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1.
Dalton Trans ; 53(20): 8803-8811, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38716557

ABSTRACT

Two photochromic Cd(II)-CPs were obtained based on the viologen ligand using different synthetic routes, named {[Cd4(p-BDC)4(CPB)2(H2O)2]·2H2O·EtOH}n (1) and {[Cd(p-BDC)(CPB)(H2O)]·(L)·DMF}n (2) (p-H2BDC = 1,4-benzene-dicarboxylate, HCPB·Cl = 1-(4-carboxyphenyl)-4,4'-bipyridinium·Cl, L = 2,4-dinitrochlorobenzene, and DMF = N,N-dimethylformamide), respectively. Due to different coordination modes, the two Cd(II)-CPs show different structures. Compound 1 exhibits a three-dimensional (3D) framework with bimetallic nodes, while compound 2 displays a 2-fold interpenetrated (4,4) net topology. Notably, the two Cd(II)-CPs exhibit substantial disparities in photo/thermochromism, which can be attributed to variations in donor-acceptor (D-A) distances arising from structural differences. Compound 1 showed visually sensitive photo- and thermochromic behavior due to multi-pathway electron transfer and short D-A distances, which is relatively rare in electron-transfer type photochromic systems. In contrast, 2 only demonstrates insensitive photochromic behavior, with a slight deepening of the color observed after 2 hours of UV light, which is due to the mono-pathway electron transfer and long D-A distance. Moreover, we first combined Cd(II)-viologen CPs with polydimethylsiloxane (PDMS) to prepare a 1@PDMS flexible UV imaging film. 1@PDMS exhibits excellent bendability and stretchability and maintains good photochromic properties after 100 bending cycles. To demonstrate the rapid color response and distinct color contrast of 1, its application in anti-counterfeiting is also demonstrated.

2.
AIDS ; 38(6): 803-812, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38578958

ABSTRACT

OBJECTIVES: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH. METHODS: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. RESULTS: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. CONCLUSION: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.


Subject(s)
Anti-HIV Agents , HIV Infections , Middle Aged , Aged , Humans , HIV Infections/drug therapy , Anti-HIV Agents/adverse effects , China , Treatment Outcome , CD4 Lymphocyte Count , Viral Load
3.
Dalton Trans ; 53(11): 5192-5201, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38381164

ABSTRACT

Smart chromic materials reacting to physicochemical stimuli are widely applied in optical switches, smart windows, and chemical sensors. Currently, most materials only respond to a single stimulus, but those that respond to multiple external stimuli are still in the minority. Herein, we report a novel porous zinc tungstate@metaloxoviologen framework [Zn3(Bcbpy)6(H2O)2]-[ZnW12O40]·6H2O (ZnW12@MV, H2BcbpyCl2 = 1,1'-bis(3-carboxybenzyl)-4,4'-bipyridinium dichloride), which shows multiple stimulus-responsive properties due to a combination of different functional motifs, namely, viologen electron acceptors, luminescent zinc-oxygen-clusters, porous cationic frameworks, and ZnW12O406- electron donors. Generally, the large-sized polyoxometalate (POM) anions serving as structure-directing agents can easily direct the formation of the oligomeric metaloxoviologen cations, mainly because POMs may break down some linkages leaving larger spaces for themselves. The large ZnW12O406- anions in ZnW12@MV are encapsulated into three-dimensional (3D) metaloxoviologen frameworks built up from the linkages of trinuclear zinc-oxygen clusters and Bcbpy viologens, which offer the first example of a 3D metaloxoviologen framework induced by large-sized POM anions. ZnW12@MV shows a reversible chromic response to X-ray/UV and electricity via different stimulus-induced electron transfers between electron-rich POM anions and electron-deficient metaloxoviologen frameworks, whereas the coloration changes are ascribed to the formation of radical and mixed-valence colored state ZnW12O406- species. The photochromic behavior is accompanied by photoluminescence quenching. The discriminative response to different-sized amines is attributed to the formation of viologen radicals through host-guest electron transfer. These results indicate that the multi-stimulus response ZnW12@MV can be applied in electrochromic devices, inkless erasable printing, and the detection of amines.

