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1.
Neural Regen Res ; 17(1): 115-121, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100446

RESUMO

Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian populations. Unprotected ears are most often damaged following exposure to blasts. Although there is an association between tympanic membrane perforation and TBI in blast exposure victims, little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear canal. The present study investigated whether exposure to blasts directed through the ear canal causes brain injury in Long-Evans rats. Animals were exposed to a single blast (0-30 pounds per square inch (psi)) through the ear canal, and brain injury was evaluated by histological and behavioral outcomes at multiple time-points. Blast exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain, including increased expression of c-Fos, induction of a profound chronic neuroinflammatory response, and apoptosis of neurons. The blast-induced injury was not limited only to the brainstem most proximal to the source of the blast, but also affected the forebrain including the hippocampus, amygdala and the habenula, which are all involved in cognitive functions. Indeed, the animals exhibited long-term neurological deficits, including signs of anxiety in open field tests 2 months following blast exposure, and impaired learning and memory in an 8-arm maze 12 months following blast exposure. These results suggest that the unprotected ear canal provides a locus for blast waves to cause TBI. This study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center (Animal protocol# 0932E, approval date: September 30, 2016 and 0932F, approval date: September 27, 2019).

2.
J Colloid Interface Sci ; 605: 710-717, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34365307

RESUMO

Wide-bandgap (WBG) perovskites play a crucial role for top cells in tandem solar cells (TSCs), which provides a promising avenue to boost the performance of widely used commercial solar cells. However, such WBG perovskite solar cells (PSCs) show poor performance compared to that of ~1.6 eV bandgap PSCs due to high defects density and photo-instability, resulting in relatively large open-circuit voltage loss (Vloss). Herein, we introduce alkali pseudo-halide KBF4 into the perovskite precursor solution for preparing less-defect WBG perovskite film. It is showed that the interstitial occupancy of K+ in the perovskite lattice and the suppression of recombination by BF4-, thereby inhibiting the ion migration and reducing the trap density. As a result, the champion WBG PSC (Energy gap (Eg), Eg = 1.74 eV) delivers a high open-circuit voltage (VOC) of 1.21 V and a power conversion efficiency (PCE) of 17.49%. This work provides new insight into the defect tolerance upon metal pseudo-halides doping in the WBG perovskite.

3.
Sci Rep ; 11(1): 21404, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725439

RESUMO

The torque distribution is researched under the condition of the centroid position of distributed drive automatic guided vehicle (AGV) with load platform and is uncertain due to the unknown movable load. The whole vehicle model under centroid variation, the efficiency model of the hub motor and the torque distribution control strategy based on a PID neural network are established. A hierarchical controller is designed to accurately ensure the economy and stability of the vehicle. Simulations of the proposed control strategy are conducted, the results show that the total power and lateral deviation distance of the driving wheels are reduced by 17.63% and 61.54% under low load conditions and 15.54% and 61.39% under high load conditions, respectively, compared with those of the driving wheels under the average torque distribution, and the goal of close slip rates of the driving wheels is achieved. A system prototype is developed and tested, and the experimental results agree with the simulation within error permissibility. The margin of error is less than 5.8%, the results demonstrate that the proposed control strategy is effective. This research can provide a theoretical and experimental basis for the torque optimization distribution of distributed drive AGVs under centroid variation conditions.

4.
World J Clin Cases ; 9(29): 8831-8838, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34734063

RESUMO

BACKGROUND: Eosinophilic fasciitis (EF) is a rare disease characterized by inflammation of the fascia with immune system involvement. Failure to promptly diagnose and treat this disease can seriously affect the quality of life of patients. However, no clear and uniform criteria for diagnosis and treatment exist. CASE SUMMARY: In this paper, we report two cases of EF, both of which showed symmetrical limb swelling and rigidity, increased eosinophils in the peripheral blood and bone marrow, increased red blood cell sedimentation rate, increased antinuclear antibody titer, and pathological changes in the tissues such as eosinophil and lymphocyte infiltration. Both patients were treated with hormones and cyclosporine, and showed significant improvements in their conditions. CONCLUSION: EF is an autoimmune disease causing swelling and sclerosis of the fascia and eosinophilia. It is diagnosable by magnetic resonance imaging, positron emission tomography-computed tomography, blood routine tests, and bone marrow puncture. Glucocorticoids and immunosuppressants are effective treatments.

