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1.
Adv Mater ; : e2406636, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39148152

ABSTRACT

Bionic electrical stimulation (Bio-ES) aims to achieve personalized therapy and proprioceptive adaptation by mimicking natural neural signatures of the body, while current Bio-ES devices are reliant on complex sensing and computational simulation systems, thus often limited by the low-fidelity of simulated electrical signals, and failure of interface information interaction due to the mechanical mismatch between soft tissues and rigid electrodes. Here, the study presents a flexible and ultrathin self-sustainable bioelectronic patch (Bio-patch), which can self-adhere to the lesion area of organs and generate bionic electrical signals synchronized vagal nerve envelope in situ to implement Bio-ES. It allows adaptive adjustment of intensity, frequency, and waveform of the Bio-ES to fully meet personalized needs of tissue regeneration based on real-time feedback from the vagal neural controlled organs. With this foundation, the Bio-patch can effectively intervene with excessive fibrosis and microvascular stasis during the natural healing process by regulating the polarization time of macrophages, promoting the reconstruction of the tissue-engineered structure, and accelerating the repair of damaged liver and kidney. This work develops a practical approach to realize biomimetic electronic modulation of the growth and development of soft organs only using a multifunctional Bio-patch, which establishes a new paradigm for precise bioelectronic medicine.

2.
bioRxiv ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39149361

ABSTRACT

Phosphatidylserine externalization on the surface of dying cells is a key signal for their recognition and clearance by macrophages and is mediated by members of the X-Kell related (Xkr) protein family. Defective Xkr-mediated scrambling impairs clearance, leading to inflammation. It was proposed that activation of the Xkr4 apoptotic scramblase requires caspase cleavage, followed by dimerization and ligand binding. Here, using a combination of biochemical approaches we show that purified monomeric, full-length human Xkr4 (hXkr4) scrambles lipids. CryoEM imaging shows that hXkr4 adopts a novel conformation, where three conserved acidic residues create an electronegative surface embedded in the membrane. Molecular dynamics simulations show this conformation induces membrane thinning, which could promote scrambling. Thinning is ablated or reduced in conditions where scrambling is abolished or reduced. Our work provides insights into the molecular mechanisms of hXkr4 scrambling and suggests the ability to thin membranes might be a general property of active scramblases.

3.
Int J Biol Macromol ; 276(Pt 1): 133748, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986996

ABSTRACT

Poly-L-lactic acid (PLLA), recognized as a piezoelectric material, not only demonstrates exceptional piezoelectric properties but also exhibits commendable biocompatibility and biodegradability. These properties render PLLA highly promising for diverse applications, including sensors, wearable devices, biomedical engineering, and related domains. This review offers a comprehensive overview of the distinctive piezoelectric effect of PLLA-based material and delves into the latest advancements in its preparation strategies as a piezoelectric material. It further presents recent research progress in PLLA-based piezoelectric materials, particularly in the realms of health monitoring, skin repair, nerve regeneration, and tissue repair. The discourse extends to providing insights into potential future trajectories for the development of PLLA-based piezoelectric materials.

4.
Cell Calcium ; 121: 102896, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38749289

ABSTRACT

Phospholipid scramblases mediate the rapid movement of lipids between membrane leaflets, a key step in establishing and maintaining membrane homeostasis of the membranes of all eukaryotic cells and their organelles. Thus, impairment of lipid scrambling can lead to a variety of pathologies. How scramblases catalyzed the transbilayer movement of lipids remains poorly understood. Despite the availability of direct structural information on three unrelated families of scramblases, the TMEM16s, the Xkrs, and ATG-9, a unifying mechanism has failed to emerge thus far. Among these, the most extensively studied and best understood are the Ca2+ activated TMEM16s, which comprise ion channels and/or scramblases. Early work supported the view that these proteins provided a hydrophilic, membrane-exposed groove through which the lipid headgroups could permeate. However, structural, and functional experiments have since challenged this mechanism, leading to the proposal that the TMEM16s distort and thin the membrane near the groove to facilitate lipid scrambling. Here, we review our understanding of the structural and mechanistic underpinnings of lipid scrambling by the TMEM16s and discuss how the different proposals account for the various experimental observations.


