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1.
Genomics ; : 110883, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38857813

RESUMO

Pigmented potato tubers are abundant in chlorogenic acid (CGAs), a metabolite with pharmacological activity. This article comprehensively analyzes the metabolome and transcriptome of Pigmented potatoes Huaxingyangyu and Jianchuanhong at four altitudes of 1800 m, 2300 m, 2800 m, and 3300 m. A total of 20 CGAs and intermediate CGA compounds were identified, including 3-o-caffeoylquinic acid, 4-o-caffeoylquinic acid, and 5-o-caffeoylquinic acid. The CGA content in Huaxinyangyu and Jianchuanhong reached its maximum at an altitude of 2800 m and slightly decreased at 3300 m. 48 candidate genes related to the biosynthesis pathway of CGA were screened through transcriptome analysis. Weighted gene co-expression network analysis (WGCNA) identified that Phenylalanine deaminase (PAL), Coumarate-3 hydroxylase (C3H), and Cinnamic acid 4-hydroxylase (C4H) genes and MYB and bHLH transcription factors co-regulate CGA biosynthesis. The results of this study provide valuable information to reveal the changes in CGA components in colored potatoes at different altitudes.

2.
Environ Toxicol ; 39(7): 3833-3845, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38546377

RESUMO

Depleted uranium (DU) retains the radiological toxicities, which accumulates preferentially in the kidneys. Hedgehog (Hh) pathway plays a critical role in tissue injury. However, the role of Hh in DU-induced nephrotoxicity was still unclear. This study was carried out to investigate the effect of Gli2, which was an important transcription effector of Hh signaling, on DU induced nephrotoxicity. To clarify it, CK19 positive tubular epithelial cells specific Gli2 conditional knockout (KO) mice model was exposed to DU, and then histopathological damage and Hh signaling pathway activation was analyzed. Moreover, HEK-293 T cells were exposed to DU with Gant61 or Gli2 overexpression, and cytotoxicity of DU as analyzed. Results showed that DU caused nephrotoxicity accompanied by activation of Hh signaling pathway. Meanwhile, genetic KO of Gli2 reduced DU-induced nephrotoxicity by normalizing biochemical indicators and reducing Hh pathway activation. Pharmacologic inhibition of Gli1/2 by Gant61 reduced DU induced cytotoxicity by inhibiting apoptosis, ROS formation and Hh pathway activation. However, overexpression of Gli2 aggravated DU-induced cytotoxicity by increasing the levels of apoptosis and ROS formation. Taken together, these results revealed that Hh signaling negatively regulated DU-inducted nephrotoxicity, and that inhibition of Gli2 might serve as a promising nephroprotective target for DU-induced kidney injury.


Assuntos
Proteínas Hedgehog , Rim , Camundongos Knockout , Transdução de Sinais , Proteína Gli2 com Dedos de Zinco , Animais , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Humanos , Células HEK293 , Transdução de Sinais/efeitos dos fármacos , Proteína Gli2 com Dedos de Zinco/metabolismo , Proteína Gli2 com Dedos de Zinco/genética , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Camundongos , Urânio/toxicidade , Apoptose/efeitos dos fármacos , Piridinas/farmacologia , Piridinas/toxicidade , Masculino , Nefropatias/induzido quimicamente , Nefropatias/patologia , Nefropatias/metabolismo , Pirimidinas/farmacologia , Pirimidinas/toxicidade , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo
3.
Adv Healthc Mater ; : e2303388, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38537119

RESUMO

Repairing spinal cord injury (SCI) is a global medical challenge lacking effective clinical treatment. Developing human-engineered spinal cord tissues that can replenish lost cells and restore a regenerative microenvironment offers promising potential for SCI therapy. However, creating vascularized human spinal cord-like tissues (VSCT) that mimic the diverse cell types and longitudinal parallel structural features of spinal cord tissues remains a significant hurdle. In the present study, VSCTs are engineered using embryonic human spinal cord-derived neural and endothelial cells on linear-ordered collagen scaffolds (LOCS). Studies have shown that astrocytes and endothelial cells align along the scaffolds in VSCT, supporting axon extension from various human neurons myelinated by oligodendrocytes. After transplantation into SCI rats, VSCT survives at the injury sites and promotes endogenous neural regeneration and vascularization, ultimately reducing scarring and enhancing behavioral functional recovery. It suggests that pre-vascularization of engineered spinal cord tissues is beneficial for SCI treatment and highlights the important role of exogenous endothelial cells in tissue engineering.

