I-125 seeds brachytherapy with transcatheter arterial chemoembolization for subcapsular hepatocellular carcinoma.

BACKGROUND: I-125 seeds brachytherapy (ISB) has been used to improve the clinical effectiveness of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We aim to appraise the safety and clinical efficacy of combined ISB and TACE for the treatment of subcapsular HCC. MATERIALS AND METHODS: A retrospective investigative study extending from January 2017 to December 2020, involved individuals suffering from subcapsular HCC, who were subjected to TACE treatment with or without ISB in our center. The clinical effectiveness was compared between 2 groups. RESULTS: Sixty-four patients, in total, with subcapsular HCC had to undergo TACE with (n = 32) or without (n = 32) ISB in our center. After CT-guided ISB, only 2 (6.3%) patients experienced a self-limited pneumothorax. Combined treatment resulted in a significantly higher complete response (56.3% vs. 18.8%, P = 0.002) and total response (90.7% vs. 59.4%, P = 0.004) rates than that of TACE alone. In comparison to the TACE alone group, the median progression-free survival was substantially longer in the combined treatment group (11 months vs. 5 months, P = 0.016). Further, 15 and 28 patients in combined and TACE alone groups respectively died within the follow-up. The median OS was comparable between combined and TACE alone groups (22 months vs. 18 months, P = 0.529). CONCLUSIONS: Combined TACE and ISB therapy is a safe treatment method for individuals suffering from subcapsular HCC. When compared, combined treatment had significantly enhanced clinical efficacy as a subcapsular HCC therapy, in comparison to TACE alone.

Development of a model to predict recurrence after bronchial artery embolization for non-cancer related hemoptysis.

BACKGROUND: Relapse after effective bronchial arterial embolization (BAE) for controlling hemoptysis is not uncommon. Studies reported diverse predictors of recurrence. However, a model to assess the probability of recurrence in non-cancer related hemoptysis patients after BAE has not been reported. This study was to develop a model to predict recurrence after BAE for non-cancer related hemoptysis. METHODS: The study cohort included 487 patients who underwent BAE for non-cancer-related hemoptysis between January 2015 and December 2019. We derived the model's variables from univariate and multivariate Cox regression analyses. The model presented as a nomogram scaled by the proportional regression coefficient of each predictor. Model performance was assessed with respect to discrimination and calibration. RESULTS: One-month and 1-, 2-, 3- and 5-year recurrence-free rates were 94.5%, 88.0%, 81.4%, 76.2% and 73.8%, respectively. Risk factors for recurrence were underlying lung diseases and the presence of systemic arterial-pulmonary circulation shunts. This risk prediction model with two risk factors provided good discrimination (area under curve, 0.69; 95% confidence interval, 0.62-0.76), and lower prediction error (integrated Brier score, 0.143). CONCLUSION: The proposed model based on routinely available clinical and imaging features demonstrates good performance for predicting recurrence of non-cancer-related hemoptysis after BAE. The model may assist clinicians in identifying higher-risk patients to improve the long-term efficacy of BAE.

An updated meta-analysis of prostatic arterial embolization versus transurethral resection of the prostate in the treatment of benign prostatic hyperplasia.

OBJECTIVE: To investigate whether prostatic arterial embolization (PAE) could be recommended as a routine therapy for benign prostatic hyperplasia (BPH), we conducted an updated meta-analysis to assess the efficacy and safety of PAE compared with transurethral resection of the prostate (TURP). METHODS: Systematic literature retrieval by searching data from Web of science, Pubmed, Embase, Cochrane Library, ClinicalTrial.gov, CNKI, Wanfang and VIP databases was carried out to identify all related trials from the inception dates to June 2019. We also conducted subgroup analyses depending on the kind of study design, kind of PAE and kind of TURP. RESULTS: Nine studies comparing PAE with TURP involving a total of 860 BPH patients were selected. Postoperative reduced IPSS score (MD 2.50; 95% CI 0.78-4.21; P = 0.004), postoperative reduced QOL score (MD 0.40; 95% CI 0.09-0.71; P = 0.01), postoperative reduced PV (MD 8.59; 95% CI 4.74-12.44; P < 0.00001) and postoperative increased Qmax (MD 2.54; 95% CI 1.02-4.05; P = 0.001) were better in TURP than in PAE; however, PAE was associated with lower sexual dysfunction rate (OR 0.24; 95% CI 0.15-0.39; P < 0.00001) compared with TURP. Meanwhile, no significant difference in postoperative reduced PVR (MD 0.46; 95% CI - 2.08 to 3.00; P = 0.72) and complication (OR 0.57; 95% CI 0.21-1.55; P = 0.27) between PAE and TURP group was demonstrated. CONCLUSION: PAE was inferior to TURP in the improvement of postoperative IPSS, QOL, PV, Qmax and TURP still remained the gold standard. However, PAE may be a valuable alternative to TURP in the treatment of BPH patients who refuse surgery or with surgery contraindication.

