Diagnostic efficiency of conventional ultrasound, shear wave elastography, and superb microvascular imaging in evaluating ulnar neuropathy at the elbow.

INTRODUCTION/AIMS: The current diagnosis of ulnar neuropathy at the elbow (UNE) relies mainly on the clinical presentation and nerve electrodiagnostic (EDX) testing, which can be uncomfortable and yield false negatives. The aim of this study was to investigate the diagnostic value of conventional ultrasound, shear wave elastography (SWE), and superb microvascular imaging (SMI) in diagnosing UNE. METHODS: We enrolled 40 patients (48 elbows) with UNE and 48 healthy volunteers (48 elbows). The patients were categorized as having mild, moderate or severe UNE based on the findings of EDX testing. The cross-sectional area (CSA) was measured using conventional ultrasound. Ulnar nerve (UN) shear wave velocity (SWV) and SMI were performed in a longitudinal plane. RESULTS: Based on the EDX findings, UNE severity was graded as mild in 4, moderate in 10, and severe in 34. The patient group showed increased ulnar nerve CSA and stiffness at the site of maximal enlargement (CSA mean at the site of max enlargement [CSAmax] and SWV mean at the site of max enlargement [SWVmax]), ulnar nerve CSA ratio, and stiffness ratio (elbow-to-upper arm), compared with the control group (p < .001). Furthermore, the severe UNE group showed higher ulnar nerve CSAmax and SWVmax compared with the mild and moderate UNE groups (p < .001). The cutoff values for diagnosis of UNE were 9.5 mm2 for CSAmax, 3.06 m/s for SWVmax, 2.00 for CSA ratio, 1.36 for stiffness ratio, and grade 1 for SMI. DISCUSSION: Our findings suggest that SWE and SMI are valuable diagnostic tools for the diagnosis and assessment of severity of UNE.

Periostin Promotes the Proliferation, Differentiation and Mineralization of Osteoblasts from Ovariectomized Rats.

Perimenopausal period causes a significant amount of bone loss, which results in primary osteoporosis (OP). The Periostin (Postn) may play important roles in the pathogenesis of OP after ovariectomized (OVX) rats. To identify the roles of Postn in the bone marrow mesenchymal stem cell derived osteoblasts (BMSC-OB) in OVX rats, we investigated the expression of Wnt/ß-catenin signaling pathways in BMSC-OB and the effects of Postn on bone formation by development of BMSC-OB cultures. Twenty-four female Sprague-Dawley rats at 6 months were randomized into 3 groups: sham-operated (SHAM) group, OVX group and OVX+Postn group. The rats were killed after 3 months, and their bilateral femora and tibiae were collected for BMSC-OB culture, Micro-CT Analysis, Bone Histomorphometric Measurement, Transmission Electron Microscopy and Immunohistochemistry Staining. The dose/time-dependent effects of Postn on the proliferation, differentiation and mineralization of BMSC-OB and the expression of osteoblastic markers were measured in in vitro experiments. We found increased Postn increased bone mass, promoted bone formation of trabeculae, Wnt signaling and the osteogenic activity in osteoblasts in sublesional femur. Postn have the function to enhance cell proliferation, differentiation and mineralization at a proper concentration and incubation time. Interestingly, in BMSC-OB from OVX rats treated with the different dose of Postn, the osteoblastic markers expression and Wnt/ß-catenin signaling pathways were significantly promoted. The direct effect of Postn may lead to inhibit excessive bone resorption and increase bone formation through the Wnt/ß-catenin signaling pathways after OVX. Postn may play a very important role in the pathogenesis of OP after OVX.

Synthesis and biological evaluation of lycoctonine derivatives with cardiotonic and calcium channels inhibitory activities.