4.
BMC Pharmacol Toxicol ; 25(1): 4, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167223

RESUMO

This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model to predict changes in the pharmacokinetics (PK) and pharmacodynamics (PD, PDE4 inhibition) of roflumilast (ROF) and ROF N-oxide when co-administered with eight CYP3A4/1A2 perpetrators. The population PBPK model of ROF and ROF N-oxide has been successfully developed and validated based on the four clinical PK studies and five clinical drug-drug interactions (DDIs) studies. In PK simulations, every ratio of prediction to observation for PK parameters fell within the range 0.7 to 1.5. In DDI simulations, except for tow peak concentration ratios (Cmax) of ROF with rifampicin (prediction: 0.63 vs. observation: 0.19) and with cimetidine (prediction: 1.07 vs. observation: 1.85), the remaining predicted ratios closely matched the observed ratios. Additionally, the PBPK model suggested that co-administration with the three perpetrators (cimetidine, enoxacin, and fluconazole) may use with caution, with CYP3A4 strong inhibitor (ketoconazole and itraconazole) or with dual CYP3A41A2 inhibitor (fluvoxamine) may reduce to half-dosage or use with caution, while co-administration with CYP3A4 strong or moderate inducer (rifampicin, efavirenz) should avoid. Overall, the present PBPK model can provide recommendations for adjusting dosing regimens in the presence of DDIs.


Assuntos
Citocromo P-450 CYP3A , Rifampina , Rifampina/farmacologia , Cimetidina , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Interações Medicamentosas , Óxidos , Modelos Biológicos
6.
Biomater Adv ; 153: 213502, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37352743

RESUMO

Cardiovascular disease (CVD) is one of the important causes of death worldwide. The incidence and mortality rates are increasing annually with the intensification of social aging. The efficacy of drug therapy is limited in individuals suffering from severe heart failure due to the inability of myocardial cells to undergo regeneration and the challenging nature of cardiac tissue repair following injury. Consequently, surgical transplantation stands as the most efficient approach for treatment. Nevertheless, the shortage of donors and the considerable number of heart failure patients worldwide, estimated at 26 million, results in an alarming treatment deficit, with only around 5000 heart transplants feasible annually. The existing major alternatives, such as mechanical or xenogeneic hearts, have significant flaws, such as high cost and rejection, and are challenging to implement for large-scale, long-term use. An organoid is a three-dimensional (3D) cell tissue that mimics the characteristics of an organ. The critical application has been rated in annual biotechnology by authoritative journals, such as Science and Cell. Related industries have achieved rapid growth in recent years. Based on this technology, cardiac organoids are expected to pave the way for viable heart repair and treatment and play an essential role in pathological research, drug screening, and other areas. This review centers on the examination of biomaterials employed in cardiac repair, strategies employed for the reconstruction of cardiac structure and function, clinical investigations pertaining to cardiac repair, and the prospective applications of cardiac organoids. From basic research to clinical practice, the current status, latest progress, challenges, and prospects of biomaterial-based cardiac repair are summarized and discussed, providing a reference for future exploration and development of cardiac regeneration strategies.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Humanos , Materiais Biocompatíveis/uso terapêutico , Miócitos Cardíacos , Organoides
7.
Adv Sci (Weinh) ; 10(7): e2205997, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36646515

