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1.
BMC Cancer ; 24(1): 667, 2024 May 31.
Article En | MEDLINE | ID: mdl-38822303

BACKGROUND: The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a subject of debate. Hence, the objective of this study is to evaluate the impact of lipid-lowering medications on the occurrence risk of OC and CC through Mendelian randomization (MR) analysis of drug targets. METHODS: This investigation concentrated on the primary targets of lipid-lowering medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR and PCSK9 were derived from published genome-wide association study (GWAS) findings to serve as substitutes for HMGCR and PCSK9 inhibitors. Employing a MR approach, an analysis was conducted to scrutinize the impact of inhibitors targeting HMGCR and PCSK9 on the occurrence of OC and CC. Coronary heart disease (CHD) risk was utilized as a positive control, and the primary outcomes encompassed OC and CC. RESULTS: The findings of the study suggest a notable elevation in the risk of OC among patients treated with HMGCR inhibitors (OR [95%CI] = 1.815 [1.316, 2.315], p = 0.019). In contrast, no significant correlation was observed between PCSK9 inhibitors and the occurrence of OC. Additionally, the analysis did not reveal any noteworthy connection between HMGCR inhibitors, PCSK9 inhibitors, and CC. CONCLUSION: HMGCR inhibitors significantly elevate the risk of OC in patients, but their mechanism needs further investigation, and no influence of PCSK9 inhibitors on OC has been observed. There is no significant relationship between HMGCR inhibitors, PCSK9 inhibitors, and CC.


Genome-Wide Association Study , Hydroxymethylglutaryl CoA Reductases , Mendelian Randomization Analysis , Ovarian Neoplasms , Proprotein Convertase 9 , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/drug therapy , Hydroxymethylglutaryl CoA Reductases/genetics , Ovarian Neoplasms/genetics , Ovarian Neoplasms/drug therapy , Proprotein Convertase 9/genetics , Hypolipidemic Agents/therapeutic use , Hypolipidemic Agents/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Polymorphism, Single Nucleotide
2.
Behav Brain Res ; 465: 114968, 2024 May 08.
Article En | MEDLINE | ID: mdl-38521360

PURPOSE: Depression is a psychiatric disorder and the treatment of depression is an urgent problem that need to be solved. Gastrodin (GAS) is a Traditional Chinese Medicine from an orchid and is used for neurological diseases, including depressive disorders. METHODS: To assess the effect of GAS on gut microbiota of depressive mice, we established a chronic unpredictable mild stress (CUMS)-induced mouse model, and GAS was administered to one group of the mice. Animal behavior experiments were used to detect depressive-like behaviors, and 16 S rRNA gene analysis was applied to detect the gut microbiota of each group. All raw sequences were deposited in the NCBI Sequence Read Archive under accession number SRP491061. RESULTS: GAS treatment significantly improved depressive-like behaviors as well as the diversity and abundance of the gut microbiota. The depressive-like behaviors of the CUMS-GAS group were improved in different degrees compared with the CUMS group. The linear discriminant analysis (LDA) of the gut microbiota showed that the makeup of the gut microbiota in mice changed dramatically in the CUMS-GAS group, compared with the CUMS group, Bacteroides (LDA = 3.94, P < 0.05) were enriched in the CUMS-GAS group at the genus level. In comparison to the CUMS group, the CUMS-GAS group had a greater concentration numbers of Lactobacillus, Corynebacterium, Staphylococcus, Bacteroides, Psychrobacter, and Alistipes. CONCLUSION: Our results suggested that GAS improved depressive-like behaviors in mice and impacted the microbial composition of the gut. Our research indicated that dysbiosis of the gut microbiota may be affected by GAS treatment, which improved depressive-like behaviors in the CUMS-induced mouse model of depression.


