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1.
Neural Regen Res ; 17(1): 130-136, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100448

RESUMO

Our previous study showed that cell cycle exit and neuronal differentiation 1 (CEND1) may participate in neural stem cell cycle exit and oriented differentiation. However, whether CEND1-transfected neural stem cells can improve the prognosis of traumatic brain injury remained unclear. In this study, we performed quantitative proteomic analysis and found that after traumatic brain injury, CEND1 expression was downregulated in mouse brain tissue. Three days after traumatic brain injury, we transplanted CEND1-transfected neural stem cells into the area surrounding the injury site. We found that at 5 weeks after traumatic brain injury, transplantation of CEND1-transfected neural stem cells markedly alleviated brain atrophy and greatly improved neurological function. In vivo and in vitro results indicate that CEND1 overexpression inhibited the proliferation of neural stem cells, but significantly promoted their neuronal differentiation. Additionally, CEND1 overexpression reduced protein levels of Notch1 and cyclin D1, but increased levels of p21 in CEND1-transfected neural stem cells. Treatment with CEND1-transfected neural stem cells was superior to similar treatment without CEND1 transfection. These findings suggest that transplantation of CEND1-transfected neural stem cells is a promising cell therapy for traumatic brain injury. This study was approved by the Animal Ethics Committee of the School of Biomedical Engineering of Shanghai Jiao Tong University, China (approval No. 2016034) on November 25, 2016.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34851014

RESUMO

Mitochondrial function in cells declines with aging and with neurodegeneration, due in large part to accumulated mutations in mitochondrial DNA (mtDNA) that arise from deficient DNA repair. However, measuring this repair activity is challenging. Here we employ a molecular approach for visualizing mitochondrial base excision repair (BER) activity in situ by use of a fluorescent probe ( UBER ) that reacts rapidly with AP sites resulting from BER activity. Administering the probe to cultured cells revealed signals that were localized to mitochondria, enabling selective observation of mtDNA BER intermediates. The probe showed elevated DNA repair activity under oxidative stress, and responded to suppression of glycosylase activity. Furthermore, the probe illuminated the time lag between the initiation of oxidative stress and the initial step of BER. Absence of MTH1 in cells resulted in elevated demand for BER activity upon extended oxidative stress, while the absence of OGG1 activity limited glycosylation capacity.

3.
Nat Biotechnol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764491

RESUMO

Endocannabinoids (eCBs) are retrograde neuromodulators with important functions in a wide range of physiological processes, but their in vivo dynamics remain largely uncharacterized. Here we developed a genetically encoded eCB sensor called GRABeCB2.0. GRABeCB2.0 consists of a circular-permutated EGFP and the human CB1 cannabinoid receptor, providing cell membrane trafficking, second-resolution kinetics with high specificity for eCBs, and shows a robust fluorescence response at physiological eCB concentrations. Using GRABeCB2.0, we monitored evoked and spontaneous changes in eCB dynamics in cultured neurons and acute brain slices. We observed spontaneous compartmentalized eCB transients in cultured neurons and eCB transients from single axonal boutons in acute brain slices, suggesting constrained, localized eCB signaling. When GRABeCB2.0 was expressed in the mouse brain, we observed foot shock-elicited and running-triggered eCB signaling in the basolateral amygdala and hippocampus, respectively. In a mouse model of epilepsy, we observed a spreading wave of eCB release that followed a Ca2+ wave through the hippocampus. GRABeCB2.0 is a robust probe for eCB release in vivo.

4.
J Clin Lab Anal ; : e24047, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34761437

RESUMO

BACKGROUND: Long non-coding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand 1 (lnc-KCNQ1OT1) represses inflammation and multiple organ dysfunction, whereas its clinical value in sepsis is unclear. Thus, this study aimed to explore this issue. METHODS: Lnc-KCNQ1OT1 from peripheral blood mononuclear cells were detected by RT-qPCR in 116 sepsis patients and 60 healthy controls (HCs). Moreover, sepsis patients were followed-up until death or up to 28 days. RESULTS: Lnc-KCNQ1OT1 decreased in patients with sepsis than in HCs (p < 0.001). In sepsis patients, lnc-KCNQ1OT1 was negatively correlated with sequential organ failure assessment (SOFA) scores (r = -0.344, p < 0.001) and several SOFA subscale scores (including respiratory system, coagulation, liver, and renal systems) (all r < 0, p < 0.05). Furthermore, lnc-KCNQ1OT1 was negatively correlated with CRP (r = -0.386, p < 0.001), TNF-α (r = -0.332, p < 0.001), IL-1ß (r = -0.319, p < 0.001), and IL-6 (r = -0.255, p = 0.006). Additionally, lnc-KCNQ1OT1 levels were lower in sepsis deaths than in sepsis survivors (p < 0.001), and the receiver operating characteristic curve showed that lnc-KCNQ1OT1 had an acceptable ability to predict 28-day mortality (area under the curve: 0.780, 95% confidence interval: 0.678-0.882). Meanwhile, its ability to predict 28-day mortality risk was higher than that of CRP, TNF-α, IL-1ß, and IL-6, but slightly lower than the SOFA score and acute physiology and chronic health evaluation II score. CONCLUSION: Lnc-KCNQ1OT1 serves as a potential biomarker for monitoring disease severity and prognosis in patients with sepsis.