RESUMO

High levels of reactive oxygen species (ROS) and inflammation create a complicated extrinsic neural environment that dominates the initial post-injury period after spinal cord injury (SCI). The compensatory pathways between ROS and inflammation limited the efficacy of modulating the above single treatment regimen after SCI. Here, novel "nanoflower" Mn3 O4 integrated with "pollen" IRF-5 SiRNA was designed as a combination antioxidant and anti-inflammatory treatment after SCI. The "nanoflower" and "pollen" structure was encapsulated with a neutrophil membrane for protective and targeted delivery. Furthermore, valence-engineered nanozyme Mn3 O4 imitated the cascade response of antioxidant enzymes with a higher substrate affinity compared to natural antioxidant enzymes. Nanozymes effectively catalyzed ROS to generate O2 , which is advantageous for reducing oxidative stress and promoting angiogenesis. The screened "pollen" IRF-5 SiRNA could reverse the inflammatory phenotype by reducing interferon regulatory factors-5 (IRF-5) expression (protein level: 73.08% and mRNA level: 63.10%). The decreased expression of pro-inflammatory factors reduced the infiltration of inflammatory cells, resulting in less neural scarring. In SCI rats, multifunctional nanozymes enhanced the proliferation of various neuronal subtypes (motor neurons, interneurons, and sensory neurons) and the recovery of locomotor function, demonstrating that the remodeling of the extrinsic neural environment is a promising strategy to facilitate nerve regeneration.


Assuntos
Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Engenharia Tecidual , Animais , Ratos , Antioxidantes , Inflamação/complicações , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , RNA Interferente Pequeno , Traumatismos da Medula Espinal/terapia , Engenharia Tecidual/métodos , Nanotecnologia/métodos
8.
Toxicol In Vitro ; 88: 105553, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36634885

RESUMO

As kinds of porous crystalline compounds, zeolitic imidazolate frameworks (ZIFs) have been developed quickly and attracted considerable attention for use in nano drug delivery systems, which raised concerns about cardiovascular disorders. At the present, the cytotoxic mechanism of ZIFs in cardiovascular disorders was still unclear. Our experiment explored the toxicity of ZIF-8, a typical kind of ZIFs, on human EA.hy926 vascular endothelial cells. The cell viability, ROS formation, apoptosis level, inflammatory response level, wound healing ability and atherosclerosis-related indicators of EA.hy926 endothelial cells were analyzed after ZIF-8 treatment. Meanwhile, we evaluated the ability of antioxidant N-Acetyl-L-cysteine (NAC) to attenuate the toxicity of ZIF-8 on EA.hy926 endothelial cells. As results, NAC attenuated ROS formation, cell apoptosis, LDH formation and endothelial dysfunction caused by ZIF-8. As the Wnt/ß-catenin pathway was involved in endothelial cell dysfunction, we also studied the expression level of ß-catenin and LEF1 in ZIF-8 and/or NAC treated EA.hy926 cells. As expected, ZIF-8 increased the protein expressions of ß-catenin and LEF1in the IC50 group, which was significantly inhibited by co-treatment with NAC. Taken together, this study could help improve our understanding about the mechanism of ZIF-8-induced endothelial cells injury and NAC had therapeutic potential in preventing ZIF-8-associated endothelial dysfunction by wnt/ß-catenin pathway.


Assuntos
Acetilcisteína , Células Endoteliais , beta Catenina , Humanos , Acetilcisteína/farmacologia , beta Catenina/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Via de Sinalização Wnt
9.
Infect Drug Resist ; 15: 6681-6687, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36411755