Benzyl Alcohols , Depression , Gastrointestinal Microbiome , Glucosides , Humans , Mice , Animals , Depression/drug therapy , Depression/psychology , Behavior, Animal , Stress, Psychological/complications
3.
J Hand Ther ; 2024 Feb 12.
Article En | MEDLINE | ID: mdl-38350809

BACKGROUND: Phalangeal fractures are amongst the most challenging injuries that hand surgeons and hand therapists treat. Traditionally, these have been managed operatively, but are often fraught with potential problems including contractures, deformities and loss of motion. PURPOSE: To provide evidence supporting the use of non-invasive skin traction orthosis as an effective treatment option. STUDY DESIGN: Retrospective cohort. METHODS: We performed a retrospective review of outpatients with phalangeal fractures treated with non-invasive skin traction orthoses in our institution from January 2021 till June 2022. Demographic information, injury specifics and radiological findings were extracted from medical records. Outcome measures included total arc of motion (TAM) and dorsal angulation angles. RESULTS: Fourteen patients (17 fractures) with a mean age of 48 years (SD21.3) were included. Ten patients had single digit injuries, while four patients had two digits in traction within the same splint. 70.6% were proximal phalangeal fractures. 76.5% of the fractures were extra-articular and 58.8% non-comminuted. Median duration of orthosis use was 18 days (IQR 8-21). Patients with forearm-based orthoses had significantly longer traction time. There was a significant improvement (p = 0.001) from median baseline TAM (124°) to final TAM readings (245°). Younger patients with ulnar digit fractures or extra-articular fractures had a shorter rehabilitation period. There is no significant difference in clinical outcomes between the use of forearm-based or hand-based orthoses. CONCLUSION: We recommend the use of the hand-based non-invasive skin traction orthosis as an option in managing phalangeal fractures as it is a simple, inexpensive and non-invasive procedure with promising results. Care must be taken to ensure frequent change of traction tapes to maintain good skin integrity, and to avoid loss of tension. Radiological imaging should be performed after each traction tape change to ensure good alignment is maintained.

4.
Langmuir ; 40(4): 1988-2004, 2024 Jan 30.
Article En | MEDLINE | ID: mdl-38227964

Single-molecule electronics can fabricate single-molecule devices via the construction of molecule-electrode interfaces and also provide a unique tool to investigate single-molecule scale physicochemical processes at these interfaces. To investigate single-molecule electronic devices with desired functionalities, an understanding of the interface evolution processes in single-molecule devices is essential. In this review, we focus on the evolution of molecule-electrode interface properties, including the background of interface evolution in single-molecule electronics, the construction of different types of single-molecule interfaces, and the regulation methods. Finally, we discuss the perspective of future characterization techniques and applications for single-molecule electronic interfaces.

5.
J Adv Res ; 2023 Dec 25.
Article En | MEDLINE | ID: mdl-38151116

INTRODUCTION: Light-harvesting chlorophyll a/b-binding (LHCB) protein complexes of photosystem II are integral to the formation of thylakoid structure and the photosynthetic process. They play an important role in photoprotection, a crucial process in leaf development under low-temperature stress. Nonetheless, potential key genes directly related to low-temperature response and albino phenotype have not been precisely identified in tea plant. Moreover, there are no studies simultaneously investigating multiple albino tea cultivars with different temperature sensitivity. OBJECTIVES: The study aimed to clarify the basic characteristics of CsLHCB gene family members, and identify critical CsLHCB genes potentially influential in leaf color phenotypic variation and low-temperature stress response by contrasting green and albino tea cultivars. Concurrently, exploring the differential expression of the CsLHCB gene family across diverse temperature-sensitive albino tea cultivars. METHODS: We identified 20 putative CsLHCB genes according to phylogenetic analysis. Evolutionary relationships, gene duplication, chromosomal localization, and structures were analyzed by TBtools; the physiological and biochemical characteristics were analyzed by protein analysis websites; the differences in coding sequences and protein accumulation in green and albino tea cultivars, gene expression with maturity were tested by molecular biology technology; and protein interaction was analyzed in the STRING database. RESULTS: All genes were categorized into seven groups, mapping onto 7 chromosomes, including three tandem and one segmental duplications. They all own a conserved chlorophyll A/B binding protein domain. The expression of CsLHCB genes was tissue-specific, predominantly in leaves. CsLHCB5 may play a key role in the process of leaf maturation and senescence. In contrast to CsLHCB5, CsLHCB1.1, CsLHCB2, and CsLHCB3.2 were highly conserved in amino acid sequence between green and albino tea cultivars. In albino tea cultivars, unlike in green cultivars, the expression of CsLHCB1.1, CsLHCB1.2, and CsLHCB2 was down-regulated under low-temperature stress. The accumulation of CsLHCB1 and CsLHCB5 proteins was lower in albino tea cultivars. Greater accumulation of CsLHCB2 protein was detected in RX1 and RX2 compared to other albino cultivars. CONCLUSIONS: CsLHCB1.1, CsLHCB1.2, and CsLHCB2 played a role in the response to low-temperature stress. The amino acid sequence site mutation of CsLHCB5 would distinguish the green and albino tea cultivars. The less accumulation of CsLHCB1 and CsLHCB5 had a potential influence on albino leaves. Albino cultivars more sensitive to temperature exhibited lower CsLHCB gene expression. CsLHCB2 may serve as an indicator of temperature sensitivity differences in albino tea cultivars. This study could provide a reference for further studies of the functions of the CsLHCB family and contribute to research on the mechanism of the albino in tea plant.