5.
Orthop Surg ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750972

RESUMO

OBJECTIVE: To evaluate the outcomes of cervical spondylotic radiculopathy secondary to bony foraminal stenosis treated with anterior cervical discectomy and fusion (ACDF) combined with anterior cervical foraminotomy (ACF) assisted by High-Definition 3-Dimensional Exoscope. METHODS: In this retrospective study, a total of 19 consecutive patients (12 males and seven females, with an average of 49.2 years, range from 40 to 59 years) with spondylotic radiculopathy caused by bony foraminal stenosis underwent ACDF combined with ACF assisted by High-Definition 3-Dimensional Exoscope in our hospital between January 2019 and December 2019 were included in this study. All patients signed the consent form before the surgery. The patient baseline information such as gender, age, body mass index (BMI), surgery time, blood loss, hospital stay, lesion segment, side, follow-up time and postoperative complications were recorded. The Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), and Visual Analogue Scale (VAS) were measured and compared before surgery, 1 months and final follow-up after surgery. The radiographic outcomes were evaluated using the C2 -C7 angel, disc height, foraminal height, superior diagonal distance, inferior diagonal distance, and foraminal area. RESULTS: The involved levels included C4 -C5 (six cases), C5 -C6 (10 cases), C6 -C7 (three cases). The mean duration of the surgery, mean blood loss, mean hospital stay, and mean follow-up were 100 ± 11.10 min, 19.4 ± 7.05 mL, 7.1 ± 0.99 days, and 12.1 ± 2.25 months, respectively. The average preoperative JOA score was 11.9 ± 1.31, then improved to 15.7 ± 0.73 (t = -13.45, P < 0.001) and 16.2 ± 0.74 (t = -14.39, P < 0.001) at 1 month after operation and at last follow-up, respectively. The average preoperative NDI score was 27.3 ± 3.36, then decreased to 5.1 ± 1.79 (t = 20.63, P < 0.001) and 4.5 ± 1.21 (t = 25.53, P < 0.001) 1 month after operation and at last follow-up, respectively. The average preoperative VAS score was 6.7 ± 0.93, then decreased to 2.4 ± 0.69 (t = 15.05, P < 0.001) and 1.9 ± 0.78 (t = 16.40, P < 0.001) 1 month after operation and at last follow-up, respectively. As compared with the condition before surgery, there was a significant improvement in the C2 -C7 angel, disc height, foraminal height, and foraminal area (P < 0.05). None of the patients developed postoperative vascular injury, nerve injury, loosening and rupture of the internal fixation, displacement of interbody fusion cage, and pseudarthrosis. CONCLUSION: ACDF combined with ACF assisted by High-Definition 3-Dimensional Exoscope is effective and safe for the treatment of CSR caused by secondary to bony foraminal stenosis.

6.
BMC Oral Health ; 21(1): 585, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798867

RESUMO

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most difficult malignancies to control. It displays particular and aggressive behaviour even at an early stage. The purpose of this paper is to explore the value of radiomics based on magnetic resonance fat-suppressed T2-weighted images in predicting the degree of pathological differentiation of TSCC. METHODS: Retrospective analysis of 127 patients with TSCC who were randomly divided into a primary cohort and a test cohort, including well-differentiated, moderately differentiated and poorly differentiated. The tumour regions were manually labelled in fat-suppressed T2-weighted imaging (FS-T2WI), and PyRadiomics was used to extract radiomics features. The radiomics features were then selected by the least absolute shrinkage and selection operator (LASSO) method. The model was established by the logistic regression classifier using a 5-fold cross-validation method, applied to all data and evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity. RESULTS: In total, 1132 features were extracted, and seven features were selected for modelling. The AUC in the logistic regression model for well-differentiated TSCC was 0.90 with specificity and precision values of 0.92 and 0.78, respectively, and the sensitivity for poorly differentiated TSCC was 0.74. CONCLUSIONS: The MRI-based radiomics signature could discriminate between well-differentiated, moderately differentiated and poorly differentiated TSCC and might be used as a biomarker for preoperative grading.