Phenylpropanoid and Iridoid Glucosides from the Whole Plant of Hemiphragma heterophyllum and Their alpha-Glucosidase Inhibitory Activities.

Three phenylpropanoid glucosides (1:  - 3: ) and one iridoid glucoside (11: ), together with eleven known glucosides, were isolated from the ethanol extract of the whole plant of Hemiphragma heterophyllum. Their structures were elucidated by means of 1D and 2D NMR spectroscopy, HRMS, and chemical methods. All compounds except 11: and 13:  - 15: showed varying degrees of α-glucosidase inhibitory activity. Compounds 5, 9: , and 12: were marginally active in the bioassay, while compounds 1:  - 4: , 6:  - 8: , and 10: exhibited appreciable inhibitory activity with an IC50 value of 33.6 ~ 83.1 µM, which was much lower than that of the positive control acarbose (IC50 = 310.8 µM).

α-Glucosidase Inhibitory and Anti-Inflammatory Coumestans from the Roots of Dolichos trilobus.

Four new coumestans dolichosins A - D (1: -4: ) were isolated from the roots of Dolichos trilobus, together with four known compounds: isosojagol (5: ), phaseol (6: ), psoralidin (7: ), and 4″,5″-dehydroisopsoralidin (8: ). Their structures were elucidated on the basis of spectroscopic data interpretation, mass spectrometric analyses, and the comparison with literature data of related compounds. The anti-inflammatory activity of these compounds (1: -8: ) was evaluated through the inhibition of nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells, in which compounds 1: and 6: displayed moderate inhibitory activity and no cytotoxic effects. In a α-glucosidase inhibitory assay, compounds 1: and 5: -8: exhibited appreciable inhibition on α-glucosidase. Especially compounds 1, 7: , and 8: showed IC50 values lower than 20.0 µM.

Three new diterpenoids from Aralia dumetorum.

Three new diterpenoids, dumetoranes A (1) and B (2), melanocane B (3), together with four known ones including melanocane A (4), ent-15S,16-dihydroxypimar-8(14)-en-19-oic acid (5), ent-pimara-8(14),15-diene-19-oic acid (6), and ent-pimara-8(14),15-diene-19-ol (7) were obtained from the ethanol extract of the roots of Aralia dumetorum. Their structure elucidation was achieved by the methods of spectroscopic HRMS, IR, NMR, and by comparison with literature. The cytotoxicities of compounds 1-3 and 5 were assayed by in vitro MTT methods.

Chemical constituents from the whole herb of Hemiphragma heterophyllum.

Phytochemical investigation on Hemiphragma heterophyllum led to the isolation of two new compounds, heterophyllumin A (1) and heterophylliol (3), along with nine known compounds, (‒)-sibiricumin A (2), iridolactone (4), jatamanin A (5), dihydrocatalpolgenin (6), 25-hydroperoxycycloart-23-en-3ß-ol (7), 24-methylenecycloartanol (8), (+)-pinoresinol (9), hexadec-(4Z)-enoic acid (10), and 9,12, 15-octadecatrienoic acid (11). Their structures were elucidated on the basis of detailed spectroscopic analyses and by comparison with literature data. Further, the structure of compound 3 was unambiguously confirmed by single-crystal X-ray analysis. Some of those compounds showed moderate activity in the α-glucosidase inhibition assay.

[A new guaiane-type sesquiterpenoid from Croton yunnanensis].

Five sesquiterpenoids were isolated from 90% ethanol extract of Croton yunnanensis by silica gel,Sephadex LH-20 column chromatography,as well as prep-HPLC methods. Based on MS,1 D and 2 D NMR spectral analyses,the structures of the five compounds were identified as 11-methoxyl alismol(1),6ß,7ß-epoxy-4α-hydroxyguaian-10-ene(orientalol C,2),multisalactone D(3),arvestonol(4),and 4,5-dihydroblumenol A(5). Compound 1 was a new guaiane-type sesquiterpenoid. Compounds 2-4 were isolated from the Croton genus for the first time,and compound 5 was obtained from this plant for the first time.

Four New Diterpene Glucosides from Perovskia atriplicifolia.

Four new diterpene glucosides, namely perovskiaditerpenosides A - D (1 - 4), were isolated from the BuOH extract of Perovskia atriplicifolia. Their structures were well elucidated by chemical methods and comprehensive spectroscopic analyses including MS, IR, and NMR (1D and 2D). The newly isolated compounds were screened for their cytotoxic activity against HepG2, NB4, HeLa, K562, MCF7, PC3, and HL60. The obtained results indicated that the new compounds possessed considerable cytotoxic activity.