6.
Ultrasound Med Biol ; 49(12): 2497-2509, 2023 12.
Article En | MEDLINE | ID: mdl-37730479

OBJECTIVE: The goal of the work described here was to develop and assess a deep learning-based model that could automatically segment anterior chamber angle (ACA) tissues; classify iris curvature (I-Curv), iris root insertion (IRI), and angle closure (AC); automatically locate scleral spur; and measure ACA parameters in ultrasound biomicroscopy (UBM) images. METHODS: A total of 11,006 UBM images were obtained from 1538 patients with primary angle-closure glaucoma who were admitted to the Eye Center of Renmin Hospital of Wuhan University (Wuhan, China) to develop an imaging database. The UNet++ network was used to segment ACA tissues automatically. In addition, two support vector machine (SVM) algorithms were developed to classify I-Curv and AC, and a logistic regression (LR) algorithm was developed to classify IRI. Meanwhile, an algorithm was developed to automatically locate the scleral spur and measure ACA parameters. An external data set of 1,658 images from Huangshi Aier Eye Hospital was used to evaluate the performance of the model under different conditions. An additional 439 images were collected to compare the performance of the model with experts. RESULTS: The model achieved accuracies of 95.2%, 88.9% and 85.6% in classification of AC, I-Curv and IRI, respectively. Compared with ophthalmologists, the model achieved an accuracy of 0.765 in classifying AC, I-Curv and IRI, indicating that its high accuracy was as high as that of the ophthalmologists (p > 0.05). The average relative errors (AREs) of ACA parameters were smaller than 15% in the internal data sets. Intraclass correlation coefficients (ICCs) of all the angle-related parameters were greater than 0.911. ICC values of all iris thickness parameters were greater than 0.884. The accurate measurement of ACA parameters partly depended on accurate localization of the scleral spur (p < 0.001). CONCLUSION: The model could effectively and accurately evaluate the ACA automatically based on fully automated analysis of UBM images, and it can potentially be a promising tool to assist ophthalmologists. The present study suggested that the deep learning model can be extensively applied to the evaluation of ACA and AC-related biometric risk factors, and it may broaden the application of UBM imaging in the clinical research of primary angle-closure glaucoma.


Deep Learning , Glaucoma, Angle-Closure , Humans , Glaucoma, Angle-Closure/diagnostic imaging , Microscopy, Acoustic/methods , Gonioscopy , Tomography, Optical Coherence/methods , Anterior Chamber
7.
Chem Sci ; 14(22): 6079-6086, 2023 Jun 07.
Article En | MEDLINE | ID: mdl-37293661

