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1.
J Enzyme Inhib Med Chem ; 39(1): 2292006, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38086769

ABSTRACT

In this study, seventeen isobavachalcone (IBC) derivatives (1-17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50 values of 4.35 and 14.21 µM, respectively. Compared with IBC, compound 16 exhibited up to 4.11-fold enhancement of cytotoxic activity on human non-small cell lung cancer H1975 cells. In addition, we found that compound 16 suppressed H1975 cells via inducing apoptosis and necroptosis. The initial mechanism of compound 16 induced cell death in H1975 cells involves the increasing of Bax/Bcl-2 ratio and Cyt C protein level, down-regulating of Akt protein level, and cleaving caspase-9 and -3 induced apoptosis; the up-regulation of RIP3, p-RIP3, MLKL, and p-MLKL levels induced necroptosis. Moreover, compound 16 also caused mitochondrial dysfunction, thereby decreasing cellular ATP levels, and resulting in excessive reactive oxygen species (ROS) accumulation.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Necroptosis , Apoptosis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Reactive Oxygen Species/metabolism
2.
Chem Pharm Bull (Tokyo) ; 71(11): 798-803, 2023.
Article in English | MEDLINE | ID: mdl-37914257

ABSTRACT

Four new magnolol derivatives were synthesized and evaluated for their in vitro anti-cancer properties. Among these, compound 3 showed the most potent cytotoxic activity against the SMMC-7721, SUN-449, and HepG2 human hepatocellular carcinoma cell lines, with IC50 values of 3.39, 4.11, and 6.88 µM, respectively. Compound 3 also induced apoptosis of SMMC-7721 cells by down-regulating Bcl-2 and Akt protein levels, up-regulating of Bax protein level, and cleaving caspase-9 and -3. In addition, transwell assays showed that compound 3 significantly suppressed the migration and invasion of SMMC-7721 cells, which was confirmed based on the down-regulation of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-2 and -9 (MMP-2, and MMP-9) protein levels.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Matrix Metalloproteinase 2/metabolism , Cell Line, Tumor , Cell Movement , Neoplasm Invasiveness , Apoptosis , Cell Proliferation
3.
Molecules ; 28(17)2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37687063

ABSTRACT

As a biodegradable and renewable material, polylactic acid is considered a major environmentally friendly alternative to petrochemical plastics. Microbial fermentation is the traditional method for lactic acid production, but it is still too expensive to compete with the petrochemical industry. Agro-industrial wastes are generated from the food and agricultural industries and agricultural practices. The utilization of agro-industrial wastes is an important way to reduce costs, save energy and achieve sustainable development. The present study aimed to develop a method for the valorization of Zizania latifolia waste and cane molasses as carbon sources for L-lactic acid fermentation using Rhizopus oryzae LA-UN-1. The results showed that xylose derived from the acid hydrolysis of Z. latifolia waste was beneficial for cell growth, while glucose from the acid hydrolysis of Z. latifolia waste and mixed sugars (glucose and fructose) from the acid hydrolysis of cane molasses were suitable for the accumulation of lactic acid. Thus, a three-stage carbon source utilization strategy was developed, which markedly improved lactic acid production and productivity, respectively reaching 129.47 g/L and 1.51 g/L·h after 86 h of fermentation. This work demonstrates that inexpensive Z. latifolia waste and cane molasses can be suitable carbon sources for lactic acid production, offering an efficient utilization strategy for agro-industrial wastes.


