose-dependent protective effects against the cytotoxicity of t-BuOOH. Among soyasapogenol B and its glucuronides, the monoglucuronide showed the most potent hepatoprotective activity, followed by soyasapogenol B itself. Soyasaponin III was weakly protective, while soyasaponin I increased the toxicity of t-BuOOH. Among sophoradiol and its glucuronides, sophoradiol itself showed the most potent hepatoprotective activity, which was equal to glycyrrhizin, while the monoglucuronide and kaikasaponin III showed an increase in cytotoxicity. These results were considerably different from those reported previously on the protective effects of these compounds using primary cultures of immunologically injured rat liver cells. Consequently, the hepatoprotective action of the triterpene derivatives investigated would be different in HepG2 cells and in rat primary hepatocyte cultures.