5.
China CDC Wkly ; 3(43): 906-910, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34745689

RESUMO

Introduction: Occupational noise exposure is a widespread issue in the manufacturing industry in China. Since 2019, the National Surveillance System for Occupational Hazards in the workplace was established to understand different occupational hazards, especially occupational noise, in workplaces in China. Methods: Both environmental and individual noise exposure levels were measured for 19,378 enterprises according to the Work Plan for Surveillance of Occupational Hazards in the Workplace (2020) issued by National Health Commission of the People's Republic of China. Median and interquartile range (IQR) were calculated to describe the distribution of the noise exposure level by industry classification, enterprise-scale, and ownership type of the enterprise. Results: Overall, 25.14% of the individual noise exposure samples exceeded the Chinese national standard among the selected enterprises. The overall median of environmental noise exposure level was 82.8 dB(A) in selected enterprises, while the median of individual noise exposure level was 81.3 dB(A). The individual noise exposure level in the manufacture of metal products, manufacture of motor vehicles, mini-sized enterprises, collective enterprises and private enterprises was relatively high. Conclusion: Occupational noise is still one of the occupational hazards that cannot be ignored in the manufacturing industry, especially in mini-sized and private enterprises. The risk of noise exposure in the target industry is still high and will pose a threat to the health of workers.

6.
Can J Gastroenterol Hepatol ; 2021: 5685610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746041

RESUMO

Background: Accurate dyssynergic defecation (DD) diagnosis depends on anorectal physiological tests that are not widely available. Aim: The purpose of this study is to evaluate the diagnostic yield of digital rectal examination (DRE) compared with anorectal physiological tests in diagnosing DD in patients with constipation. Methods: A total of 218 chronic constipation patients who fulfilled the Rome IV diagnostic criteria for functional constipation (FC) and underwent a standardized DRE and high-resolution anorectal manometry (HRAM) test were enrolled in this study. The diagnostic accuracy of DRE compared with HRAM was evaluated, and the agreement between DRE and HRAM was calculated. Furthermore, a comprehensive literature search on PubMed, Web of Science, Cochrane Library, and Embase database was conducted to further elucidate the pooled diagnostic accuracy of DRE in DD patients. Results: A total of 101 patients (46.33%) had a DD pattern using HRAM, while 117 patients (53.67%) were diagnosed without DD. The sensitivity of DRE in diagnosing dyssynergia was 71.3%, and the specificity was 76.1%. There was a moderate agreement between DRE and HRAM for diagnosing DD (κ-coefficient = 0.474, P < 0.001). Meanwhile, six studies (including our study) comprising 964 constipated patients were included in our meta-analysis. The outcomes demonstrated that the AUC was 0.85 (95% CI 0.82-0.88) with 77% summary sensitivity (95% CI 65-86) and 80% summary specificity (95% CI 71-86) to diagnose DD. Conclusions: DRE could be a valuable tool for screening DD. Our study revealed acceptable sensitivity and specificity of DRE in detecting dyssynergia compared with the physiological tests. Meanwhile, our study highlights that DRE remains an important tool in clinical practice.

7.
Pestic Biochem Physiol ; 179: 104958, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802537

RESUMO

Isoxaflutole (IXF), a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, causes injury to crops leading to reductions in grain yield. In order to solve the phytotoxicity caused by IXF, the present work evaluated the protective response of the substituted quinoxaline derivatives as potential safeners on Zea mays. The bioassay results showed that all of the test compounds displayed protection against IXF. In particular, safener I-6 exhibited excellent safener activity against IXF injury via enhancing glutathione (GSH) content, glutathione S transferases (GSTs) and cytochrome P450 monooxygenases (CYP450) activity. The tested compounds induced the activity of CYP450 and GSTs in Z. mays. The physicochemical properties and ADMET properties of safener I-6, benoxacor and diketonitrile (DKN, IXF metabolite) were compared to predict pharmaceutical behavior. The present work demonstrates that the safener I-6 could be considered as a potential candidate for developing novel safeners in the future.