Subject(s)
Anoctamins , Phospholipid Transfer Proteins , Humans , Anoctamins/metabolism , Anoctamins/chemistry , Animals , Phospholipid Transfer Proteins/metabolism , Phospholipid Transfer Proteins/chemistry
5.
J AAPOS ; 28(3): 103913, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38570064

ABSTRACT

The modified Nishida muscle transposition procedure, in which one-third of each vertical rectus muscle belly is sutured onto the sclera in the infero- and superotemporal quadrants without either tenotomy of the vertical rectus muscles or splitting of the vertical rectus muscle is an effective treatment for abducens nerve palsy. We report a case of inferior rectus muscle aplasia treated using the modified Nishida procedure to transpose both horizontal rectus muscles inferiorly combined with superior rectus tenotomy.


Subject(s)
Oculomotor Muscles , Ophthalmologic Surgical Procedures , Tenotomy , Humans , Oculomotor Muscles/surgery , Tenotomy/methods , Ophthalmologic Surgical Procedures/methods , Male , Abducens Nerve Diseases/surgery , Vision, Binocular/physiology , Suture Techniques , Female , Eye Movements/physiology
6.
Nat Struct Mol Biol ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684930

ABSTRACT

Activation of Ca2+-dependent TMEM16 scramblases induces phosphatidylserine externalization, a key step in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove and that Ca2+ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements underlying groove opening and how lipids reorganize outside the closed groove remain unknown. Here we directly visualize how lipids associate at the closed groove of Ca2+-bound fungal nhTMEM16 in nanodiscs using cryo-EM. Functional experiments pinpoint lipid-protein interaction sites critical for closed groove scrambling. Structural and functional analyses suggest groove opening entails the sequential appearance of two π-helical turns in the groove-lining TM6 helix and identify critical rearrangements. Finally, we show that the choice of scaffold protein and lipids affects the conformations of nhTMEM16 and their distribution, highlighting a key role of these factors in cryo-EM structure determination.

7.
Front Pediatr ; 12: 1296517, 2024.
Article in English | MEDLINE | ID: mdl-38523836

ABSTRACT

Introduction: Recent evidence suggests that blue-light phototherapy impacts gut microbiota composition in jaundiced newborns, leading to disturbances closely related to the therapy's side effects. As a result, gut microbiota may serve as a potential intervention target to mitigate these side effects. In this study, we aim to examine the effects of AB-GG (Lactobacillus rhamnosus LGG), Bb-12 (Bifidobacterium animalis Bb-12) and M-16V (Bifidobacterium breve M-16V) and their combination on the intestinal microbiota, metabolomics and phototherapy-related side effects in neonates with jaundice. Methods and analysis: A total of 100 jaundiced newborns aged two weeks or younger will be included in this randomized, single-blind (the parents knew, but the neonatologists did not know), single-center controlled trial to receive either 109 colony-forming units of AB-GG, Bb-12, M-16V, a combination of the three probiotics with blue-light phototherapy, or blue-light phototherapy alone. The experimental group will be treated with oral probiotics once daily for 30 days, while the control group will receive only blue-light phototherapy. The follow-up duration will last 30 days. The primary outcomes include changes in gut microbiota, metabolomics, and the incidence of phototherapy side effects, assessed after each phototherapy session, as well as on days 10, 20, and 30. Ethics and dissemination: The study protocol has been approved by the Ethics Committee of our institution. The findings of this trial will be submitted to a peer-reviewed pediatric journal. Its abstracts will be submitted to relevant national and international conferences. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifer (ChiCTR2000036013).

8.
Chem Commun (Camb) ; 60(26): 3484-3506, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38469709

ABSTRACT

Organosilane compounds are widely used in both organic synthesis and materials science. Particularly, 1,2-disilylated and gem-disilylated alkenes, characterized by a carbon-carbon double bond and multiple silyl groups, exhibit significant potential for subsequently diverse transformations. The versatility of these compounds renders them highly promising for applications in materials, enabling them to be valuable and versatile building blocks in organic synthesis. This review provides a comprehensive summary of methods for the preparation of cis/trans-1,2-disilylated and gem-disilylated alkenes. Despite notable advancements in this field, certain limitations persist, including challenges related to regioselectivity in the incorporation and chemoselectivity in the transformation of two nearly identical silyl groups. The primary objective of this review is to outline synthetic methodologies for the generation of these alkenes through disilylation reactions, employing silicon reagents, specifically disilanes, hydrosilanes, and silylborane reagents. The review places particular emphasis on investigating the practical applications of the C-Si bond of disilylalkenes and delves into an in-depth discussion of reaction mechanisms, particularly those reactions involving the activation of Si-Si, Si-H, and Si-B bonds, as well as the C-Si bond formation.