RESUMO

Objective: To explore the perioperative prophylactic medication, identification of Causative pathogen and the treatment strategy of post-craniotomy intracranial infection (PCII) caused by Corynebacterium. Patients and Methods: A 47-year-old overweight male patient with hypertension, diabetes, cerebral hemorrhage and recalcitrant syphilis was clinically diagnosed with PCII based on cerebrospinal fluid (CSF) routine examination (RT), biochemical test (BT), neuroimaging CT and MRI scans, bacterial culture and identification of CSF and clinical manifestations. The risk factors of PCII and perioperative antibiotic prophylaxis were analyzed based on some reviews. The identification of the Corynebacterium Jeikeium (C. Jeikeium) and Corynebacterium simulans (C. simulans) was confirmed by CSF bacterial culture, antibiotics sensitivity in vitro and Metagenomic next-generation sequencing (mNGS) of pathogenic microorganisms, respectively. In addition, individualized therapy schemes were modified according to antimicrobial susceptibility of pathogens and mNGS of pathogenic microorganisms combined with the pathologic and physiological conditions of patients. The efficacy was evaluated depending on the changes in patients' body temperature, clinical manifestation, CSF RT, BT, and other infection-related indicators. Results: The patient recovered after 5 weeks of individualized comprehensive treatment and was discharged home, no recurrence had been observed for three months. Conclusion: This is likely the first reported case of chronic PCII caused by two species of Corynebacterium simultaneously in high risk patient. The PCII can not be prevented by the perioperative antibiotic prophylaxis recommended by the guidelines, prophylaxis need to be individualized based on the risk of infection and the colonization status of the patient. Causative pathogens can be identified by CSF culture and mNGS of pathogenic microorganisms. A judicious antimicrobial therapy plan should take into account not only the in vitro antimicrobial susceptibility, but also the penetration of the antimicrobial agent into the cerebrospinal fluid. It was an excellent choice to combine intrathecal vancomycin with intravenous linezolid to treat PCII resulted from Corynebacterium.

10.
Biomaterials ; 291: 121884, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36356471

RESUMO

Lung regeneration after acute injury usually depends on stem cell migration and differentiation, and functional alveoli-like tissue and capillary structure formation. The homing of mesenchymal stem cells (MSCs) to injury sites promotes lung repair through damaged cell replacement and anti-inflammatory and anti-fibrotic effects. Here, we aimed to improve therapeutic effects of the endogenous MSCs by increasing their homing efficiency. We have identified a high-affinity leptin receptor (LEPR)-binding peptide using a phage display screening technique, as the LEPR is highly expressed in MSCs. The selected LEPR-binding peptides were modified with a collagen binding peptide for specifically tethering to a collagen scaffold. After implantation of the LEPR-binding peptide functionalized collagen scaffold in a rat model of acute lung injury, the endogenous LEPR+ MSCs were specifically recruited out of circulation to the scaffold, and their retention periods in the damaged area were significantly prolonged. The migrated MSCs in the functional scaffold promoted the differentiation of type Ⅱ alveolar epithelial cells to type Ⅰ alveolar epithelial cells and facilitated alveoli-like tissue and capillary formation, thus improved lung function recovery. These results suggest that tethering the LEPR binding peptides to the collagen scaffold significantly enhanced endogenous MSC recruitment and promoted functional regeneration of injured lung tissue.


Assuntos
Lesão Pulmonar Aguda , Receptores para Leptina , Ratos , Animais , Colágeno , Pulmão , Lesão Pulmonar Aguda/terapia , Peptídeos
11.
Biomaterials ; 288: 121689, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35931574

RESUMO

Spinal cord injury (SCI) represents a central nervous system disaster, resulting in the destruction of spinal cord structure and function and the formation of an adverse microenvironment at the SCI site. Various biomaterial-based therapeutic strategies have been developed to repair SCI by bridging spinal cord lesions. However, constructing a favorable biophysical microenvironment with biomaterials for spinal cord regeneration remains challenging because of the unmatched mechanical and electrical transmission properties with native spinal cords and the supra- or subtherapeutic dose release of biological molecules independent of SCI activity. Herein, we developed a new hydrogel with mechanical properties and conductivities comparable to those of native spinal cords by controlling gelatin and PPy concentrations. To endow the hydrogel with a biological function, glutathione (GSH) was conjugated on the hydrogel through gelatin-derived amine groups and GSH-derived sulfhydryl groups to prepare an MMP-responsive hydrogel with a recombinant protein, GST-TIMP-bFGF. The MMP-responsive conductive hydrogel could release bFGF on-demand in response to the SCI microenvironment and provide a favorable biophysical microenvironment with comparable mechanical and electrical properties to native spinal cords. In SCI model rats, the MMP-responsive bionic mechanical and conductive hydrogel could inhibit MMPs levels, promote axon regeneration and angiogenesis, and improve locomotion function recovery after SCI.