In our previous study, a screening of a variety of lycotonine-type diterpenoid alkaloids were screened for cardiotonic activity revealed that lycoctonine had moderate cardiac effect. In this study, a series of structurally diverse of lycoctonine were synthesized by modifying on B-ring, D-ring, E-ring, F-ring, N-atom or salt formation on lycoctonine skeleton. We evaluated the cardiotonic activity of the derivatives by isolated frog heart, aiming to identify some compounds with significantly enhanced cardiac effects, among which compound 27 with a N-isobutyl group emerged as the most promising cardiotonic candidate. Furthermore, the cardiotonic mechanism of compound 27 was preliminarily investigated. The result suggested that the cardiotonic effect of compound 27 is related to calcium channels. Patch clamp technique confirmed that the compound 27 had inhibitory effects on CaV1.2 and CaV3.2, with inhibition rates of 78.52 % ± 2.26 % and 79.05 % ± 1.59 % at the concentration of 50 µM, respectively. Subsequently, the protective effect of 27 on H9c2 cells injury induced by cobalt chloride was tested. In addition, compound 27 can alleviate CoCl2-induced myocardial injury by alleviating calcium overload. These findings suggest that compound 27 was a new structural derived from lycoctonine, which may serve as a new lead compound for the treatment of heart failure.

Diterpenoid Alkaloids from Delphinium liangshanense.

Two new C19-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of Delphinium liangshanense W. T. Wang, and all the compounds were identified by different spectroscopic analyses, such as IR, HR-ESI-MS and NMR. All the compounds were isolated from this plant for the first time and tested for the anti-proliferation effects on MH7 A and SF9 cells to figure their anti-rheumatoid arthritis and anti-insect activity, but none of them showed remarkable activity.

In vitro and in†vivo biological evaluation of Lappaconitine derivatives as potential anti-inflammatory agents.

Natural products and their derivatives are a precious treasure in the pursuit of potent anti-inflammatory drugs. In this work, we measured the toxicity of 78 LA derivatives at 20 µM using MTT, then we evaluated the NO release of compounds without obvious toxicity in LPS-induced RAW.264.7 by Griess reagent, we identified three compounds, namely compounds 6, 19, 70, which exhibited promising anti-inflammatory potential. These compounds exhibited IC50 values of 10.34±2.05 µM, 18.18±4.80 µM and 15.66±0.88 µM. In addition, through ELISA kits, compounds 6, 19, 70 significantly reduce the production of inflammatory factors (TNF-α, IL-6, IL-1ß). Real-time PCR and western blot analysis showed that compounds 6, 19, 70 inhibited the mRNA and protein expression of iNOS and COX-2. Notably, compound 6 exhibited the most potent inhibitory activity. In vitro, it inhibits LPS-induced phosphorylation of NF-κB p65, IκBα, ERK1/2, JNK, and p38 MAPKs in RAW264.7 cells. In vivo, compound 6 potently inhibits the secretion of inflammatory mediators and neutrophil activation in ALI mice. Our findings suggest that compound 6 may be a potential anti-inflammatory drug.

Diterpenoid alkaloids from Delphinium sherriffii.

Three new diterpenoid alkaloids (1, 2, 3) and seventeen known (4-20) compounds were isolated from the whole plant of Delphinium sherriffii Munz (Ranunculaceae). Their structures were elucidated by various spectroscopic analyses, including IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were evaluated for the inhibitory activity of Sf9 cells and compound 5 exhibited the strongest cytotoxicity (IC50 = 8.97 µM) against Sf9 cell line.

Impacts of continuous quality improvement on wound pain in the puncture site of arteriovenous fistula in haemodialysis patient.