9.
Small ; 20(30): e2308715, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38412419

ABSTRACT

Biomolecular piezoelectric materials show great potential in the field of wearable and implantable biomedical devices. Here, a self-assemble approach is developed to fabricating flexible ß-glycine piezoelectric nanofibers with interfacial polarization locked aligned crystal domains induced by Nb2CTx nanosheets. Acted as an effective nucleating agent, Nb2CTx nanosheets can induce glycine to crystallize from edges toward flat surfaces on its 2D crystal plane and form a distinctive eutectic structure within the nanoconfined space. The interfacial polarization locking formed between O atom on glycine and Nb atom on Nb2CTx is essential to align the ß-glycine crystal domains with (001) crystal plane intensity extremely improved. This ß-phase glycine/Nb2CTx nanofibers (Gly-Nb2C-NFs) exhibit fabulous mechanical flexibility with Young's modulus of 10 MPa, and an enhanced piezoelectric coefficient of 5.0 pC N-1 or piezoelectric voltage coefficient of 129 × 10-3Vm N-1. The interface polarization locking greatly improves the thermostability of ß-glycine before melting (≈210°C). A piezoelectric sensor based on this Gly-Nb2C-NFs is used for micro-vibration sensing in vivo in mice and exhibits excellent sensing ability. This strategy provides an effective approach for the regular crystallization modulation for glycine crystals, opening a new avenue toward the design of piezoelectric biomolecular materials induced by 2D materials.

10.
STAR Protoc ; 5(1): 102846, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38265939

ABSTRACT

Organochlorides are a crucial class of electrophiles in organic synthesis. Here, we present a protocol for the cross-electrophile coupling of aryl chlorides with unactivated alkyl chlorides, facilitated by an iron/B2pin2 catalytic system. We describe steps for the coupling of aryl chlorides with alkyl chlorides, followed by purification of products. This protocol can produce alkylated products with up to 81% yield. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.


Subject(s)
Chlorides , Iron , Nickel , Molecular Structure , Catalysis
11.
bioRxiv ; 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-37609346

ABSTRACT

Activation of Ca2+-dependent TMEM16 scramblases induces the externalization of phosphatidylserine, a key molecule in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove, and that Ca2+ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements involved in groove opening and of how lipids reorganize outside the closed groove remain unknown. Using cryogenic electron microscopy, we directly visualize how lipids associate at the closed groove of Ca2+-bound nhTMEM16 in nanodiscs. Functional experiments pinpoint the lipid-protein interaction sites critical for closed groove scrambling. Structural and functional analyses suggest groove opening entails the sequential appearance of two π-helical turns in the groove-lining TM6 helix and identify critical rearrangements. Finally, we show that the choice of scaffold protein and lipids affects the conformations of nhTMEM16 and their distribution, highlighting a key role of these factors in cryoEM structure determination.

12.
Chinese Journal of Analytical Chemistry ; (12): 178-186,中插1-中插3, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1017642

ABSTRACT

The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.

13.
Psychiatry Investigation ; : 772-781, 2024.
Article in English | WPRIM (Western Pacific) | ID: wpr-1045170

ABSTRACT

Objective@#Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient’s resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects @*Methods@#This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. @*Results@#In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). @*Conclusion@#msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014564

ABSTRACT

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1028777

ABSTRACT

AIM To study the chemical constituents from the twigs of Aglaia perviridis Hiern and their total antioxidant and neuroprotective activities.METHODS The 95%ethanol extract from the twigs of A.perviridis were isolated and purified by silica gel,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant and neuroprotective activities were evaluated by T-AOC kit and MTT assay,respectively.RESULTS Twenty-one compounds were isolated and identified as 3-epicotillol(1),syringic acid(2),palmitic acid(3),di-N-pentyl phthalate(4),ethyl-4-hydroxyphenylacetate(5),7-hydroxy-6-methoxycoumarin(6),1-octanol(7),p-hydroxyphenylacetic acid(8),(+)-syringaresinol-4-O-β-D-glucopyranoside(9),(+)-episyring-4-O-β-D-glucopyranoside(10),methy-4-hydroxyphenylacetate(11),koaburaside(12),byzantionoside B(13),quercetin 3-O-α-L-rhamnopyranoside(14),(2R,3R)-(+)-glucodistylin(15),(2S,3S)-(-)-glucodistylin(16),(+)-lyoniresinol-3α-O-β-D-glucopyranoside(17),(+)-isolariciresinol-9'-O-β-D-glucopyranosidede(18),(-)-lyoniresinol-3α-O-β-D-glucopyranoside(19),phlorizin(20),β-sitosterol(21).The total antioxidant capacity of compounds2,9-10,14-20 was 10.300-38.367 U/(mmol·L-1).The neuroprotective effects of compounds 2,10 and 17 were concentration-dependent,and the optimal concentrations of compounds 9 and 15 were 50,100 μmol/L,respectively.CONCLUSION Compounds 1-20 are isolated from this plant for the first time.Compounds 2,9-10,14-20 have strong total antioxidant activities.Compounds 2,9-10,15,17 have neuroprotective activities.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1019576