Assuntos
Herbicidas , Herbicidas/toxicidade , Quinoxalinas/toxicidade , Zea mays
8.
Ecotoxicol Environ Saf ; 228: 112953, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34739932

RESUMO

Epidemiological studies have shown that the elevated concentration of particulate matter with aerodynamic diameter less than 10 µm (PM10) is closely related to the increased risk of heart and lung diseases in the population. Natural isoflavone compound biochanin A (BCA) has anti-inflammatory and antioxidant activities, and has efficacy in alleviating lung injury. The objective of this study was to investigate the inhibitory effect of BCA on PM10 induced acute human bronchial epithelial cells injury. The results showed that PM10 decreased intracellular catalase level to 1.19 ± 0.01 nmol/min/mg prot and induce a surge of reactive oxygen species (ROS). It also increased lactate dehydrogenase (LDH) activity by 428.89% and caused the lipid peroxidation phenomenon. PM10 exposure also upregulates the expression of inflammatory cytokines and mediators. However, BCA could interfere with the above changes caused by PM10, inhibit the LDH level to 8.22 ± 0.03 u/mL, and show anti-inflammatory and antioxidant activities. In addition, the phosphatidylinositol 3-kimase (PI3K) /protein kinase B (PKB/Akt) is a key signal pathway in response to PM10 exposure. In this study, PI3K/Akt signaling pathway is seriously affected by PM10 exposure. PI3K/Akt signaling pathway, PI3K, AKT, tensin homolog deleted on chromosome 10 (PTEN), mechanistic target of rapamycin (mTOR) and p53 protein were all inhibited by PM10 exposure, and PI3K/Akt signaling pathway was inactivated. BCA exert anti-damage function by regulating the activation process of PI3K protein, intervening the regulation process of PI3K/Akt by PTEN, and intervening the expression and phosphorylation of downstream Akt protein.

9.
Food Funct ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821227

RESUMO

This work aimed to investigate the effects of a sulfated derivative of Cyclocarya paliurus polysaccharide (SCP3) on cyclophosphamide (CTX)-induced intestinal barrier damage and intestinal microbiota in mice. The results showed that SCP3 increased the intestine antioxidant defense, repaired the intestinal barrier via restoring villi length and crypt depth, and up-regulated the expression of tight junction proteins. Bacterial 16S rRNA sequencing results confirmed that SCP3 dramatically altered the structure of the gut microbiota, increased the diversity of gut microbiota, and regulated the relative abundances of specific bacteria, including increasing the abundances of Bacteroidetes, Firmicutes, Tenericutes, Oscillospira, and Akkermansia, and decreasing the abundances of Proteobacteria and Verrucomicrobia. In conclusion, SCP3 can improve intestinal function in CTX-treated mice via enhancing the intestinal oxidative stress capacity, repairing the intestinal mucosal barrier, and regulating intestinal microorganisms, and this study provides a scientific theoretical basis for the application of SCP3 in the food and pharmaceutical fields.

10.
Int J Biol Macromol ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34813790

RESUMO

A new type of acidic exopolysaccharide (AESP-II) was extracted and separated from the fermentation broth of Cordyceps militaris (C. militaris), which was further purified to elucidate its structural characteristics and immunological activity. AESP-II was confirmed to be an acidic pyranose with a molecular weight of 61.52 kDa, which consisted of mannose, glucuronic acid, rhamnose, galactose acid, N-acetyl-galactosamine, glucose, galactose and arabinose with a molar ratio of 1.07: 5.38: 1: 3.14: 2.23: 15: 6.09: and 4.04. Animal experiment results verified that AESP-II can significantly promote the proliferation of spleen T and B lymphocytes in mice with immune injury caused by cyclophosphamide (CTX). In particular, the promotion of B lymphocytes presented a dose-effect relationship. In addition, the levels of the cytokines IL-2, IL-4, and IFN-γ, which are mainly secreted by T lymphocytes, and immunoglobulin IgG, IgM and IgA, which are mainly secreted by B lymphocytes, were increased after AESP-II treatment. The above results suggest that fluid immunity is involved in the immunomodulatory function of AESP-II. Simultaneously, AESP-II was detected significantly to promote the phosphorylation expression of p38 kinase (p38), extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK) by Western blot, further suggesting that the activation of the MAPK signaling pathway mediates the immunoregulatory function of AESP-II.