Assuntos
Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Animais , Axônios/patologia , Materiais Biocompatíveis/uso terapêutico , Gelatina/uso terapêutico , Hidrogéis/química , Ratos , Medula Espinal/patologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia
12.
Gastrointest Endosc ; 96(3): 436-444, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35461890

RESUMO

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is widely accepted as a primary treatment modality for dysplastic and early cancerous lesions of the GI tract. However, prolonged procedure time and life-threatening adverse events remain obstacles to the successful treatment of esophageal cancer. This study aimed to compare the efficacy and safety of tunnel ESD (T-ESD) with conventional ESD (C-ESD) for superficial esophageal squamous neoplasms. METHODS: A prospective, multicenter trial was conducted at 5 hospitals in China. Patients with esophageal squamous neoplasms were enrolled and randomly assigned to undergo C-ESD or T-ESD. Randomization was stratified by tumor location and circumference extent (<1/2 or ≥1/2). The primary endpoint was procedure time. RESULTS: Between January and July 2018, 160 patients were enrolled. One hundred fifty-two patients (76 in the C-ESD group and 76 in the T-ESD group) were included in the final analysis. The median procedure time was 47.3 minutes (interquartile range, 31.7-81.3) for C-ESD and 40.0 minutes (interquartile range, 30.0-60.0) for T-ESD (P = .095). However, T-ESD specifically reduced the median procedure time 34.5% (29.5 minutes) compared with C-ESD for lesions ≥1/2 circumference (P < .001). Among the multiple secondary outcomes, muscular injury was less frequent in the T-ESD group compared with the C-ESD group (18.4% vs 38.2%, P = .007), but complete healing of artificial mucosal defect in 1-month follow-up was more common in the T-ESD group than the C-ESD group (95.9% vs 84.7%, P =.026). CONCLUSIONS: Our study suggests that T-ESD results in shorter procedure time, specifically for lesions ≥1/2 circumference of the esophagus. In addition, T-ESD has a better safety profile indicated by less frequent muscular injury and improved healing of artificial mucosal defects caused by ESD procedures. (Clinical trial registration number: NCT03404921.).


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
13.
Front Cell Neurosci ; 16: 841733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281296

RESUMO

Patients were found to experience more pain during their second eye cataract surgery compared with their first eye surgery. This study aimed to explore the inflammatory alterations along time in the fellow eye after the first eye surgery and to reveal the underlying mechanism. Eighty patients with bilateral cataracts were recruited and were divided into four groups based on the time of having the second eye surgery. The second eye aqueous humor samples were collected just before surgery and analyzed by mass spectrometry and PCR array. Cytokine activity was enriched in the aqueous humor of the contralateral eye with granulocyte colony-stimulating factor CSF3 significantly upregulated at both gene and protein levels. Rabbits with or without superior cervical ganglionectomy (SCGx) were subjected to lensectomy to mimic human situations. In both human and rabbit models, the fellow eye CSF3 peaked at 1 week post the first eye surgery. Consistently, more neutrophils were recruited to the contralateral eye aqueous humor. Corneal sensitivity and trigeminal electrophysiology were recorded to imply the pain severity in rats receiving capsulorrhexis with or without SCGx. A more intense pulse was detected in the contralateral trigeminal ganglion after the rat received one eye surgery. SCGx could effectively reduce the fellow corneal sensitivity and trigeminal nerve pain. These alterations were under direct regulation of the sympathetic nerves on the surgical eye side. Our results suggest that CSF3 and sympathetic activity could serve as potential analgesic targets during ocular surgeries.