4.
Eur J Med Chem ; 264: 115996, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38086195

ABSTRACT

Mitochondria, responsible for ATP production and apoptosis regulation, play a key role in cancer cells. Honokiol regulates apoptosis through the endogenous mitochondrial pathway but does not specifically target tumor cells. We designed 28 novel derivatives of honokiol using triple-function delocalized lipophilic cations such as berberine and F16 as mitochondrion-targeting carriers. While all derivatives exhibited enhanced cytotoxicity toward tumor cells compared to honokiol, the derivative 2E-3-F16 exhibited a substantial tumor cell selectivity between NCI-H446 cancer cells and HBE cells by one order of magnitude and enhanced the sensitivity of A549 cells to cisplatin. Mechanistically, it targeted mitochondria and induced apoptosis by preventing tumor cells from entering the G0/G1 phases as well as inducing an abnormal elevation of reactive oxygen species, thereby decreasing the mitochondrial membrane potential level. It also showed lower toxicity toward Caenorhabditis elegans than honokiol. This study provides a possible method for developing mitochondrion-targeting antitumor drugs with high efficiency and low toxicity based on natural products.


Subject(s)
Antineoplastic Agents , Lignans , Animals , Caenorhabditis elegans , Antineoplastic Agents/pharmacology , Apoptosis , Lignans/pharmacology , Biphenyl Compounds/pharmacology , Cell Line, Tumor
5.
Article in English | MEDLINE | ID: mdl-37515912

ABSTRACT

Traditional Chinese medicine (TCM) is characterized by its multiple components. The utilization of mathematical statistical methods to integrate the pharmacokinetics of monomer components can provide a comprehensive understanding of the holistic pharmacokinetic process of TCM. Two distinct integrated methods, namely the correlation coefficient method and the AUC-based weight coefficient method, were employed in this study to elucidate and compare their differences in the integrated pharmacokinetic research of Fangji Huangqi decoction (FHD). FHD is commonly used in clinical practice to treat the nephrotic syndrome. Firstly, one-dose FHD was given to doxorubicin-induced nephropathy (DN) rats, and the prototype compounds of FHD and their metabolites in plasma were qualitatively and semi-quantitatively analyzed by UHPLC-MS/MS. Secondly, the efficacy of FHD was quantitatively characterized by the relative distance method based on metabolomics. The correlation coefficients were obtained by analyzing the correlation between efficacy (relative distance values) and the content of compound, and they were subsequently used for the model integration (correlation coefficient method). Thirdly, the effective compounds of FHD treating DN were screened by integrating network pharmacology and molecular docking, and they were used for another integrated pharmacokinetic model by AUD-based weight coefficient method. Finally, the 2 integrated methods and the 2 integrated pharmacokinetic models were compared. In this study, 30 prototype compounds and 41 metabolites of FHD in plasma were identified, and the pharmacokinetic curve of 18 prototype compounds were built. The efficacy of FHD in the treatment of DN has been relatively quantitation. The 2 established integrated pharmacokinetic models of FHD indicated that the correlation coefficient method was the optimal approach for conducting the integrated pharmacokinetic research on the TCM with unknown effective compounds, whereas the AUC-based coefficient method was suitable for the TCM with the clear effective compounds. The integrated pharmacokinetic models indicated that FHD had high bioavailability and an absorption peak at about 6 h after administration, indicating that the 6 h after administration was the critical period of FHD treating DN. This research would be helpful for the pharmacological and pharmacokinetic research of FHD, and provide a method reference for the integrated pharmacokinetic research of TCM.


Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Animals , Rats , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional/methods , Molecular Docking Simulation , Tandem Mass Spectrometry/methods
6.
Bioorg Chem ; 139: 106714, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37454496

ABSTRACT

The pathogenesis of Alzheimer's disease (AD), a multifactorial progressive neurodegenerative disease associated with aging, is unclear. Ethyl caffeate is a plant polyphenol that has been reported to have neuroprotective effects, but the mechanisms by which it acts are unclear. In this study, for the first time, we investigated the molecular mechanism of its anti-AD properties using the Caernorhabditis elegans model. The results of our experiments showed that ethyl caffeate delayed the paralysis symptoms of CL4176 to a different extent and reduced the exogenous 5-hydroxytryptophan-induced paralysis phenotype. Further studies revealed that ethyl caffeate lowered Aß plaques and depressed the expression of Aß monomers and oligomers, but did not influence the mRNA levels of Aß. Moreover, it was able to bring paraquat-induced ROS levels down to near-standard conditions. Real-time quantitative PCR experiment showed a significant upregulation of the transcript abundance of daf-16, skn-1 and hsf-1, key factors associated with the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway (IIS), and their downstream genes sod-3, gst-4 and hsp-16.2. It was further shown that ethyl caffeate activated the translocation of DAF-16 and SKN-1 from the cytoplasm to the nucleus and enhanced the expression of sod-3::GFP, gst-4::GFP and hsp-16.2::GFP in transgenic nematodes. This meant that the protection against Aß toxicity by ethyl caffeate may be partly through the IIS signaling pathway. In addition, ethyl caffeate suppressed the aggregation of polyglutamine proteins in AM141, which indicated a potential protective effect against neurodegenerative diseases based on abnormal folding and aggregation of amyloid proteins. Taken together, ethyl caffeate is expected to develop as a potential drug for the management of AD.

7.
Phytochemistry ; 211: 113686, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37105352

ABSTRACT

The entire plant Salvia cavaleriei H.Lév. (Lamiaceae) is used as a traditional Chinese herbal medicine. Its leaves are edible, and the flowers can be soaked in water to make a health-care tea. In an effort to find natural bioactive chemical components, twelve undescribed germacrane-type sesquiterpenoids, salcavalins A-L, were isolated from the whole plant of S. cavaleriei and were identified as analogs. This is the first study to isolate highly oxygenated germacrane-type sesquiterpenoids from this plant. The structures of these undescribed compounds were elucidated by various spectroscopic methods, and their absolute configurations were confirmed by single-crystal X-ray diffraction analysis with Cu Kα radiation and electronic circular dichroism calculations. The biological activity of these undescribed compounds on the production of tumor necrosis factor-alpha in lipopolysaccharide induced NR8383 cells was evaluated, and salcavalins I and K showed anti-inflammatory activity to some extent. Salcavalins A-C, F and L were found to be neuroprotective with antiparkinsonic potential in a nematode (Caenorhabditis elegans) model. In addition, salcavalins F and I displayed marked phytotoxic activity against radish seeds at a low concentration of 50 ppm. Our findings provide scientific justification to show that bioactive sesquiterpenoids from the edible herb have anti-inflammatory in vitro, neuroprotective and phytotoxic activities.


Subject(s)
Drugs, Chinese Herbal , Salvia , Sesquiterpenes , Molecular Structure , Sesquiterpenes, Germacrane/pharmacology , Sesquiterpenes, Germacrane/chemistry , Salvia/chemistry , Drugs, Chinese Herbal/chemistry , Anti-Inflammatory Agents , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry
8.
J Ethnopharmacol ; 305: 116074, 2023 Apr 06.
Article in English | MEDLINE | ID: mdl-36577490