Cytotoxic Diterpenoids from the Roots of Aralia melanocarpa.

Five new diterpenoids (1-5) were isolated from the roots of Aralia melanocarpa, together with four known compounds, 7ß-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (6), 18-norpimara-8(14),15-dien-4-ol (7), ent-16ßH,17-isovalerate-kauran-19-oic acid (8), and ent-16α,17-dihydroxykauran-19-oic acid (9). Based on the MS, IR, and NMR spectral analysis, the structures of the five new diterpenoids (1-5) were elucidated. The cytotoxic activities of compounds 1-9 were assayed, and compounds 1 and 2 showed cytotoxicity in four cancer cell lines with IC50s from 4.2 to 8.2 µM.

Icetexane diterpenoids from Perovskia atriplicifolia.

Five new icetexane diterpenoids, namely, perovskatones B-D (1, 3, 4), 1α-hydroxybrussonol (2), and 1α-hydroxypisiferanol (5), were isolated from Perovskia atriplicifolia, together with a new natural product (6) and two known compounds, przewalskin E (7) and brussonol (8). The structures of the new compounds were elucidated by detailed analyses of their MS, IR, 1D, and 2D NMR data. Compounds 1-8 were assayed for their inhibitory hepatitis B virus activities in the HepG 2.2.15 cell line. The results suggested that compounds 1 and 2 possessed noticeable anti-hepatitis B virus activity in vitro, suppressing the replication of hepatitis B virus DNA with selectivity index values of 154.3 and 137.7, respectively.

[Chemical constituents from Perovskia atriplicifolia].

An investigation on the chemical constituents of the 90% EtOH extract of Perovskia atriplicifolia led to the isolation of fifteen compounds from the EtOAc fraction. Based on the detailed spectral analysis (MS, 1D and 2D NMR), as well as comparison with the literatures, the structures of compounds 1-15 were determined as cirsimaritin (1), salvigenin (2), syringaldehyde (3), vinyl caffeate (4), 2α, 3α-dihydroxyolean-12-en-28-oicacid (5), 2α, 3α-dihydroxyurs-12-en-28-oicacid (6), niga-ichigoside F1 (2α, 3ß, 19α, 23- tetrahydroxyurs - 12-en-28-oicacid- O-ß-D- glucopyranoside, 7), sericoside (8), 4-epi-niga-ichigoside F1 (2α, 3ß, 19α, 24-tetrahydroxyurs-12-en-28-oicacid O-ß-D-glucopyranoside, 9), 2α, 3ß, 24-trihydroxyolean-12-en-28-oicacid O-ß-D-glucopyranosyl-(1 --> 2) - ß-D-glucopyranoside (10), pruvuloside A (11), asteryunnanoside A [2α, 3ß, 23-trihydroxyolean-12-en-28-oicacid O-ß-D-glucopyranosyl-(1 --> 2)-ß- D- glucopyranoside,12], rosmarinic acid methyl ester (13), ß-sitosterol (14), and daucosterol (15), respectively. Compounds 1-13 were isolated from the Perovskia genus for the first time. All the compounds were obtained from P. atriplicifolia for the first time.

New clerodane diterpenes from Tinospora sagittata var. yunnanensis.

Four new clerodane diterpenes, namely sagittatayunnanosides A-D (1-4), were isolated from the roots of Tinospora sagittata var. yunnanensis, together with two known compounds, tinospinoside C (5) and tinospinoside E (6). The structures of the four new compounds were well elucidated by extensive analyses of the MS, IR, and 1D and 2D NMR data. The cytotoxic and antifouling activities of compounds 1-6 were evaluated.

Nontoxic piperamides and their synthetic analogues as novel antifouling reagents.

Bioassay-guided isolation of an acetone extract from a terrestrial plant Piper betle produced four known piperamides with potent antifouling (AF) activities, as evidenced by inhibition of settlement of barnacle cypris larvae. The AF activities of the four piperamides and 15 synthesized analogues were compared and their structure-activity relationships were probed. Among the compounds, piperoleine B and 1-[1-oxo-7-(3',4'-methylenedioxyphenyl)-6E-heptenyl]-piperidine (MPHP) showed strong activity against settlement of cyprids of the barnacle Balanus amphitrite, having EC50 values of 1.1 ± 0.3 and 0.5 ± 0.2 µg ml(-1), respectively. No toxicity against zebra fish was observed following incubation with these two compounds. Besides being non-toxic, 91% of piperoleine B-treated cyprids and 84% of MPHP-treated cyprids at a concentration of 100 µM completed normal metamorphosis in recovery bioassays, indicating that the anti-settlement effect of these two compounds was reversible. Hydrolysis and photolysis experiments indicated that MPHP could be decomposed in the marine environment. It is concluded that piperamides are promising compounds for use in marine AF coatings.