ABSTRACT

Objective To explore the relationship between the types of bicuspid aortic valves(BAV)and the outcome of functional mitral regurgitation(FMR)and the affecting factors of FMR.Methods From Jun 2018 to Sep 2022,patients with severe BAV aortic valve stenosis(AS)complicated with FMR underwent post transcatheter aortic valve replacement(TAVR)in Zhongshan Hospital,Fudan University were retrospectively analyzed.The baseline information and imaging data of different BAV patients were collected.Logistic regression was used to analyze the factors affecting the outcome of FMR(improvement and non-improvement).Result A total of 100 patients with TAVR were included,including 49 patients with type 0 of BAV and 51 patients with type 1 of BAV.Compared with patients of type 1,patients of type 0 had younger age[(72.78±6.09)y vs.(77.00±8.35)y,P=0.050],lower male ratio(47%vs.73%,P= 0.009)higher BMI[(23.19±2.62)kg/m2 vs.(21.99±3.13)kg/m2,P=0.041],and lower incidence of aortic regurgitation(69%vs.92%,P=0.040).Compared with the non-improvement group,the improvement group had a lower incidence of coronary heart disease(5%vs.18%,P=0.042),higher incidence of pulmonary hypertension(20%vs.2%,P=0.007),larger left ventricular diastolic diameter[(51.98±6.74)mm vs.(48.04±7.72)mm,P=0.009]and higher maximum flow velocity[(4.86±0.95)cm/s vs.(4.47±0.75)cm/s,P= 0.023]of the aortic valve.The results of Logistic regression analysis showed that preoperative pulmonary hypertension,left ventricular end-diastolic diameter and maximum valvular flow velocity of BAV patients were the potential affecting factors of FMR improvement after TAVR.Conclusion No significant difference was found in FMR improvement between BAV patients of type 0 and type 1 after TAVR.For BAV patients with AS,preoperative pulmonary hypertension,larger left ventricular end-diastolic diameter,and faster aortic valve flow velocity were associated with higher FMR improvement rate.

17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1019610

ABSTRACT

Tricuspid regurgitation(TR)cases are widely distributed in China.Poor clinical drug efficacy,high surgical risk,and poor prognosis for right heart failure are found in patients with moderate or severe TR.In recent years,with the innovation of valve instruments and the development of technology,transcatheter tricuspid valve treatment could be a new choice for high-risk TR patients in surgery.Many TR animal models have emerged these years for the research of the mechanism of TR and for the clinical verification of instruments.Therefore,this review focuses on how to develop an animal model of TR and discusses the advantages and disadvantages of these techniques.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1020752

ABSTRACT

Objective To analyze the frailty of patients with long-term maintenance dialysis(MD)and its influencing factors,and to explore the correlation of different dialysis modalities with the re-infection of novel coronavirus infection(COVID-19)and frailty syndrome.Methods Patients with regular dialysis in Nephrology Department of the Second Affiliated Hospital of Kunming Medical University from February to June 2023 were selected.A cross-sectional survey was conducted to collect clinical data of the patients,including dialysis modality(i.e.maintenance hemodialysis,abbreviated as hemodialysis,and continuous ambulatory peritoneal dialysis,abbreviated as peritoneal dialysis),and whether with re-infection of COVID-19.Patients were divided into 3 groups using Fried's frailty phenotype(FP):non-frailty group,pre-or-intermediate frailty group,and frailty syndrome group.The clinical characteristics of the FP were compared among the three groups.The correlation of frailty with clinical data,dialysis modality,re-infection of COVID-19 in each group was compared.Multifactorial logistic regression was used to analyze the factors influencing the development of frailty syndrome in patients.Results A total of 246 dialysis patients were included in this study,with 77(31.3%)in the non-frailty group,83(33.7%)in the pre-frailty group and 86(35.0%)in the frailty syndrome group.The frailty syndrome group showed characteristics of advanced age,high pre-dialysis creatinine level,low serum albumin level and combined pleural effusion(all P<0.05).There was no statistically significant difference in the comparison of frailty between the hemodialysis and peritoneal dialysis group(P = 0.960).COVID-19 re-positive patients had higher frailty score than non-re-positive patients.Multifactor logistic regression showed that age,COVID-19 re-infection of COVID-19,serum albumin,pre-dialysis creatinine,and pleural effusion were factors influencing the development of frailty syndrome in dialysis patients(P<0.05).Conclusion There is high incidence of frailty syndrome in dialysis patients,and there is no correlation of frailty with dialysis modality.High serum albumin level is a protective factor for the development of frailty syndrome in patients,whereas re-infection of COVID-19,advanced age,high pre-dialysis blood creatinine level and pleural effusion are risk factors for the development of frailty syndrome.