Subject(s)
Molasses , Rhizopus oryzae , Canes , Industrial Waste , Lactic Acid , Carbon , Glucose
4.
J Pain Res ; 16: 2619-2632, 2023.
Article in English | MEDLINE | ID: mdl-37533560

ABSTRACT

Background: Neuropathic pain (NP) is a common and severe problem following spinal cord injury (SCI). However, its relationship with functional outcome remains unclear. Methods: A retrospective explorative analysis was performed on SCI patients admitted to a tertiary academic medical center between January 2018 and June 2022. The candidate predictor variables, including demographics, clinical characteristics and complications, were analyzed with logistic and linear regression. Spinal Cord Independence Measure (SCIM) scores at discharge and mean relative functional gain (mRFG) of SCIM were as outcome parameters. Results: A total of 140 SCI patients included for the final analysis. Among them, 44 (31.43%) patients were tetraplegics, and 96 (68.57%) patients were paraplegics; 68 (48.57%) patients developed NP, and 72 (51.43%) patients did not. Logistic and linear regression analyses of SCIM at discharge both showed that NP [OR=3.10, 95% CI (1.29,7.45), P=0.01; unstandardized ß=11.47, 95% CI (4.95,17.99), P<0.01; respectively] was significantly independent predictors for a favorable outcome (SCIM at discharge ≥ 50, logistic regression results) and higher SCIM total score at discharge (linear regression results). Besides, NP [unstandardized ß=15.67, 95% CI (8.94,22.41), P<0.01] was also independently associated with higher mRFG of SCIM scores. Furthermore, the NP group had significantly higher mRFG, SCIM total scores and subscales (self-care, respiration and sphincter management, and mobility) at discharge compared to the non-NP group. However, there were no significant differences in mRFG, SCIM total score or subscales at discharge among the NP subgroups in terms of locations (at level pain, below level pain, and both) or timing of occurrence (within and after one month after SCI). This study also showed that incomplete injury, lumbar-sacral injury level and non-anemia were significantly independent predictors for a favorable outcome, and higher mRFG of SCIM scores (except for non-anemia). Conclusion: NP appears independently associated with better functional recovery in SCI patients, suggesting the bright side of this undesirable complication. These findings may help to alleviate the psychological burden of NP patients and ultimately restore their confidence in rehabilitation.

5.
Front Neurol ; 14: 1175078, 2023.
Article in English | MEDLINE | ID: mdl-37333013

ABSTRACT

Background: After spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown. Methods: A retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability. Results: The CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0-6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor. Conclusion: The closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery.

6.
Appl Biochem Biotechnol ; 195(1): 623-638, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36114924

ABSTRACT

Aurantiochytrium is a promising source of docosahexaenoic acid (DHA) and carotenoids, but their synthesis is influenced by environmental stress factors. In this study, the effect of different light intensities on the fermentation of DHA oil and carotenoids using Aurantiochytrium sp. TZ209 was investigated. The results showed that dark culture and low light intensity conditions did not affect the normal growth of cells, but were not conducive to the accumulation of carotenoids. High light intensity promoted the synthesis of DHA and carotenoids, but caused cell damage, resulting in a decrease of oil yield. To solve this issue, a light intensity gradient strategy was developed, which markedly improved the DHA and carotenoid content without reducing the oil yield. This strategy produced 30.16 g/L of microalgal oil with 15.11 g/L DHA, 221 µg/g astaxanthin, and 386 µg/g ß-carotene. This work demonstrates that strain TZ209 is a promising DHA producer and provides an efficient strategy for the co-production of DHA oil together with carotenoids.


Subject(s)
Carotenoids , Stramenopiles , Docosahexaenoic Acids , Fermentation , beta Carotene
7.
Sci Total Environ ; 863: 160953, 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36543072

ABSTRACT

Microplastics, defined as particles <5 mm in diameter, are emerging environmental pollutants that pose a threat to ecosystems and human health. Biofilm degradation of microplastics may be an ecologically friendly approach. This review systematically summarises the factors affecting biofilm degradation of microplastics and proposes feasible methods to improve the efficiency of microplastic biofilm degradation. Environmentally insensitive microorganisms were screened, optimized, and commercially cultured to facilitate the practical application of this technology. For strain screening, technology should focus on microorganisms/strains that can modify the hydrophobicity of microplastics, degrade the crystalline zone of microplastics, and metabolise additives in microplastics. The biodegradation mechanism is also described; microorganisms secreting extracellular oxidases and hydrolases are key factors for degradation. Measuring the changes in molecular weight distribution (MWD) enables better analysis of the biodegradation behaviour of microplastics. Biofilm degradation of microplastics has relatively few applications because of its low efficiency; however, enrichment of microplastics in freshwater environments and wastewater treatment plant tailwater is currently the most effective method for treating microplastics with biofilms.