14.
ACS Nano ; 16(2): 1986-1998, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-34842412

RESUMO

Aligned fibrous hydrogels capable of recruiting endogenous neural stem/progenitor cells (NSPCs) show great promise in spinal cord injury (SCI) repair. However, the hydrogels suffer from severe issues in close contact with the transected nerve stumps and harnessing the NSPC fate in the lesion microenvironment. Herein, we report aligned collagen-fibrin (Col-FB) fibrous hydrogels with stretchable property, adhesive behavior, and stromal cell-derived factor-1α (SDF1α)/paclitaxel (PTX) spatiotemporal delivery capability. The resultant Col-FB fibrous hydrogels exhibited 1.98 times longer elongation at break (230%), 2.55 times lower Young's modulus (17.93 ± 1.16 KPa), and 2.21 times greater adhesive strength (3.45 ± 0.48 KPa) than collagen (Col) fibrous hydrogels. The soft aligned fibrous hydrogels simulate the oriented microstructure and soft tissue feature of a natural spinal cord and provide elasticity and adhesivity to ensure a persistent close contact with host stumps. The repair of complete transection SCI in rats demonstrates that "middle-to-bilateral" SDF1α gradient release induced endogenous NSPC migration to the lesion site in 10 days, and SDF1α/PTX sequential release promoted neuronal differentiation of the recruited NSPCs over 8 weeks, leading to hind limb locomotion recovery. The presented strategy was proved to be efficient for harnessing endogenous NSPCs, which facilitate SCI repair significantly.


Assuntos
Células-Tronco Neurais , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Adesivos , Animais , Diferenciação Celular , Hidrogéis/farmacologia , Ratos , Medula Espinal , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia
15.
Dose Response ; 19(4): 15593258211039931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658683

RESUMO

OBJECTIVE: To study the effects of adaptive response in A549 cells induced by low-dose radiation and the miRNAs expression. METHODS: A549 cells were irradiated with 50 mGy and 200 mGy initial doses, respectively, and then irradiated with a challenge dose 20 Gy at 6 hours interval. The biological effects and miRNA expression were detected. RESULTS: The apoptosis rates of 50 mGy-20 Gy and 200 mGy-20 Gy groups were significantly lower than that of only 20 Gy irradiation group (P < .05). The percentage of G2/M phase cells of 50 mGy-20 Gy and 200 mGy-20 Gy groups was significantly decreased relative to the 20 Gy group (P < .05). One miRNA (mir-3662) was upregulated and 15 miRNAs (mir-185, mir-1908, mir-307, mir-182, mir-92a, mir-582, mi-r501, mir138-5p, mir-1260, mir-484, mir-378d, mir-193b, mir-127-3p, mir-1303, and mir-654-5p) were downregulated both in 50 mGy-20 Gy and 200 mGy-20 Gy groups than that of the 20 Gy group. Go and KEGG enrichment analysis showed that the target genes were significantly enriched in cell communication regulation, metabolic process, enzyme binding, and catalytic activity signaling pathways. CONCLUSION: Low-dose X-ray of 50 mGy and 200 mGy radiation can induce adaptive apoptosis response prior to 20 Gy in A549 cells. Sixteen differently expressed miRNAs may play important roles in the adaptive effect of low-dose radiation.

16.
Stem Cells ; 39(8): 1025-1032, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33657255

RESUMO

Spinal cord injury (SCI) typically results in long-lasting functional deficits, largely due to primary and secondary white matter damage at the site of injury. The transplantation of neural stem cells (NSCs) has shown promise for re-establishing communications between separated regions of the spinal cord through the insertion of new neurons between the injured axons and target neurons. However, the inhibitory microenvironment that develops after SCI often causes endogenous and transplanted NSCs to differentiate into glial cells rather than neurons. Functional biomaterials have been shown to mitigate the effects of the adverse SCI microenvironment and promote the neuronal differentiation of NSCs. A clear understanding of the mechanisms of neuronal differentiation within the injury-induced microenvironment would likely allow for the development of treatment strategies designed to promote the innate ability of NSCs to differentiate into neurons. The increased differentiation of neurons may contribute to relay formation, facilitating functional recovery after SCI. In this review, we summarize current strategies used to enhance the neuronal differentiation of NSCs through the reconstruction of the SCI microenvironment and to improve the intrinsic neuronal differentiation abilities of NSCs, which is significant for SCI repair.