The nitrogen doping of graphene leads to graphene heterojunctions with a tunable bandgap, suitable for electronic, electrochemical, and sensing applications. However, the microscopic nature and charge transport properties of atomic-level nitrogen-doped graphene are still unknown, mainly due to the multiple doping sites with topological diversities. In this work, we fabricated atomically well-defined N-doped graphene heterojunctions and investigated the cross-plane transport through these heterojunctions to reveal the effects of doping on their electronic properties. We found that a different doping number of nitrogen atoms leads to a conductance difference of up to ∼288%, and the conductance of graphene heterojunctions with nitrogen-doping at different positions in the conjugated framework can also lead to a conductance difference of ∼170%. Combined ultraviolet photoelectron spectroscopy measurements and theoretical calculations reveal that the insertion of nitrogen atoms into the conjugation framework significantly stabilizes the frontier molecular orbitals, leading to a change in the relative positions of the HOMO and LUMO to the Fermi level of the electrodes. Our work provides a unique insight into the role of nitrogen doping in the charge transport through graphene heterojunctions and materials at the single atomic level.

8.
Front Med (Lausanne) ; 10: 1164188, 2023.
Article En | MEDLINE | ID: mdl-37153082

Objective: In order to automatically and rapidly recognize the layers of corneal images using in vivo confocal microscopy (IVCM) and classify them into normal and abnormal images, a computer-aided diagnostic model was developed and tested based on deep learning to reduce physicians' workload. Methods: A total of 19,612 corneal images were retrospectively collected from 423 patients who underwent IVCM between January 2021 and August 2022 from Renmin Hospital of Wuhan University (Wuhan, China) and Zhongnan Hospital of Wuhan University (Wuhan, China). Images were then reviewed and categorized by three corneal specialists before training and testing the models, including the layer recognition model (epithelium, bowman's membrane, stroma, and endothelium) and diagnostic model, to identify the layers of corneal images and distinguish normal images from abnormal images. Totally, 580 database-independent IVCM images were used in a human-machine competition to assess the speed and accuracy of image recognition by 4 ophthalmologists and artificial intelligence (AI). To evaluate the efficacy of the model, 8 trainees were employed to recognize these 580 images both with and without model assistance, and the results of the two evaluations were analyzed to explore the effects of model assistance. Results: The accuracy of the model reached 0.914, 0.957, 0.967, and 0.950 for the recognition of 4 layers of epithelium, bowman's membrane, stroma, and endothelium in the internal test dataset, respectively, and it was 0.961, 0.932, 0.945, and 0.959 for the recognition of normal/abnormal images at each layer, respectively. In the external test dataset, the accuracy of the recognition of corneal layers was 0.960, 0.965, 0.966, and 0.964, respectively, and the accuracy of normal/abnormal image recognition was 0.983, 0.972, 0.940, and 0.982, respectively. In the human-machine competition, the model achieved an accuracy of 0.929, which was similar to that of specialists and higher than that of senior physicians, and the recognition speed was 237 times faster than that of specialists. With model assistance, the accuracy of trainees increased from 0.712 to 0.886. Conclusion: A computer-aided diagnostic model was developed for IVCM images based on deep learning, which rapidly recognized the layers of corneal images and classified them as normal and abnormal. This model can increase the efficacy of clinical diagnosis and assist physicians in training and learning for clinical purposes.

9.
Org Lett ; 25(10): 1683-1688, 2023 Mar 17.
Article En | MEDLINE | ID: mdl-36883803

A visible-light-induced hydrocyclization of unactivated alkenes was developed using 3CzClIPN as the photocatalyst to generate substituted α-methyldeoxyvasicinones and α-methylmackinazolinones in moderate to good yields. An intermolecular hydrogen atom transfer with THF as the hydrogen source was involved. Mechanism studies indicated that the intramolecular addition of the in situ formed aminal radical to the unactivated alkene generated the polycyclic quinazolinone.

10.
Sci Adv ; 9(6): eadf0425, 2023 Feb 10.
Article En | MEDLINE | ID: mdl-36753541

Single-molecule electronics offer a unique strategy for the miniaturization of electronic devices. However, the existing experiments are limited to the conventional molecular junctions, where a molecule anchors to the electrode pair with linkers. With such a rod-like configuration, the minimum size of the device is defined by the length of the molecule. Here, by incorporating a single molecule with two single-layer graphene electrodes, we fabricated layer-by-layer single-molecule heterojunctions called single-molecule two-dimensional van der Waals heterojunctions (M-2D-vdWHs), of which the sizes are defined by the thickness of the molecule. We controlled the conformation of the M-2D-vdWHs and the cross-plane charge transport through them with the applied electric field and established that they can serve as reversible switches. Our results demonstrate that the M-2D-vdWHs, as stacked from single-layer 2D materials and a single molecule, can respond to electric field stimulus, which promises a diverse class of single-molecule devices with unprecedented size.