Subject(s)
Microplastics , Water Pollutants, Chemical , Humans , Plastics/analysis , Ecosystem , Biodegradation, Environmental , Water Pollutants, Chemical/analysis , Biofilms , Fresh Water , Environmental Monitoring/methods
8.
J Asian Nat Prod Res ; 25(8): 731-740, 2023.
Article in English | MEDLINE | ID: mdl-36448521

ABSTRACT

AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

9.
Molecules ; 27(20)2022 Oct 11.
Article in English | MEDLINE | ID: mdl-36296386

ABSTRACT

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.


Subject(s)
Antineoplastic Agents , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Reactive Oxygen Species/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Cell Line, Tumor , bcl-2-Associated X Protein , Apoptosis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Adenosine Triphosphate/pharmacology , Cell Proliferation
10.
Neurosci Lett ; 778: 136603, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35364125

ABSTRACT

During neurodevelopment, differentiation of neural stem/progenitor cells (NSPCs) into neurons are regulated by many factors including Notch signaling pathway. Herein, we report the effect of a Notch signaling blocker, i.e. γ -secretase inhibitor (GSI), on this differentiating process, especially on the morphological development. NSPCs were cultured and induced to differentiate with or without GSI. The neurite outgrowth was impeded by GSI application and the expression of a Notch signaling downstream effector miR-342-5p increased with the downregulated expression of Notch effectors Hes1 and Hes5. Upregulated expression of miR-342-5p in differentiating NSPCs could shorten the neurite length of progeny neurons, which was similar to the effect of GSI. To avoid the possible influence from astrocytes into neurons, we directly applied cultured neurons, on which GSI could shorten the processes and RBP-J knockdown could also reduce the neurite length. Similarly, transfection of miR-342-5p mimics or inhibitors into PC12 cells led to shorter or longer processes of cells compared with control ones. Furthermore, in differentiating NSPCs, GSI-induced shorter neurites could be partially rescued by miR-342-5p inhibitors, and STAT3 was one of the possible targets of miR-342-5p during this differentiating process as indicated by results of Western Blot test, luciferase reporter assay and GFP reporter assay. To further demonstrate the role of STAT3, it was introduced into GSI-treated neurons and the GSI-affected neurites could also be partially rescued. In conclusion, GSI could influence the morphological development of neurons and the possible mechanism involved Notch/miR-342-5p and STAT3. These results would be informative for future therapeutic research.


Subject(s)
Gamma Secretase Inhibitors and Modulators , MicroRNAs , Neural Stem Cells , Receptors, Notch , Amyloid Precursor Protein Secretases/metabolism , Animals , Gamma Secretase Inhibitors and Modulators/pharmacology , MicroRNAs/metabolism , Neural Stem Cells/metabolism , Neurons/metabolism , Rats , Receptors, Notch/metabolism , Signal Transduction
11.
Neurol Ther ; 11(2): 679-695, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35174449