This study analyses the effects of a continuous quality improvement nursing model on wound pain at the arteriovenous fistula (AVF) puncture site in patients undergoing haemodialysis. Forty haemodialysis patients from the First Affiliated Hospital of Chongqing Medical University, from September 2020 to December 2022, were selected as study subjects. They were randomly divided into an observation group and a control group. The control group received conventional nursing care, while the observation group was treated with a continuous quality improvement nursing model. The study compared the impact of these nursing approaches on pain intensity post-AVF puncture, wound visual analogue scale scores, self-rating anxiety scale, self-rating depression scale, quality of life scores and patient satisfaction with nursing care. In the observation group, the proportion of patients experiencing moderate to severe pain during AVF puncture was lower than that in the control group, whereas the proportion of patients with no pain or mild pain was higher (P = 0.008). After nursing, the observation group exhibited significantly lower wound visual analogue scale scores, self-rating anxiety scale scores, and self-rating depression scale scores compared to the control group (P < 0.001), with a significantly higher quality of life score (P < 0.05). The nursing satisfaction rate was 95.00% in the observation group, significantly higher than the 65.00% in the control group (P = 0.018). The continuous quality improvement nursing model significantly reduces wound pain at the AVF puncture site in haemodialysis patients, alleviates negative emotions, enhances the quality of life, and achieves high patient satisfaction. It is thus a highly recommendable approach in nursing practice.

Photochemical Selective Oxidation of Benzyl Alcohols to Aldehydes or Ketones.

Using Eosin Y as a metal-free photocatalyst and O2 as an oxidant, the present study reports a new photochemical protocol that enables efficient aerobic oxidation of various benzyl alcohols to the corresponding aldehydes or ketones in excellent yields under mild reaction conditions. The catalyst system presents good functional-group tolerance and exquisite chemoselectivity, which also can easily be scaled-up to gram scale. Moreover, the methodological applications in practical synthesis of several organic molecules and the primary reaction mechanism were also discussed.

Palladium-Catalyzed Synthesis, Acetylcholinesterase Inhibition, and Neuroprotective Activities of N-Aryl Galantamine Analogues.

A series of new N-aryl galantamine analogues (5a-5x) were designed and synthesized by modification of galantamine, using Pd-catalyzed Buchwald-Hartwig cross-coupling reaction in good to excellent yields. The cholinesterase inhibitory and neuroprotective activities of N-aryl derivatives of galantamine were evaluated. Among the synthesized compounds, the 4-methoxylpyridine-galantamine derivative (5q) (IC50 = 0.19 µM) exhibited excellent acetylcholinesterase inhibition activity, as well as significant neuroprotective effect against H2O2-induced injury in SH-SY5Y cells. Molecular docking, staining, and Western blotting analyses were performed to demonstrate the mechanism of action of 5q. Derivative 5q would be a promising multifunctional lead compound for the treatment of Alzheimer's disease.

Synthesis, antiproliferative and anti-MDR activities of lathyrane diterpene derivatives based on configuration inversion strategy.

A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3ß) were synthesized from natural rich Euphorbia factor L3via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 µM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 µM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed.

Metabolite Profiling of Talatisamine in Heart Tissue After Oral Administration and Analysis of Cardiac Bioactivities.

The lateral roots of the Aconitum carmichaelii ("Fuzi") have been used for centuries as a cardiotonic in China. The diterpenoid alkaloid talatisamine (TA) is a major bioactive component of Fuzi, but the identity and bioactivities of the TA metabolites have not been examined in detail. In this study, metabolite profiling of TA was performed in rat heart by UPLC-MS following oral administration. Metabolites were identified by comparing protonated molecules, fragmentation patterns, and chromatographic behaviors with those of standard compounds. Metabolites of TA were then prepared and tested for cardiotonic activity on isolated frog hearts. The metabolite cammaconine, a C19 diterpenoid alkaloid with a hydroxyl group at C-18, exhibited substantial cardiotonic activity during frog heart perfusion. To further investigate the structure-cardiac effect relationships, a series of C19-diterpenoid alkaloids with 18-OH were prepared. Eight tested compounds (5: -12: ) demonstrated measurable cardioactivity, of which compound 5: with an N-methyl group and compound 7: with a methoxy at C-16 showed stronger effects on ventricular contraction than the other compounds. Thus, 18-OH is a critical structural feature determining cardiotonic activity, and efficacy is improved by the presence of N-methyl or methoxy at C-16. Preliminary mechanistic studies suggested that the cardiotonic effect of compound 5: is mediated by enhanced cellular calcium influx. Metabolites of TA with these structural features may be useful therapeutics to prevent heart failure.