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge. AR was the main medicine in a Chinese traditional prescription called Fangji Huangqi Decoction, and it has been used to treating nephrotic syndrome (NS) for thousands of years in China. In recent years, AR has been evidenced to have anti-inflammatory activity, antihyperglycemic activity, antioxidant activity, etc. There are two mainstream commodities for ARs in the market including the imitation wild AR and transplanted AR. However, it is not clear whether the imitation wild AR or transplanted AR and which kind of component, astragalus saponin, astragalus flavonoid or astragalus polysaccharide, makes a bigger contribution in treating NS. And the exact molecular mechanism is not fully understood. AIM OF THE STUDY: To explore which kind of AR and which kind of component in AR makes the bigger contribution in treating NS, and exploring the molecular mechanism. MATERIALS AND METHODS: Firstly, HPLC-UV/ELSD was used for quantitative determination of the constituents in different ARs. Secondly, the efficacy of different ARs treating doxorubicin-induced nephropathy (DN) was compared by metabolomics. Thirdly, the protective effects of different constituents from ARs on the damage of MPC5 cells induced by adriamycin are validated. Finally, the effective constituents and mechanism of ARs against doxorubicin-induced nephropathy were investigated by network pharmacology and molecular docking. RESULTS: Quantitative determination experiment and pharmacological experiment indicated that the AR produced from Gansu province (China) (transplanted AR) with a higher proportion of total saponins, has better efficacy in the treatment for DN. And the cell experiment validated the result that astragalus saponins has the better efficacy in protecting the podocyte against injury than astragalus flavonoids and polysaccharides. The network pharmacology and molecular docking study indicated that astragalus saponins were the main constituent of AR in the treatment for DN. The mechanism may involve in GnRH signaling pathway, VEGF signaling pathway and metabolic pathways, especially of bilirubin metabolism. CONCLUSIONS: Transplanted AR has better efficacy in the treatment for NS than imitation wild AR, astragalus saponins have better efficacy in the treatment for NS than astragalus flavonoids and polysaccharides.


Subject(s)
Astragalus Plant , Drugs, Chinese Herbal , Kidney Diseases , Saponins , Humans , Molecular Docking Simulation , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Doxorubicin , Saponins/pharmacology , Saponins/therapeutic use , Flavonoids/pharmacology , Polysaccharides
9.
J Chromatogr Sci ; 61(9): 852-862, 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-36250324

ABSTRACT

Fangji Huangqi Decoction (FHD) is a classic prescription of traditional Chinese medicine which is recorded in "Jin Gui Yao Lue". The purpose of this study is to develop a method for simultaneous determination multicomponent in FHD. The separation of the 19 compounds that included calycosin, calycosin-7-O-ß-D-glucoside, formononetin, ononin, methylnissolin, methylnissolin-3-O-glucoside, isomucronulatol, tetrandrine, fangchinoline, atractylenolide-I, atractylenolide-III, liquiritigenin, liquiritin, isomucronulatol-7-O-ß-D-glucoside, astragaloside-I, astragaloside-II, astragaloside-III, astragaloside-IV and glycyrrhetinic acid were achieved by linear gradient elution. The 19 components were identified by comparing the chromatographic peaks with the reference compounds and were quantitatively analyzed by multiple reaction monitoring. This method was strict validated with recovery (96.10-101.70%), precision [relative standard deviation (RSD), 1.34-3.34%], stability (RSD, 1.49-3.80%) and repeatability (RSD, 1.60-3.49%), respectively. All the compounds showed good linearities (R2 > 0.999). The limit of detection (LOD) and limit of quantitation (LOQ) for the 19 compounds were in the range of 0.03-0.27 µg/mL (LODs) and 0.05-1.23 µg/mL (LOQs). The correlation analysis indicated that astragalus flavonoids were negatively correlated with astragalosides, tetrandrine and their corresponding flavonoid glycosides, and atractylenolides were positively correlated with astragalosides and fangchinoline. This method proved to be reliable and effective, which would give a helpful basis for the quality control, pharmacological and pharmacokinetic of FHD.


Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Rats , Animals , Tandem Mass Spectrometry/methods , Rats, Sprague-Dawley , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Glucosides/chemistry , Flavonoids/analysis
10.
Phytochemistry ; 205: 113501, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36343681

ABSTRACT

Salvia has been regarded as a beneficial healing herb in ancient Egypt, Rome and Greece, and is listed as an official medicine in the pharmacopoeias of many countries worldwide. Currently, Salvia is widely used to flavor and preserve food. Here, two undescribed norabietane-type diterpenoids, sadigitaloides A and B, two undescribed germacrane-type sesquiterpenoids, sadigitaloides C and D, five undescribed guaiane-type sesquiterpenoid lactones, sadigitaloides E-I, two undescribed noreudesmane-type sesquiterpenoids, sadigitaloides J and K, one known diterpenoid, three known sesquiterpenoids, and three other types of known compounds were isolated from the 95% ethanol extract of the whole plants of Salvia digitaloides. Their structures and absolute configurations were characterized using 1D and 2D NMR spectroscopic techniques, electronic circular dichroism (ECD) calculations, HRESIMS experiments, and single-crystal X-ray diffraction analysis. Some compounds were evaluated for their anti-inflammatory activities against lipopolysaccharide (LPS)-induced TNF-α production in rat macrophage NR8383 cells. Sadigitaloide A showed noticeable anti-inflammatory activity at a concentration of 100.0 µM. At a concentration of 60 µM, sadigitaloide B exhibited better protection of dopaminergic neurons than the positive control n-butylidenephthalide in the Caenorhabditis elegans model injured by 6-OHDA. The phytotoxic activities of some compounds were attributed to considerable inhibitory effects on the growth of the roots and hypocotyls of Raphanus sativus L seedlings, especially cis, trans-abscisic acid, whose inhibition rates were much higher than those of glyphosate at concentrations ranging from 50 to 400 ppm. These results indicated that abietane-type diterpenoids possessed excellent anti-inflammatory and neuroprotective activities and further suggested that the low-molecular-weight compounds exhibited outstanding phytotoxic activities.


Subject(s)
Salvia , Animals , Rats , Anti-Inflammatory Agents , Greece
11.
Nat Prod Res ; : 1-7, 2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36260069

ABSTRACT

A new clerodane diterpenoid, crotolanin A (1), along with three known clerodane diterpenoids, crotoeurin B (2), teucvidin (3) and teucvin (4), was isolated from the ethanol extract of the leaves and twigs of Croton lachnocarpus Benth. Their structures were identified by extensive NMR spectroscopic and HRESIMS analyses. The dopaminergic neuroprotective activity of compounds 1-4 was tested by using transgenic Caenorhabditis elegans pathological model. Compound 2 alleviated dopaminergic neuron degeneration of worms induced by 6-hydroxydopamine (6-OHDA) that represented a potential therapy for Parkinson's disease (PD).

12.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(5): 574-577, 2022 Sep 30.
Article in Chinese | MEDLINE | ID: mdl-36254490

ABSTRACT

This study briefly introduces the basic theory of sterilization, the characteristics of ethylene oxide sterilization for medical devices and the key factors about sterilization effectiveness, analyzes and compares three methods used in the product release of medical devices sterilized by ethylene oxide: test for sterility, traditional release and parametric release, and focuses on the theoretical basis, feasibility, validation requirements, advantages and disadvantages of parametric release.


Subject(s)
Ethylene Oxide , Sterilization , Sterilization/methods
13.
Int J Mol Sci ; 23(17)2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36077432

ABSTRACT

Alzheimer's disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aß1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aß monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.


Subject(s)
Alzheimer Disease , Caenorhabditis elegans Proteins , Neurodegenerative Diseases , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Animals, Genetically Modified , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Disease Models, Animal , Oxidative Stress , Phenanthrenes , Reactive Oxygen Species/metabolism
14.
Front Chem ; 10: 911543, 2022.
Article in English | MEDLINE | ID: mdl-35815214

ABSTRACT

One novel diterpenoid lactone named caesalpinbondin A (1) that possesses an unprecedented tetracyclic ring system in which a 6/6/5-fused tricyclic ring and a 4,5-dimethyldihydrofuran-2(3H)-one were connected by a C-C single bond comprising a 5-(naphtho [2,3-b]furan-7-yl)dihydrofuran-2(3H)-one moiety was isolated from the seeds of Caesalpinia bonduc. Its chemical structure was established by extensive spectroscopic methods, and its absolute configuration was further determined by single-crystal X-ray diffraction analysis and electronic circular dichroism calculation. The biological evaluation suggested that compound 1 demonstrated potent anti-Alzheimer's disease (AD) bioactivity, which could delay paralysis of transgenic AD Caenorhabditis elegans. A possible biogenetic pathway of 1 was also proposed.