11.
Org Lett ; 25(3): 494-499, 2023 Jan 27.
Article En | MEDLINE | ID: mdl-36634986

The annulation reactions of N-allylbenzamides with N-sulfonylaminopyridinium salts were developed under metal-free photoinduced mild conditions. Substituent-controlled sulfonaminoarylation and sulfonaminooxylation of benzamides were realized: N-allylbenzamides lead to benzosultams, while N-(2-phenylallyl)benzamides give sulfonamidylated oxazoline derivatives. Control experiments indicated that those reactions undergo a radical pathway with arylsulfonamidyl radicals as the intermediates. The aryl C-H bond functionalization in arylsulfonamidyl was involved for the first time to give benzosultams.

13.
PLoS One ; 17(12): e0278907, 2022.
Article En | MEDLINE | ID: mdl-36520790

OBJECTIVE: This study offers meta-analytic data on the potential association between epilepsy and depression especially for the prevalence of depression in epilepsy or vice versa. METHODS: The relevant studies were searched and identified from nine electronic databases. Studies that mentioned the prevalence and/or incidence of epilepsy and depression were included. Hand searches were also included. The search language was English and the search time was through May 2022. Where feasible, random-effects models were used to generate pooled estimates. RESULTS: After screening electronic databases and other resources, 48 studies from 6,234 citations were included in this meta-analysis. The period prevalence of epilepsy ranged from 1% to 6% in patients with depression. In population-based settings, the pooled period prevalence of depression in patients with epilepsy was 27% (95% CI, 23-31) and 34% in clinical settings (95% CI, 30-39). Twenty studies reported that seizure frequency, low income, unemployment of the patients, perception of stigma, anxiety, being female, unmarried status, disease course, worse quality of life, higher disability scores, and focal-impaired awareness seizures were risk factors for depression. CONCLUSION: Our study found that epilepsy was associated with an increased risk of depression. Depression was associated with the severity of epilepsy.


Epilepsies, Partial , Epilepsy , Humans , Female , Male , Depression/complications , Depression/epidemiology , Quality of Life , Epilepsy/complications , Epilepsy/epidemiology , Seizures/complications
14.
Biochem Biophys Res Commun ; 635: 187-193, 2022 12 20.
Article En | MEDLINE | ID: mdl-36279680

BACKGROUND: Decellularized adipose tissue (DAT) provides a suitable microenvironment for adipose stem cells (ADSCs) and promotes their adipogenic differentiation. Recent studies have focused on allogeneic DAT; however, insufficient adipose sources limit its wider application of allogeneic DAT. In this study, we compared the ability of allogeneic and xenogeneic DATs to induce adipose regeneration to explore the feasibility of xenogeneic DAT as an adjunctive material for tissue repair. METHODS: Decellularized adipose tissue from humans and rabbits was prepared using the Flynn's method. The proliferation, migration, and adipogenic functions of the allogeneic and the xenogeneic groups were compared. Rabbits were used to construct transplantation models: allogeneic (transplanted r-DAT) and xenogeneic groups (transplanted h-DAT). Comparison of DAT transplantation outcomes between the two groups. RESULTS: Xenogeneic DAT supports adipose regeneration. In vitro, adipose-derived stem cells cultured on xenogeneic DAT developed adipogenesis without media cues and were not statistically different from the effects of allogeneic DAT on cell migration, proliferation, and adipogenic capacity. In vivo, the animal model showed angiogenesis and adipogenesis, and the adipogenic ability of xenogeneic DAT was not statistically different from that of allogeneic DAT. CONCLUSION: Xenogeneic DATs can induce adipose regeneration, and its adipogenic ability has no statistical difference, compared with allogeneic DATs. Xenografts are expected to be useful for soft tissue repair.