The antinociceptive and anti-alpha-glucosidase effects of glucosides from Hemiphragma heterophyllum Wall.

Hemiphragma heterophyllum Wall. is commonly used in traditional Yi herbal medicine for treating bellyache and toothache. In the current study, an unreported monoterpene glucoside, (S)-thymoquinol O-(6-O-oleuropeoyl)-ß-d-glucopyranoside (1), together with 11 known glucosides were obtained from the whole herb of H. heterophyllum. Their structures were determined based on a detailed analysis of spectroscopic data and acid hydrolysis and methanolysis reactions. Bioassay results showed that compounds 1 and 10 at 40 mg/kg exhibited significant antinociceptive activity in the acetic acid-induced writhing model, with inhibitions of 59.80% and 64.07%, respectively. Moreover, five of the isolates showed moderate anti-α-glucosidase activities with IC50 values ranging from 5.67 to 46.16 µM.

Cytotoxic oxepinochromenone and flavonoids from the flower buds of Rosa rugosa.

A new oxepinochromenone, rugosachromenone A (1), seven new flavonoids, rugosaflavonoids A-G (2-8), and 11 known compounds (9-19) were isolated from the flower buds of Rosa rugosa. Compound 1 is found from Nature for the first time. Compound 2 displayed cytotoxicity against NB4, SHSY5Y, and MCF7 cells with IC50 values of 2.2, 2.5, and 2.3 µM, respectively, and 3 was toxic to A549 and MCF7 cells with IC50 values of 1.2 and 2.8 µM, respectively.

Cytotoxic deoxybenzoins and diphenylethylenes from Arundina graminifolia.

Eight new C-4-alkylated deoxybenzoins (1-8), three new diphenylethylenes (9-11), and five known diphenylethylenes were isolated from Arundina graminifolia. The structures of 1-11 were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. Compounds 9-11 are the first naturally occurring diphenylethylenes possessing a hydroxyethyl unit. Compounds 1-11 were evaluated for cytotoxicity against five human tumor cell lines. Compounds 4, 5, and 9-11 showed significant cytotoxicity against five cancer cell lines, with IC50 values ranging from 1.8 to 8.7 µM.

Cytotoxic flavanes from Uraria clarkei.

Two new flavanes, (2R)-4'-hydroxy-2',5,7-trimethoxyflavane (1) and (2R,4R)-2',4'-dihydroxy-5,7-dimethoxyflavan-4-ol (2), were isolated from Uraria clarkei, together with two known compounds 5,7-dimethoxy-4'-hydroxyflavan (3) and 5,7,4'-trimethoxyflavan (4). The structures of the new flavanes were characterized by analyses of the MS, IR, UV, CD, 1D, and 2D NMR data. Cytotoxicity test suggested that compounds 1-4 possessed slight activity against K-562 and Hela cell lines, with the IC50 values ranging from 26.6 to 56.3 µM.

Two new sphingolipids from the leaves of Piper betle L.

Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

The combined analgesic, sedative, and anti-gastric cancer mechanisms of Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo based on integrated ethnopharmacological data.

ETHNOPHARMACOLOGY RELEVANCE: As a Yi medicine for eliminating wind to relieve pain, Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo (TSY) is widely used to treat sore throat, stomach pain, bone and muscle injuries, and tumors; however, the material basis and mechanism of action remain unclear. AIM OF THE STUDY: This study aims to investigate the potential active compounds of TSY and related pharmacological mechanisms against gastric cancer using a multitarget strategy. MATERIALS AND METHODS: The main chemical components of TSY were collected through a literature review and database searches. The components were further screened for ADMET properties, and their targets were predicted using network pharmacology (admetSAR) and substructure-drug-target network-based inference (SDTNBI) approaches in silico. The pharmacological mechanism of action of TSY extract for pain relief, sedation, and anti-gastric cancer activities were identified via in vivo and in vitro biochemical analyses. RESULTS: Here, 28 chemical components were identified, 7 active compounds were selected, and 75 targets of TSY extract were predicted. A compound-target-disease network topological approach revealed that the predicted targets are highly related to the digestive system and nervous system. Network pharmacology results suggested that the anti-gastric cancer activity of TSY was highly correlated with its analgesic and sedative targets and MAPK. In vivo experiments confirmed that TSY extract not only reduced the number of voluntary activities in the mouse model but also exhibited a synergistic effect on sodium pentobarbital-induced sleep, reduced the number of mice exhibiting writhing responses to acetic acid, and increased the hot plate pain threshold of mice. Thus, TSY extract exhibits good analgesic and sedative effects. The TSY extract inhibited HGC-27 cell proliferation and induced apoptosis by regulating apoptotic proteins (BAX, BCL-2 and BCL-XL) in vitro. CONCLUSIONS: TSY exhibits combined analgesic, sedative, and anti-gastric cancer activities.