15.
Int J Mol Sci ; 23(12)2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35743309

ABSTRACT

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aß-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Aß-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Aß monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.


Subject(s)
Alzheimer Disease , Caenorhabditis elegans Proteins , Diterpenes , Neurodegenerative Diseases , Acetylcholinesterase/metabolism , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Animals, Genetically Modified , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Disease Models, Animal , Diterpenes/pharmacology , Forkhead Transcription Factors/genetics , Paralysis/chemically induced , RNA, Messenger/metabolism
16.
Artif Intell Med ; 128: 102308, 2022 06.
Article in English | MEDLINE | ID: mdl-35534146

ABSTRACT

Left ventricular assist device (LVAD) is an effective method to treat ventricular failure. According to the physiological conditions of different patients, the device adaptively adjusts its rotation speed to change LVAD output. In this study, a physiological control system for LVAD based on deep reinforcement learning (DRL) is proposed. The system estimates the amount of blood required by LVAD based on a Starling-like method. The DRL controller regulates LVAD to adjust the speed and quickly approach the target value. The changes of vascular resistance, myocardial contractility, and the transition from rest to exercise were simulated, and the single factor and mixed factor experiments were carried out to compare the effects of DRL controller and proportional integral derivative (PID) controller, which controls the system according to the difference between measured variables and expected values. Two metrics are used to illustrate the regulation effect: the sum of absolute error (SAE) and the response time of the two controllers, where SAE is the difference between the estimated required pumped blood flow LVADQe and the actual measured blood flow LVADQm. The experimental result shows that the SAE of the DRL controller is 47.6% of that of the PID controller, and the response time of the DRL controller is 38.6% of that of the PID controller. This study demonstrates that the LVAD based on the DRL controller can respond more quickly and more effectively to the different physiological needs of a variety of patients than a PID controller.


Subject(s)
Heart Failure , Heart-Assist Devices , Algorithms , Computer Simulation , Heart Failure/therapy , Humans , Models, Cardiovascular
17.
Front Surg ; 9: 794420, 2022.
Article in English | MEDLINE | ID: mdl-35198596

ABSTRACT

PURPOSE: The best way to reduce seroma formation after laparoscopic indirect hernia repair is debated. We noticed that internal ring defect closure in laparoscopic mesh hernioplasty could provide promising outcomes with an effect on diminishing seroma formation. We introduce our closure technique and report our experience. METHODS: This prospective study was conducted from May 2019 to May 2021. Patients with European Hernia Society classification L3 indirect or scrotal hernia were recruited and underwent laparoscopic transabdominal patch plasty (TAPP). Hernia defect closure was performed before mesh deployment. The primary outcomes were seroma formation, postoperative pain, and hernia recurrence. Perioperative data and postoperative complications were also recorded. RESULTS: Consecutive 77 patients with 89 indirect hernias (including 51 scrotal hernias) were recruited in two regional tertiary hospitals. All operations were successful without open conversion. The mean size of the hernia defect was 3.7 ± 0.5 cm (range, 2.5-5.0 cm). The mean operative time for each hernia repair (peritoneum to peritoneum) was 48.3 ± 10.8 min (range, 33-72 min), and the mean time required for internal ring closure was 6.7 ± 2.2 min (range, 4-10 min). Intraoperative bleeding was minimal. The mean visual analog scale pain score at rest on the first postoperative day was 2.2 (range, 1-4). The average postoperative length of hospital stay was 18 h (range, 14-46 h). During a mean follow-up period of 9.4 months (range, 3-23 months), no hernia recurrence or chronic pain were noted. Seroma formation was detected on six sides of unilateral hernias (6.7%) on postoperative day 7, with a mean volume of 45.8 ml (range, 24-80 ml). All seromas were mild and resolved spontaneously within 3 months, with no need for evacuation or other treatment and without major impact on the final outcome. CONCLUSIONS: Defect closure in laparoscopic mesh hernioplasty for large indirect hernias is safe and feasible and can significantly reduce postoperative seroma formation and relative complications. This approach is recommended in large indirect or scrotal hernia repair.