Adipose Tissue , Tissue Scaffolds , Humans , Animals , Rabbits , Heterografts , Adipocytes , Adipogenesis , Cell Differentiation , Tissue Engineering/methods , Cells, Cultured
15.
Org Biomol Chem ; 20(39): 7746-7764, 2022 10 12.
Article En | MEDLINE | ID: mdl-36178474

2H-Indazoles are one class of the most important nitrogen-containing heterocyclic compounds. The 2H-indazole motif is widely present in bioactive natural products and drug molecules that exhibit distinctive bioactivities. Therefore, much attention has been paid to access diverse 2H-indazole derivatives. Among them, the late-stage functionalization of 2H-indazoles via C-H activation is recognized as an efficient approach for increasing the complexity and diversity of 2H-indazole derivatives. In this review, we summarized recent achievements in the late-stage functionalization of 2H-indazoles, including the C3-functionalization of 2H-indazoles through transition metal-catalyzed C-H activation or a radical pathway, transition metal-catalyzed ortho C2'-H functionalization of 2H-indazoles and remote C-H functionalization at the benzene ring in 2H-indazoles.


Biological Products , Heterocyclic Compounds , Benzene , Indazoles/pharmacology , Nitrogen
16.
Org Biomol Chem ; 20(26): 5259-5263, 2022 07 06.
Article En | MEDLINE | ID: mdl-35735246

A metal-free polychloromethyl radical-initiated cyclization of unactivated alkenes was developed using CH2Cl2 and CHCl3 as the di- and trichloromethyl radical sources. Variously substituted N-allyl-indoles were successfully transformed into the corresponding C2-(di- and trichloromethyl) pyrrolo[1,2-a]indoles in moderate to good yields. This reaction has a broad substrate scope and good functional group tolerance. Dibromomethylated products can also be obtained using CH2Br2 under standard conditions.


Alkenes , Indoles , Cyclization , Free Radicals , Metals
17.
Org Biomol Chem ; 20(15): 3067-3071, 2022 04 13.
Article En | MEDLINE | ID: mdl-35348170

An efficient arylsulfonylation/cyclization of 2-aryl-N-methacryloyl indoles with potassium metabisulfite and aryldiazonium tetrafluoroborates was developed. A series of variously substituted arylsulfonyl indolo[2,1-a]isoquinolin-6(5H)-ones were formed in moderate to good yields via utilization of the nature abundant inorganic salt potassium metabisulfite as a SO2 surrogate. Additionally, this three-component protocol can also be employed for the synthesis of arylsulfonyl-substituted benzimidazo-[2,1-a]isoquinolin-6(5H)-ones.


Indoles , Cyclization
18.
Appl Ergon ; 100: 103669, 2022 Apr.
Article En | MEDLINE | ID: mdl-34954538

PURPOSE: To assess musculoskeletal risk factors (repetitions, posture, forces) of the upper limb during domestic floor mopping tasks. METHODS: Two hundred women were surveyed to determine the most common mopping system, mopping patterns and type of flooring used in their homes. The biomechanical demands of the three most common mopping systems were then evaluated in the laboratory. Participants were also asked to rate their perceived levels of exertion and cleanliness of each mopping system. RESULTS: The use of wet wipes had the highest repetition count and exertion rates during mopping and scrubbing tasks. Higher peak scrubbing forces were noted for the plunge mop. All participants found the cotton fibre mop to be the cleanest. All 3 mops had medium postural risk. CONCLUSION: The advantages and disadvantages of each mopping system were outlined and may be used by occupational therapists when providing ergonomic advice to patients with upper limb musculoskeletal conditions.