19.
Article in English | WPRIM (Western Pacific) | ID: wpr-1030976

ABSTRACT

@#Objective: To determine the inhibitory effects of pachymic acid on lung adenocarcinoma (LUAD) cells and elucidate its underlying mechanism. Methods: CCK-8, wound healing, Transwell, Western blot, tube formation, and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation, metastasis, angiogenesis as well as autophagy. Subsequently, molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B (PTP1B). Moreover, PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid. Results: Pachymic acid suppressed LUAD cell viability, metastasis as well as angiogenesis while inducing cell autophagy. It also targeted PTP1B and lowered PTP1B expression. However, PTP1B overexpression reversed the effects of pachymic acid on metastasis, angiogenesis, and autophagy as well as the expression of Wnt3a and β-catenin in LUAD cells. Conclusions: Pachymic acid inhibits metastasis and angiogenesis, and promotes autophagy in LUAD cells by modulating the Wnt/ β-catenin signaling pathway via targeting PTP1B.

20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1031593

ABSTRACT

【Objective】 To describe the distribution characteristics of knee and ankle joint range of motion and muscle atrophy related indexes in patients with Kashin-Beck disease (KBD) in Shaanxi Province so as to explore the correlation of knee and ankle joint range of motion (ROM) with muscle atrophy indexes and provide reference for clinical characteristics analysis of KBD patients. 【Methods】 To investigate the registered KBD patients from KBD areas in Shaanxi Province, we measured the general demographic data of the patients were collected and the ROM of the knee joint (flexion and extension), the ankle joint (dorsiflexion and plantar flexion), and the muscle atrophy related indexes such as the upper arm circumference, thigh circumference, calf circumference and grip strength. According to the population characteristics, i.e., gender, age, body mass index (BMI) and KBD grade, the median and quartile of joint ROM and muscle atrophy of KBD patients were reported, and then the differences in each index among different groups were analyzed. Partial correlation analysis was used to explore the correlation between indicators after controlling for variables such as gender, age and BMI. 【Results】 A total of 480 patients with KBD were investigated in this study, who consisted of 249 (51.9%) males and 231 (48.1%) females, with an average age of (63.10±7.32) years and an average BMI of (23.49±8.90) kg/m2. The knee flexion ROM, knee extension ROM, ankle dorsiflexion ROM and ankle plantar flexion ROM were [105.0 (95.0, 120.0)] °, [0.0 (-15.0, 0.0)] °, [5.0 (0.0, 15.0)] ° and [20.0 (15.0, 30.0)] °, respectively, in KBD patients in Shaanxi Province. The left thigh circumference, right thigh circumference, left calf circumference, right calf circumference, and upper arm circumference were [43.0 (40.0, 47.0)] cm, [43.0 (39.0, 47.0)] cm, [29.0 (27.0, 32.0)] cm, [29.5 (27.0, 32.0)] cm, [27.0 (25.0, 30.0)] cm, respectively. The left hand grip strength and right hand grip strength were [13.4 (9.5, 18.4)] kg and [13.9 (9.8, 18.2)] kg, respectively. With the increase of age, the extension range of the left and right knee joints of KBD patients showed a decreasing trend (H=31.499, 31.847; all P<0.001). The range of motion of bilateral knee flexion was higher in the normal BMI group than in the overweight or obese group, with statistically significant differences (H=7.753, 12.333; P=0.021, 0.002). The knee flexion, thigh circumference, and calf circumference of the left and right sides showed a decreasing trend under different KBD grades (H=14.345, 17.256, 8.000, 8.462, 8.558, 9.633; all P<0.05). Correlation analysis showed that knee flexion ROM was positively correlated with thigh circumference, calf circumference, and grip strength in patients with KBD (all P<0.05). There was a positive correlation between knee extension ROM and thigh circumference in patients with KBD (P<0.01). 【Conclusion】 The impaired joint ROM and muscle atrophy are serious in KBD patients in Shaanxi Province, and there is a correlation between joint motion and muscle atrophy.

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