ABSTRACT

INTRODUCTION: Stroke is always associated with a difficult functional recovery process. A brain-computer interface (BCI) is a technology which provides a direct connection between the human brain and external devices. The primary aim of this study was to determine whether training with a BCI-controlled robot can improve functions in patients with subacute stroke. METHODS: Subacute stroke patients aged 32-68 years with a course of 2 weeks to 3 months were randomly assigned to the BCI group or to the sham group for a 4-week course. The primary outcome measures were Loewenstein Occupational Therapy Cognitive Assessment (LOCTA) and Fugl-Meyer Assessment for Lower Extremity (FMA-LE). Secondary outcome measures included Fugl-Meyer Assessment for Balance (FMA-B), Functional Ambulation Category (FAC), Modified Barthel Index (MBI), serum brain-derived neurotrophic factor (BDNF) levels and motor-evoked potential (MEP). RESULTS: A total of 28 patients completed the study. Both groups showed a significant increase in mean LOCTA (sham: P < 0.001, Cohen's d =  - 2.972; BCI: P < 0.001, Cohen's d =  - 4.266) and FMA-LE (sham: P < 0.001, Cohen's d =  - 3.178; BCI: P < 0.001, Cohen's d =  - 3.063) scores. The LOCTA scores in the BCI group were 14.89% higher than in the sham group (P = 0.049, Cohen's d =  - 0.580). There were no significant differences between the two groups in terms of FMA-B (P = 0.363, Cohen's d =  - 0.252), FAC (P = 0.363), or MBI (P = 0.493, Cohen's d =  - 0.188) scores. The serum levels of BDNF were significantly higher within the BCI group (P < 0.001, Cohen's d =  - 1.167), and the MEP latency decreased by 3.75% and 4.71% in the sham and BCI groups, respectively. CONCLUSION: Training with a BCI-controlled robot combined with traditional physiotherapy promotes cognitive function recovery, and enhances motor functions of the lower extremity in patients with subacute stroke. These patients also showed increased secretion of BDNF. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR-INR-17012874.

12.
Opt Lett ; 47(4): 917-920, 2022 Feb 15.
Article in English | MEDLINE | ID: mdl-35167558

ABSTRACT

The angle-sensitive photonic bandgap (PBG) is one of the typical features of one-dimensional photonic crystals. Based on the phase-variation compensation effect between the dielectric and hyperbolic metamaterials (HMMs), angle-insensitive PBGs can be realized in photonic hypercrystals. However, since hypercrystals are usually constructed using metal components, these angle-insensitive PBGs are mostly limited to narrow bandwidths in visible range. Here, we replace metal with indium tin oxide (ITO) to construct HMMs in the near-infrared range. In these ITO-based HMMs, we experimentally demonstrate the negative refraction of light in transverse magnetic polarization. With this HMM component, we realize a photonic hypercrystal with an angle-insensitive PBG in the wavelength range of 1.15-2.02 µm. These ITO-based hypercrystals with large angle-insensitive PBGs can find applications in near-infrared reflectors or filters.

13.
Sci Rep ; 11(1): 17067, 2021 08 23.
Article in English | MEDLINE | ID: mdl-34426653

ABSTRACT

This study is to determine the spatial distribution characteristics of Cu and Zn adsorption on the sediments of the estuary of Dianchi Lake, as well as the composite adsorption law of Cu and Zn on combinations of sediment organic matter, metal oxides, and organic-inorganic composites. The relationship between the adsorption contribution of each component of the substance. A static adsorption experiment was applied to the sediments in the estuary of Dianchi Lake. The relationship between adsorption capacity and sediment composition was analyzed through correlation analysis and redundant analysis. The results show that along the direction of the river flow and the vertical depth, the adsorption capacity presents a relatively obvious spatial distribution law; the change trend of sediment component content is not the same as the change trend of Cu and Zn adsorption capacity. The change trend of the sediment component content is not the same as the change trend of the adsorption amount of Cu and Zn, and the compound effect between the components affects the adsorption amount. The adsorption of Cu by the four groups of sediments after different treatments is more in line with the Freundlich isotherm adsorption model; When adsorbing Zn, the untreated and removed organic matter and iron-aluminum oxide group are in good agreement with the Freundlich model, while the organic matter-removed group and the iron-aluminum oxide removal group are more consistent with the Langmuir isotherm adsorption model; The adsorption contribution rate of organic-inorganic composites in sediments is not a simple addition of organic matter and iron-aluminum oxides, but a more complex quantitative relationship.