Assuntos
Células-Tronco Neurais , Traumatismos da Medula Espinal , Transplante de Células-Tronco , Diferenciação Celular , Humanos , Células-Tronco Neurais/transplante , Neuroglia/patologia , Neurônios/patologia , Medula Espinal , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia
17.
Adv Healthc Mater ; 10(8): e2001896, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33522126

RESUMO

Spinal cord injury (SCI) is plaguing medical professionals globally due to the complexity of injury progression. Based on tissue engineering technology, there recently emerges a promising way by integrating drugs with suitable scaffold biomaterials to mediate endogenous neural stem cells (NSCs) to achieve one-step SCI repair. Herein, exosomes extracted from human umbilical cord-derived mesenchymal stem cells (MExos) are found to promote the migration of NSCs in vitro/in vivo. Utilizing MExos as drug delivery vehicles, a NSCs migration promoted and paclitaxel (PTX) delivered MExos-collagen scaffold is designed via a novel dual bio-specificity peptide (BSP) to effectively retain MExos within scaffolds. By virtue of the synergy that MExos recruit endogenous NSCs to the injured site, and PTX induce NSCs to give rise to neurons, this multifunctional scaffold has shown superior performance for motor functional recovery after complete SCI in rats by enhancing neural regeneration and reducing scar deposition. Besides, the dual bio-specific peptide demonstrates the capacity of tethering other cells-derived exosomes on collagen scaffold, such as erythrocytes-derived or NSCs-derived exosomes on collagen fibers or membranes. The resulting exosomes-collagen scaffold may serve as a potential multifunctional therapy modality for various disease treatments including SCI.


Assuntos
Exossomos , Células-Tronco Neurais , Preparações Farmacêuticas , Traumatismos da Medula Espinal , Animais , Colágeno , Células-Tronco Neurais/transplante , Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Alicerces Teciduais
18.
J Cell Physiol ; 236(4): 2659-2668, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32869287

RESUMO

A postcataract surgery complication in patients with retinitis pigmentosa (RP) is lens capsular contraction. To identify potential proteins contributing to this phenomenon, high-performance liquid chromatography/mass spectrometry-based proteomic analysis was conducted with aqueous humor samples collected from 11 patients who underwent cataract surgeries, with four patients diagnosed as RP and cataract (RP group) and the other seven with only senile cataract group. The upregulated proteins in the RP group were enriched in wound response, while downregulated proteins were enriched in cell adhesion and lens crystallins. Receptors of two dramatically upregulated proteins tenascin-C (TNC) and serotransferrin were found expressed in human lens epithelial cells (HLEs). TNC can promote primary HLEs proliferation and cell line HLE-B3 migration. This study indicates aqueous humor proteomic analysis serves as an effective way to unveil the pathogenesis of RP complications. TNC is a potential target of stimulating HLEs proliferation in RP concomitant cataract patients that worth further research.


Assuntos
Humor Aquoso/metabolismo , Catarata/metabolismo , Proteoma , Proteômica , Retinose Pigmentar/metabolismo , Idoso , Catarata/diagnóstico , Catarata/etiologia , Catarata/terapia , Extração de Catarata/efeitos adversos , Linhagem Celular , Movimento Celular , Proliferação de Células , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Cápsula do Cristalino/metabolismo , Cápsula do Cristalino/patologia , Doenças do Cristalino/etiologia , Doenças do Cristalino/metabolismo , Doenças do Cristalino/patologia , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Retinose Pigmentar/complicações , Retinose Pigmentar/diagnóstico , Tenascina/genética , Tenascina/metabolismo , Resultado do Tratamento
19.
J Ophthalmol ; 2020: 1780498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377412