11.
Front Neurosci ; 15: 741571, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720863

RESUMO

Vestibular evoked myogenic potentials (VEMP) have been used to assess otolith function in clinics worldwide. However, there are accumulating evidence suggesting that the clinically used sound stimuli activate not only the otolith afferents, but also the canal afferents, indicating canal contributions to the VEMPs. To better understand the neural mechanisms underlying the VEMPs and develop discriminative VEMP protocols, we further examined sound-evoked responses of the vestibular nucleus neurons and the abducens neurons, which have the interneurons and motoneurons of the vestibulo-ocular reflex (VOR) pathways. Air-conducted clicks (50-80 dB SL re ABR threshold, 0.1 ms duration) or tone bursts (60-80 dB SL, 125-4,000 Hz, 8 ms plateau, 1 ms rise/fall) were delivered to the ears of Sprague-Dawley or Long-Evans rats. Among 425 vestibular nucleus neurons recorded in anesthetized rats and 18 abducens neurons recorded in awake rats, sound activated 35.9% of the vestibular neurons that increased discharge rates for ipsilateral head rotation (Type I neuron), 15.7% of the vestibular neurons that increased discharge rates for contralateral head rotation (Type II neuron), 57.2% of the vestibular neurons that did not change discharge rates during head rotation (non-canal neuron), and 38.9% of the abducens neurons. Sound sensitive vestibular nucleus neurons and abducens neurons exhibited characteristic tuning curves that reflected convergence of canal and otolith inputs in the VOR pathways. Tone bursts also evoked well-defined eye movements that increased with tone intensity and duration and exhibited peak frequency of ∼1,500 Hz. For the left eye, tone bursts evoked upward/rightward eye movements for ipsilateral stimulation, and downward/leftward eye movements for contralateral stimulation. These results demonstrate that sound stimulation results in activation of the canal and otolith VOR pathways that can be measured by eye tracking devices to develop discriminative tests of vestibular function in animal models and in humans.

12.
J Inflamm Res ; 14: 5863-5875, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785926

RESUMO

Purpose: Ketoprofen (KETO) is a traditional non-steroidal anti-inflammatory drug (NSAIDs) with good analgesic and antipyretic effects. However, as NASIDs, the toxicity of KETO towards gastrointestinal (GI) system might limit its clinical use. S-propargyl-cysteine (SPRC) is an excellent endogenous H2S donor showed wide application in the field of anti-inflammation, anti-oxidative stress, or even the protection of cardiovascular system through the elevation of endogenous H2S concentration. As recently studies reported, co-administration of H2S donor might potentially mitigate the GI toxicity and relevant side effects induced by series of NSAIDs. Methods: In this study, we established a SPRC and KETO co-encapsulated poly (lactic-co-glycolic acid) microsphere (SK@MS), and its particle size, morphology, storage stability and in vitro release profile were firstly investigated. The elevation of endogenous H2S level of SK@MS was then calculated, and the pharmacodynamic study (anti-inflammation and analgesic effects) of SK@MS, SPRC, and KETO towards adjuvant induced arthritis (AIA) in rats were also studied. Finally, to test the potential side effect, the heart, liver, spleen, lung, kidney, stomach, small intestine, and large intestine were resected from rats and examined by H&E staining. Results: A monodispersed SK@MS could be observed under the SEM, and particle size was calculated around 25.12 µm. The loading efficiency (LE) for SPRC and KETO were 6.67% and 2.64%, respectively, while the encapsulation efficiency (EE) for SPRC and KETO were 37.20% and 68.28%, respectively. SK@MS showed a sustained release of SPRC and KETO in vitro, which was up-to 15 days. SK@MS could achieve a long-term elevation of the H2S concentration in vivo, while SPRC showed an instant H2S elevation and metabolize within 6 h. Interestingly, the KETO did not show any influence on the H2S concentration in vivo. After establishment of AIA model, neither SPRC nor KETO showed scarcely anti-inflammation and anti-nociception effect, while conversely, SK@MS showed an obvious mitigation towards paw edema and pain in AIA rats, which indicated an improved anti-inflammation and anti-nociception effect when co-delivery of SRC and KETO. Besides, low stimulation towards major organs in rats observed in any experimental group. Conclusion: A monodispersed was successfully prepared in this study, and SK@MS showed a sustained SPRC and KETO release in vitro and H2S release in vivo. In the pharmacodynamics study, SK@MS not only exhibited an excellent anti-inflammation and analgesic effects in AIA rats but also showed low stimulation towards rats.