Ergonomics , Floors and Floorcoverings , Female , Humans , Posture , Upper Extremity
19.
Front Pharmacol ; 13: 1092583, 2022.
Article En | MEDLINE | ID: mdl-36686697

Ethnopharmacological relevance: Crebanine (Cre) and Stephanine (Step) are isoquinoline aporphine-type alkaloids that are extracted from Stephania yunnanenses H. S. Lo. Plants of the Stephania genus are often used for treatment of stomach pain, abdominal pain, and rheumatoid arthritis. Both Cre and Step exhibit strong activities but are also associated with a certain level of toxicity, 10,11-dibrominecrebanine (2Br-Cre) is a bromine-modified derivative of Cre that we prepared and tested in order to reduce toxicity and enhance efficacy. Aim of this study: To investigate the anti-inflammatory and analgesic effects of 2Br-Cre and Step based on previous research findings and explore the specific biological mechanisms involved. Materials and methods: The anti-inflammatory and analgesic effects of 2Br-Cre and Step were investigated using a range of experimental models, including xylene-induced ear edema, carrageenan-induced pleurisy, carrageenan-induced paw edema, the hot-plate test, the naloxone antagonism test and the acetic acid writhing test. A model of chronic constriction injury (CCI) of the sciatic nerve was also established to investigate therapeutic effects. A RAW264.7 cell model was established using lipopolysaccharide (LPS) to estimate the effects of these compounds on cytokines levels. Results: 2Br-Cre and step significantly inhibited ear edema, paw edema and presented anti-inflammatory activity in the pleurisy model by inhibiting leukocyte migration and nitric oxide (NO) production, and by reducing the levels of PGE2. 2Br-Cre and Step significantly increased the pain threshold of mice subjected to heat stimulation; the effect was blocked by naloxone, thus suggesting that the analgesic effects of 2Br-Cre and Step were mediated by opioid receptors. 2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the levels of BDNF in the serum and brain, thus alleviating the pain caused by CCI. In addition, 2Br-Cre and Step significantly inhibited the production of several inflammatory cytokines (IL-6, IL-1ß and TNF-α) by LPS-induced RAW264.7 macrophages (p < .01). Conclusion: 2Br-Cre and Step exerted remarkable anti-inflammatory and analgesic effects. As a structural modification of Cre, 2Br-Cre retains the anti-inflammatory and analgesic activity of Cre but with better efficacy. Consequently, 2Br-Cre should be investigated further as a lead compound for analgesia.

20.
BMC Complement Med Ther ; 21(1): 284, 2021 Nov 20.
Article En | MEDLINE | ID: mdl-34801005

BACKGROUND: Stephania yunnanensis H. S. Lo is widely used as an antipyretic, analgesic and anti-inflammatory herbal medicine in SouthWest China. In this study, we investigated the anti-inflammatory activity and mechanism of sinoacutine (sino), one of the primary components extracted from this plant. METHODS: A RAW264.7 cell model was established using lipopolysaccharide (LPS) induced for estimation of cytokines in vitro, qPCR was used to estimate gene expression, western blot analysis was used to estimate protein level and investigate the regulation of NF- κB, JNK and MAPK signal pathway. In addition, an acute lung injury model was established to determine lung index and levels of influencing factors. RESULTS: Using the RAW264.7 model, we found that sino reduced levels of nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß and prostaglandin E2 (PGE2) but increased levels of IL-6. qPCR analysis revealed that sino (50, 25 µg/ml) inhibited gene expression of nitric oxide synthase (iNOS). western blot analysis showed that sino significantly inhibited protein levels of both iNOS and COX-2. Further signalling pathway analysis validated that sino also inhibited phosphorylation of p65 in the NF-κB and c-Jun NH2 terminal kinase (JNK) signalling pathways but promoted the phosphorylation of extracellular signal regulated kinase (ERK) and p38 in the MAPK signalling pathway. In addition, in a mouse model induced by LPS, we determined that sino reduced the lung index and the levels of myeloperoxidase (MPO), NO, IL-6 and TNF-α in lung tissues and bronchoalveolar lavage fluid (BALF) in acute lung injury (ALI). CONCLUSION: Taken together, our results demonstrate that sino is a promising drug to alleviate LPS-induced inflammatory reactions.


Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/pharmacology , MAP Kinase Kinase 4/metabolism , Morphinans/pharmacology , NF-kappa B/metabolism , Plant Extracts/pharmacology , Animals , Animals, Outbred Strains , Anti-Inflammatory Agents/chemistry , China , MAP Kinase Signaling System/drug effects , Male , Mice , Molecular Structure , Morphinans/chemistry , Plant Extracts/chemistry , RAW 264.7 Cells
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