Four New C19 -Diterpenoid Alkaloids from Aconitum nagarum Stapf.

Four new aconitine-type C19 -diterpenoid alkaloids, were isolated from the roots of Aconitum nagarum Stapf which were named as nagarutines A-D (1-4), together with eleven known compounds (5-15). The structures of the compounds were identified by IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were tested for the inhibitory effect on LPS induced NO production in RAW 264.7 macrophages, compound 7 showed moderate anti-inflammatory activity effect and Inhibition rate is about 44.50%.

A new oleanane-type triterpenoid saponin with α-glucosidase inhibitory activity from Camellia nitidissima.

A new oleanane-type triterpenoid saponin, 21ß, 22α-di-O-angeloyl-15α, 16α, 28-trihydroxyolean-12-ene 3ß-O-α-L-rhamnopyranosyl-(1→3)-α-D-xylopyranosyl-(1→3)-ß-D-glucopyranoside (1), together with five known compounds (2-5), were isolated from Camellia nitidissima. Their structures were elucidated based on spectroscopic methods, including extensive NMR and MS spectra. Compound 1 showed potential inhibitory activity on α-glucosidase with the IC50 values of 185.9 ± 44.5 µmol/L.

Two new dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus.

Two undescribed dammarane triterpenoid saponins, cypaliurusides O and P (1 and 2), were isolated from the ethanol extracts of the leaves of Cyclocarya paliurus. Bioactivity assay results showed that compound 1 has potential cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 14.55 ± 0.55 to 22.75 ± 1.54 µM. Compound 1 showed better antitumor activity against HepG2 cells with IC50 of 14.55 ± 0.55 µM. In addition, compound 2 showed no obvious antitumor activity.

Diterpenoid alkaloids from two species of Delphinium.

Four new compounds (1-4) were isolated from the whole plants of two species of Delphinium, including two C20-diterpenoid alkaloids, umbrodines A and B (1 and 2), and a dibenzoxazepinone, umbrolide A (3) from Delphinium umbrosum Hand.-Mazz. and a C20-diterpenoid alkaloid, kingiadine (4) from Delphinium kingianum Bruhl. ex Huth. Ten known diterpenoid alkaloids were also isolated. Their structures were elucidated via HR-ESIMS, IR, and NMR data. Lycoctonine (11) and delectinine (12) exhibited appreciable cardiac activity. Furthermore, 11 and 12 showed cardioprotective effects against doxorubicin-induced toxicity in H9c2 cells, with the maximum protection rates of 61.63% and 51.18%, respectively.

Compounds isolated from the pericarp of Zanthoxylum bungeanum and inhibitory activity against LPS-induced NO production in RAW264.7.

Seventeen compounds were isolated and identified from the ethyl acetate part of Zanthoxylum bungeanum Maxim., including one new compound 18-acetyloxyneocryptotanshinone (1) and 16 known compounds (2-17). Their structures were elucidated by extensive spectroscopy. The absolute configuration of 1 was confirmed by electronic circular dichroism (ECD). All compounds were evaluated for the inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, of which 1 and 10 exhibited the most significant inhibitory effect, with IC50 of 17.29 and 10.27 µM, respectively.

Diterpenoid alkaloids from Delphinium trichophorum.

Three new hetisine type C20-diterpenoid alkaloids, named as trichophorines A-C (1-3), were isolated from Delphinium trichophorum, together with nine known alkaloids (4-12). Their structures were elucidated on the basis of spectroscopic data (1D, 2D NMR, single-crystal X-ray, and HR-ESI-MS). All compounds were evaluated for the inhibitory activities against LPS induced NO production in RAW 264.7 macrophage cells, and none of them showed considerable inhibitory activity.