13.
Oncogene ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782718

RESUMO

Bladder cancer (BLCA) is the most common malignant tumor of the urinary system and is characterized by high metastatic rates and poor prognosis. The expression of tight junction protein 1 (TJP1) is associated with bladder cancer invasion; however, the mechanism by which TJP1 affects vasculature remodeling remains unknown. In this study, we found that TJP1 expression correlated with tumor angiogenesis and poor overall survival in clinical samples. Furthermore, TJP1 overexpression promoted tumor angiogenesis in BLCA cells and stimulated recruitment of macrophages to tumors by upregulating CCL2 expression. Mechanistically, TJP1 interacted with TWIST1 and enhanced the transcriptional activity of CCL2. The impairment of tumor angiogenesis caused by knockdown of TJP1 was dramatically rescued by overexpression of TWIST1. Furthermore, TJP1 recruited USP2, which deubiquitinated TWIST1, thereby protecting TWIST1 from proteasome-mediated protein degradation. In conclusion, our results suggest that TJP1 controls angiogenesis in BLCA via TWIST1-dependent regulation of CCL2. We demonstrate that TJP1 functions as a scaffold for the interaction between USP2 and TWIST1 and this may provide potential therapeutic targets in bladder cancer.

14.
Tissue Eng Regen Med ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784013

RESUMO

BACKGROUND: Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma. METHODS: Mice with scleroderma received a single 50 µg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot. RESULTS: HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages. CONCLUSION: We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycin-induced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.

15.
Org Lett ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797080

RESUMO

Herein, we have developed two types of photoredox-catalyzed cascade reactions using diaryliodonium salts for the concise synthesis of norascyronone A and ß-eudesmol. A rationally designed photoredox-catalyzed arylation/cyclization/Friedel-Crafts cascade reaction of enone was exploited to generate the norascyronone polycyclic skeleton. A visible-light-induced radical cyclization/acyloxy-migration reaction was explored to forge the decalin skeleton of eudesmol, and mechanistic studies indicated the reaction was initiated by one-electron oxidation of the enol ester.

16.
Epigenomics ; 13(23): 1867-1883, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34791892

RESUMO

Aim: To explore the N6-methyladenosine (m6A) methylation of mRNAs and its roles in a mouse model of scleroderma. Materials & methods: To evaluate whether the mouse model of scleroderma could meet the experimental requirements, we examined skin tissue specimens by pathological staining and identified the related indicators by quantitative PCR  (qPCR). m6A-tagged mRNAs were identified via m6A epitranscriptomic microarray, and m6A-RNA-immunoprecipitation qPCR and qPCR were performed to confirm microarray data. Results: There were differences in m6A methylation among 843 mRNAs. Further, there were significant differences among Hras, Saa1, Ccl3, Ccl9 and Il1b in terms of methylation and expression. Conclusion: The m6A methylation spectrum in a mouse model of scleroderma may explain the occurrence of scleroderma.

17.
Anal Chem ; 93(45): 14907-14911, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34735132

RESUMO

Exosomes are nanosized extracellular vesicles that have a critical role in intercellular communication and tumor microenvironment regulation. Extensive research has shown that exosomal small RNAs contribute to metastasis in multiple tumor types and that abnormal epigenetic modifications in nucleic acids also have an association with diverse diseases. However, the content of modified nucleosides on exosomal small RNAs has not been quantitatively reported. Because of the trace amounts of exosomes and matrix complexity, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a powerful tool for label-free sensitive and simultaneous determinations of six important modified nucleosides on small RNAs inside exosomes. This system performed well using only approximately 107-108 particles of exosomes to obtain modified nucleoside levels between 0.001 and 0.03, and the most striking result was that the content of m6A in exosomal small RNAs was continuously higher than that in the cells being analyzed. We hope that this conclusion helps establish a greater degree of deciphering accuracy on exosomes, which has considerable application potential in the diagnosis and prognosis of diseases.