RESUMO

Bacteria associated with postoperative endophthalmitis mostly originate from the normal bacterial flora of the patient's conjunctiva and eyelids, so the incidence of endophthalmitis may be reduced by eliminating the ocular and adnexal flora before surgery. We assessed the effectiveness of eyedrops of 0.5% levofloxacin and 5.0% povidone-iodine (PVI) in reducing conjunctival bacterial flora by metagenomic analysis. A total of 2.4 × 106 high-quality sequencing reads were generated from 93 conjunctival samples obtained from 31 eyes scheduled for cataract surgery before prophylactic therapy (group 1), after administration of 0.5% levofloxacin eyedrops into the conjunctival sac 8 times before surgery (group 2), and at 3 minutes after instillation of 5.0% PVI solution in the conjunctival sac (group 3) followed by surgery irrigation. The alpha diversity and beta diversity results demonstrated that group 3 had the least richness and biodiversity. Corynebacterium, Pseudomonas, Staphylococcus, Acinetobacter, and Streptococcus were predominant in all samples. The relative abundance of these bacterial species was 30.94%, 27.48%, 5.26%, 4.55%, and 2.61% in group 1, 16.32%, 44.10%, 2.19%, 5.39%, and 0.97% in group 2, and 5.90%, 65.55%, 0.39%, 5.36%, and 0.10% in group 3, respectively. The most easily and difficultly eliminated were Corynebacterium and Pseudomonas, respectively. In conclusion, the metagenomic analysis using high-throughput sequencing provides a scientific way for evaluating the effectiveness of a disinfection method from the perspective of analyzing the composition and diversity of the conjunctival microbiome. Despite the use of preoperative antisepsis regimens, the ocular surface of patients receiving cataract surgery could not be rendered completely aseptic, indicating that more strict disinfection methods need to be adopted to reduce the risk for anterior chamber contamination and endophthalmitis after cataract surgery.

20.
Sensors (Basel) ; 21(1)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396255

RESUMO

Detection of weeds and crops is the key step for precision spraying using the spraying herbicide robot and precise fertilization for the agriculture machine in the field. On the basis of k-mean clustering image segmentation using color information and connected region analysis, a method combining multi feature fusion and support vector machine (SVM) was proposed to identify and detect the position of corn seedlings and weeds, to reduce the harm of weeds on corn growth, and to achieve accurate fertilization, thereby realizing precise weeding or fertilizing. First, the image dataset for weed and corn seedling classification in the corn seedling stage was established. Second, many different features of corn seedlings and weeds were extracted, and dimensionality was reduced by principal component analysis, including the histogram of oriented gradient feature, rotation invariant local binary pattern (LBP) feature, Hu invariant moment feature, Gabor feature, gray level co-occurrence matrix, and gray level-gradient co-occurrence matrix. Then, the classifier training based on SVM was conducted to obtain the recognition model for corn seedlings and weeds. The comprehensive recognition performance of single feature or different fusion strategies for six features is compared and analyzed, and the optimal feature fusion strategy is obtained. Finally, by utilizing the actual corn seedling field images, the proposed weed and corn seedling detection method effect was tested. LAB color space and K-means clustering were used to achieve image segmentation. Connected component analysis was adopted to remove small objects. The previously trained recognition model was utilized to identify and label each connected region to identify and detect weeds and corn seedlings. The experimental results showed that the fusion feature combination of rotation invariant LBP feature and gray level-gradient co-occurrence matrix based on SVM classifier obtained the highest classification accuracy and accurately detected all kinds of weeds and corn seedlings. It provided information on weed and crop positions to the spraying herbicide robot for accurate spraying or to the precise fertilization machine for accurate fertilizing.


Assuntos
Plântula , Máquina de Vetores de Suporte , Zea mays , Produtos Agrícolas , Plantas Daninhas
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