14.
Molecules ; 26(14)2021 Jul 15.
Article in English | MEDLINE | ID: mdl-34299577

ABSTRACT

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 µM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biphenyl Compounds/chemistry , Biphenyl Compounds/pharmacology , Lignans/chemistry , Lignans/pharmacology , Antineoplastic Agents/chemical synthesis , Biphenyl Compounds/chemical synthesis , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Female , Humans , Lignans/chemical synthesis , Neoplasm Invasiveness/prevention & control , Triple Negative Breast Neoplasms/drug therapy
15.
Inorg Chem ; 60(15): 11081-11089, 2021 Aug 02.
Article in English | MEDLINE | ID: mdl-34242020

ABSTRACT

A CuI-TbIII heterometallic MOF, namely 1·DMF, was obtained via a coordination assembly process of isonicotinic acid with CuI and TbIII. 1·DMF can be switched to 1·MeOH in methanol with a luminescent emission response. Meanwhile, 1·MeOH exhibits a reversible single-crystal transformation to 1·DMF after immersion in DMF. Both MOFs have superior physicochemical stability. The 1·DMF-based biosensor has a remarkable sensing performance toward penicillin.


Subject(s)
Copper/chemistry , Luminescence , Organometallic Compounds/chemistry , Penicillins/analysis , Terbium/chemistry , Density Functional Theory , Models, Molecular , Molecular Conformation , Penicillins/chemistry
16.
Opt Express ; 29(12): 17736-17745, 2021 Jun 07.
Article in English | MEDLINE | ID: mdl-34154050

ABSTRACT

Contrary to conventional Tamm plasmon (TP) absorbers of which narrow absorptance peaks will shift toward short wavelengths (blueshift) as the incident angle increases for both transverse magnetic (TM) and transverse electric (TE) polarizations, here we theoretically and experimentally achieve nonreciprocal absorption in a planar photonic heterostructure composed of an isotropic epsilon-near-zero (ENZ) slab and a truncated photonic crystal for TM polarization. This exotic phenomenon results from the interplay between ENZ and material loss. And the boundary condition across the ENZ interface and the confinement effect provided by the TP can enhance the absorption in the ENZ slab greatly. As a result, a strong and nonreciprocal absorptance peak is observed experimentally with a maximum absorptance value of 93% in an angle range of 60∼70°. Moreover, this TP absorber shows strong angle-independence and polarization-dependence. As the characteristics above are not at a cost of extra nanopatterning, this structure is promising to offer a practical design in narrowband thermal emitter, highly sensitive biosensing, and nonreciprocal nonlinear optical devices.

17.
Stem Cell Res Ther ; 12(1): 372, 2021 06 29.
Article in English | MEDLINE | ID: mdl-34187584

ABSTRACT

BACKGROUND: Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells. METHODS: sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and ß-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0-35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test. RESULTS: We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery. CONCLUSIONS: LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.


Subject(s)
Membrane Proteins , MicroRNAs , Nerve Tissue Proteins , Neural Stem Cells , Spinal Cord Injuries , Wnt-5a Protein , Animals , Cell Differentiation , Female , Mice , MicroRNAs/genetics , Neural Stem Cells/transplantation , Spinal Cord Injuries/genetics , Spinal Cord Injuries/therapy , Wnt-5a Protein/genetics
19.
Pain Ther ; 10(2): 1085-1100, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33866522