Assuntos
Exossomos , RNA , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Epigênese Genética , Exossomos/genética , Espectrometria de Massas em Tandem
18.
J Biophotonics ; : e202100285, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726828

RESUMO

A novel integration of retinal multispectral imaging (MSI), retinal oximetry and laser speckle contrast imaging (LSCI) is presented for functional imaging of retinal blood vessels that could potentially allow early detection or monitoring of functional changes. We designed and built a cost-effective, scalable, retinal imaging instrument that integrates structural and functional retinal imaging techniques, including MSI, retinal oximetry and LSCI. Color fundus imaging was performed with 470 nm, 550 nm and 600 nm wavelength light emitting diode (LED) illumination. Retinal oximetry was performed using 550 nm and 600 nm LED illumination. LSCI of blood flow was performed using 850 nm laser diode illumination at 82 frames per second. LSCI can visualize retinal and choroidal vasculature without requiring exogenous contrast agents and can provide time-resolved information on blood flow, generating a cardiac pulse waveform from retinal vasculature. The technology can rapidly acquire structural MSI images, retinal oximetry and LSCI blood flow information in a simplified clinical workflow without requiring patients to move between instruments. Results from multiple modalities can be combined and registered to provide structural as well as functional information on the retina. These advances can reduce barriers for clinical adoption, accelerating research using MSI, retinal oximetry and LSCI of blood flow for diagnosis, monitoring and elucidating disease pathogenesis.

19.
J Nanobiotechnology ; 19(1): 371, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789285

RESUMO

BACKGROUND: Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood-brain barrier (BBB), resulting in the poor therapeutic outcomes. RESULTS: In this study, the derivatization and dual targeted delivery technologies were used to actively transport antioxidant melatonin (MLT) into the mitochondria of oxidative stress-damaged cells in brain tissues. A mitochondrial targeting molecule triphenylphosphine (TPP) was conjugated to melatonin (TPP-MLT) to increase the distribution of melatonin in intracellular mitochondria with the push of mitochondrial transmembrane potential. Then, TPP-MLT was encapsulated in dual targeted micelles mediated by TGN peptide (TGNYKALHPHNG) with high affinity for BBB and SHp peptide (CLEVSRKNG) for the glutamate receptor of oxidative stress-damaged neural cells.TGN/SHp/TPP-MLT micelles could effectively scavenge the overproduced ROS to protect neuronal cells from oxidative stress injury during CIS occurrence, as reflected by the improved infarct volume and neurological deficit in CIS model animals. CONCLUSIONS: These promising results showed this stepwise-targeting drug-loaded micelles potentially represent a significant advancement in the precise treatment of CIS.

20.
Oral Dis ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773344

RESUMO

Accumulated evidence indicates that immune cell populations play pivotal roles in the process of tumor initiation, progression, recurrence, metastasis, and immune escape. Ferroptosis is a form of regulating cell death in the nexus between metabolism, redox biology, and human health. Ferroptosis is considered as a vital important event in HNSCC, but the underling mechanism of regulating immune cell populations remains poorly understood. Our tissue microarray study showed that patients with high expression of GPX4 were related to poor survival. Moreover, the expression of GPX4 has been negatively associated with immunogenic cell death-related protein calreticulin in HNSCC tissue cohort. Further, RSL3 was used to induce ferroptosis in HNSCC xenograft of C3H/He mouse. We found that the occurrence of ferroptosis had significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and tumor-associated M2-like macrophages (M2 TAMs) in tumor microenvironment. Meanwhile, the tumor-infiltrating CD4+ and CD8+ T cells were increased. And the calreticulin and HMGB1 may be potential candidate proteins improving the immunosuppressive tumor microenvironment. Taken together, our project suggests that ferroptosis can promote anti-tumor immune response by reversing immunosuppressive microenvironment, indicating that ferroptosis inducer is a promising therapeutic strategy in HNSCC.

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