Synthesis and Biological Evaluation of Novel 2-Amino-1,4-Naphthoquinone Amide-Oxime Derivatives as Potent IDO1/STAT3 Dual Inhibitors with Prospective Antitumor Effects.

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC50 = 0.06 µM), leading to its selection for further investigation. The direct interactions between compound NK3 and IDO1 and STAT3 proteins were confirmed through surface plasmon resonance analysis. A molecular docking study of compound NK3 revealed key interactions between NK3 and IDO1, with the naphthoquinone-oxime moiety coordinating with the heme iron. In the in vitro anticancer assay, compound NK3 displayed potent antitumor activity against selected cancer cell lines and effectively suppressed nuclear translocation of STAT3. Moreover, in vivo assays conducted on CT26 tumor-bearing Balb/c mice and an athymic HepG2 xenograft model revealed that compound NK3 exhibited potent antitumor activity with low toxicity relative to 1-methyl-L-tryptophan (1-MT) and doxorubicin (DOX). Overall, these findings provided evidence that the dual inhibitors of IDO1 and STAT3 may offer a promising avenue for the development of highly effective drug candidates for cancer therapy.

Synthesis and biological evaluation of esculetin derivatives as potential anti-HBV agents.

Previous in vivo and in vitro studies revealed that esculetin (Fig. 1) has anti-hepatitis B virus (anti-HBV) activity as well as a protective effect on liver damage caused by duck hepatitis B virus. We designed and synthesized a series of esculetin derivatives, introduced side chains containing various amino groups into site 7 of the parent structure, and synthesized C-4 and C-8 substituted derivatives with the goal of investigating their anti-HBV activities. In vitro anti-HBV activity was performed against HepG2.2.15 cells by using Enzyme-Linked Immunosorbent Assay(ELISA) kit and cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay with lamivudine as the positive control. The results demonstrated that several compounds showed moderate anti-HBV activity, while the introduction of morpholine groups could significantly inhibit the expression of hepatitis B e antigen (HBeAg) and the introduction of the 2-methylimidazole group could significantly inhibit the expression of Hepatitis B surface antigen (HBsAg). Among all tested compounds, compound 4a demonstrated the best anti-HBeAg activity (IC50 = 15.8 ± 4.2 µM), while compound 6d demonstrated the best anti-HBsAg activity (IC50 = 21.4 ± 2.8 µM). Compounds 6b and 6c showed moderate anti-HBV activity and HBsAg inhibition. Compounds 4b showed moderate anti-HBV activity and an inhibitory effect on HBeAg. In addition, compounds 4a, 4c, 4d, 6b, 6c and 6d showed improved metabolic stability. This study provides useful guidance for the discovery of anti-HBV drugs, which merits further investigation.

Adenophorone, An Unprecedented Sesquiterpene from Eupatorium adenophorum: Structural Elucidation, Bioinspired Total Synthesis and Neuroprotective Activity Evaluation.

(-)-Adenophorone (1), a caged polycyclic sesquiterpene featuring an unprecedented tricyclo[4.3.1.05,9 ]decane skeleton, was isolated from Eupatorium adenopharum Spreng. The structure of 1 was unambiguously established by a combination of spectroscopic analysis, X-ray crystallography, and bioinspired total synthesis. Key synthetic features include a sequential Reformatsky/oxidation/regio- and stereoselective hydrogenation, and subsequent merged MBH-Tsuji-Trost cyclization. The concise synthetic sequence efficiently constructs the bicyclic skeleton of cadinene sesquiterpene (+)-euptox A (2) in 8 steps from commercially available monoterpene (-)-carvone (6), with outstanding performance on diastereocontrol. The bioinspired synthesis of 1 was achieved from 2, a plausible biogenetic precursor, via transannular Michael addition. This work provides experimental evidence of our proposed biosynthetic hypothesis of 1. Additionally, compound 1 showed potent neuroprotective activity in H2 O2 -treated SH-SY5Y and PC12 cells.