ABSTRACT

INTRODUCTION: Central poststroke pain (CPSP) develops commonly after stroke, which impairs the quality of life, mood, and social functioning. Current pharmacological approaches for the treatment of CPSP are not satisfactory. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique which has been recommended for the treatment of chronic CPSP. However, few studies have evaluated the analgesic effects of rTMS in patients with acute neuropathic pain after stroke. METHODS: We evaluated the analgesic effects of rTMS applied over the upper extremity area of the motor cortex (M1) in patients with acute CPSP. Forty patients were randomized to receive either rTMS (10 Hz, 2000 stimuli) (n = 20) or a sham intervention (n = 20) for 3 weeks. The Numeric Rating Scale (NRS), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2, Chinese version), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), brain-derived neurotrophic factor (BDNF) levels, and motor-evoked potentials (MEP) were analyzed at baseline, 3 days, 1 week, 2 weeks, and 3 weeks. RESULTS: Significant treatment-time interactions were found for pain intensity. Compared with the sham group, the NRS and SF-MPQ-2 scores were significantly lower on the seventh day of treatment in the rTMS group (P < 0.001, Cohen's d = 1.302) (P = 0.003, Cohen's d = 0.771), and this effect lasted until the third week (P = 0.001, Cohen's d = 0.860) (P = 0.027, Cohen's d = 0.550). The HAM-A and HAM-D scores did not change in the rTMS group when compared with the sham group (P = 0.341, Cohen's d = 0.224) (P = 0.356, Cohen's d = 0.217). The serum BDNF levels were significantly higher in the treated group (P = 0.048, Cohen's d = -0.487), and the resting motor threshold (RMT) decreased by 163.65%. CONCLUSION: Our findings indicate that rTMS applied over the upper extremity area of the motor cortex can effectively alleviate acute CPSP, possibly by influencing cortical excitability and serum BDNF secretion. TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry of China: Reg. No. ChiCTR-INR-17012880.

20.
Pain Med ; 21(6): 1216-1223, 2020 06 01.
Article in English | MEDLINE | ID: mdl-31722404

ABSTRACT

OBJECTIVES: Central neuropathic pain (CNP) often appears following spinal cord injury (SCI), but current treatments are not always successful. In this study, we evaluated the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) applied over the hand area of the motor cortex in patients with acute CNP after SCI. METHODS: A total of 48 patients with complete or incomplete SCI and acute CNP participated in this study and were randomized to receive either rTMS (10 Hz, 1,500 stimuli; N = 24) or a sham intervention (N = 24) for three weeks. The numeric rating scale (NRS) and Short-Form McGill Pain Questionnaire-2 (Chinese Edition; SF-MPQ-2-CN) were analyzed to assess the degree of pain. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were collected to explore expression influenced by rTMS. Motor-evoked potential (MEP) latency and maximal amplitude were measured to determine neurophysiological changes. The assessments were carried out at baseline (T0), three days (T1), one week (T2), two weeks (T3), and three weeks (T4) after onset of treatment. RESULTS: The analysis showed significant treatment-time interactions for the quality and intensity of pain, as measured by NRS (P < 0.001, η2 = 0.441) and SF-MPQ-2 (P < 0.001, η2 = 0.590). Compared with the sham group, the NRS and SF-MPQ2-CN scores were significantly lower on the third day (P < 0.001, Cohen's d = 1.135; P = 0.006, Cohen's d = 0.616) and after one week (P < 0.001, Cohen's d = 0.846; P = 0.012, Cohen's d = 0.557) of treatment. In addition, the serum levels of BDNF and NGF were significantly higher in the treated group after three weeks (P = 0.015, Cohen's d = 0.539; P = 0.009, Cohen's d = 0.580), and the MEP amplitude increased by 109.59% (P = 0.033, Cohen's d = 0.464). CONCLUSIONS: These findings indicate that 10 Hz rTMS over the hand area of the motor cortex could alleviate acute CNP in the early phase of SCI and could enhance MEP parameters and modulate BDNF and NGF secretion.


Subject(s)
Neuralgia , Spinal Cord Injuries , Analgesics , Humans , Neuralgia/etiology , Neuralgia/therapy , Pain Measurement , Spinal Cord Injuries/complications , Transcranial Magnetic Stimulation
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