18.
Nat Prod Res ; 36(9): 2306-2313, 2022 May.
Article in English | MEDLINE | ID: mdl-33089720

ABSTRACT

A new highly oxygenated germacranolide, carcerlane A (1), together with four known highly oxygenated germacranolides (2-5), was isolated from an ethanol extract of the whole plant of Carpesium nepalense var. lanatum (C.B.Clarke) Kitam. The structures were determined by HRESIMS and extensive analysis of their spectroscopic data including IR, 1 D and 2 D NMR spectra. To our best knowledge, it was the first time to report the phytochemical investigation on this plant. The anti-Alzheimer's disease (AD) activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. All the tested compounds showed that they have the anti-AD bioactivities of delaying worms paralysis.


Subject(s)
Antineoplastic Agents, Phytogenic , Asteraceae , Antineoplastic Agents, Phytogenic/chemistry , Asteraceae/chemistry , Molecular Structure , Sesquiterpenes, Germacrane/chemistry , Sesquiterpenes, Germacrane/pharmacology
19.
Anim Biotechnol ; 33(7): 1504-1509, 2022 Dec.
Article in English | MEDLINE | ID: mdl-33879023

ABSTRACT

Cell division cycle 25 A (CDC25A) accounts for an essential function on early folliculogenesis of female mammals, especially regulating the function of intra-ovarian, thus this gene is pinpointed as a candidate gene that influences the kidding number of goat. On this ground, the purpose of this study was to investigate whether the reported 20-nt nucleotide variants locus (rs639467625) of the CDC25A gene influences kidding number in Shaanbei white cashmere goat (SBWC). The χ2-test showed that there were more ID genotypes in mothers of multiple lambs than in mothers of single lambs. Interestingly, this indel locus was related to the first-born kidding number in the group of SBWC goats (p < 0.05). Similarly, the result of the t-test was consistent with the result of the χ2-test, showed the kidding number of ID genotype individuals was large than that of II individuals (p < 0.05). These findings proved that the different genotypes of CDC25A have impacts on goat kidding numbers. Thus, the results led us to speculate that the ID genotype of CDC25A was one of the main indel influencing goat kidding numbers. Simultaneously, this study was expected to provide useful DNA markers for superior individuals selection by marker-assisted selection (MAS) and make a contribution to goats breeding.


Subject(s)
Goats , INDEL Mutation , Pregnancy , Female , Animals , Sheep , Litter Size/genetics , Goats/genetics , Mutation , Cell Cycle
20.
Ecotoxicol Environ Saf ; 222: 112536, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34303043

ABSTRACT

As a widely existing traditional Chinese medicine component, TP (triptolide) has serious reproductive toxicity which causes severe damage to the reproductive system and limits its application prospect. TP and MET (metformin) have shown great potential in combined with each other in anticancer and anti-inflammatory. Whether metformin can resist the reproductive toxicity caused by triptolide, the effects of MET on TP-induced reproductive capacity has not been reported. In this study, metformin was used to investigate the therapeutic effect on reproductive toxicity induced by TP in rat. The results showed that metformin had significant therapeutic effects on oxidative stress damage, destruction of the blood-testosterone barrier and apoptosis. And it proved that its therapeutic effect is mainly to restore the structural and functional stability of testis through antioxidant stress. It will provide guidance for the treatment of reproductive toxicity caused by TP and the adjuvant detoxification of TP application.


Subject(s)
Diterpenes , Metformin , Phenanthrenes , Animals , Diterpenes/toxicity , Epoxy Compounds/toxicity , Male , Metformin/toxicity , Phenanthrenes/toxicity , Rats , Testis
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