7.
Front Psychiatry ; 12: 772068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790139

RESUMO

Introduction: Sleep disorders (SLD) are supposed to be associated with increased risk and development of Alzheimer's disease (AD), and patients with AD are more likely to show SLD. However, neurobiological performance of patients with both AD and SLD in previous studies is inconsistent, and identifying specific patterns of the brain functional network and structural characteristics in this kind of comorbidity is warranted for understanding how AD and SLD symptoms interact with each other as well as finding effective clinical intervention. Thus, the aims of this systematic review were to summarize the relevant findings and their limitations and provide future research directions. Methods: A systematic search on brain functional and structural changes in patients with both AD and SLD was conducted from PubMed, Web of Science, and EMBASE databases. Results: Nine original articles published between 2009 and 2021 were included with a total of 328 patients with comorbid AD and SLD, 367 patients with only AD, and 294 healthy controls. One single-photon emission computed tomography study and one multislice spiral computed tomography perfusion imaging study investigated changes of cerebral blood flow; four structural magnetic resonance imaging (MRI) studies investigated brain structural changes, two of them used whole brain analysis, and another two used regions of interest; two resting-state functional MRI studies investigated brain functional changes, and one 2-deoxy-2-(18F)fluoro-d-glucose positron emission tomography (18F-FDG-PET) investigated 18F-FDG-PET uptake in patients with comorbid AD and SLD. Findings were inconsistent, ranging from default mode network to sensorimotor cortex, hippocampus, brain stem, and pineal gland, which may be due to different imaging techniques, measurements of sleep disorder and subtypes of AD and SLD. Conclusions: Our review provides a systematic summary and promising implication of specific neuroimaging dysfunction underlying co-occurrence of AD and SLD. However, limited and inconsistent findings still restrict its neurobiological explanation. Further studies should use unified standards and comprehensive brain indices to investigate the pathophysiological basis of interaction between AD and SLD symptoms in the development of the disease spectrums.

8.
Chin J Integr Med ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34816366

RESUMO

OBJECTIVE: To observe the influence of acupuncture on microcirculation perfusion of the pericardium meridian and heart in acute myocardial ischemia (AMI) rats and evaluate whether acupuncture can simultaneously affect the meridians and corresponding viscera. Additionally, acupoints at different meridians were compared and whether they exert the same effects was discussed. METHODS: Totally 32 Sprague-Dawley rats were subjected to left anterior descending (LAD) ligation to develop an AMI model. Rats were divided into 4 groups, including AMI, acupuncture Neiguan (PC 6), Lieque (LU 7) and Qiansanli (LI 10) groups (n=8). Eight rats received only thoracotomy (sham-operated group). The rats in the acupuncture groups received manual acupuncture at PC 6, LU 7 and LI 10 acupoints for 15 min, respectively. The microcirculation perfusion of pericardium meridian and heart was monitored by laser speckle perfusion imager (LSPI) before, during and after acupuncture manipulation for 15 min. Subsequently, the perfusion unit (PU) was calculated and analyzed by PSI System. RESULTS: After LAD, compared to pre-acupuncture stage, the heart microcirculation perfusion (HMP) in the AMI group decreased continuously at during-acupuncture (P>0.05) and post-acupuncture stages (P<0.05), and the pericardium meridian microcirculation perfusion (PMP) showed no significant differences at 3 stages (P>0.05). Compared to pre-acupuncture stage, the PMP and HMP in PC 6 group significantly increased during acupuncture manipulation (both P<0.05), and PMP decreased obviously after acupuncture (P<0.05). The PMP in the LU 7 and LI 10 groups were slightly elevated (both P>0.05); however, they were significantly reduced after acupuncture manipulation (both P<0.05). Additionally, HMP of LI 10 group was decreased significantly during acupuncture, especially compared to pre-acupuncture stage (P<0.05). CONCLUSIONS: Acupuncture at PC 6 obviously increased the PMP and HMP in AMI rats, and the effects were superior to at LU 7 and LI 10 acupoints. It was further confirmed that acupuncture promoted qi and blood circulation, indicating that acupoint specificity exists and features a meridian-propagated effect.

9.
Appl Environ Microbiol ; : AEM0221921, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34818098

RESUMO

As the most abundant D-amino acid (DAA) in the ocean, D-alanine (D-Ala) is a key component of peptidoglycan in bacterial cell wall. However, the underlying mechanisms of bacterial metabolization of D-Ala through microbial food web remain largely unknown. In this study, the metabolism of D-Ala by marine bacterium Pseudoalteromonas sp. CF6-2 was investigated. Based on genomic, transcriptional and biochemical analyses combined with gene knockout, D-Ala aminotransferase was found to be indispensable for the catabolism of D-Ala in strain CF6-2. Investigation on other marine bacteria also showed that D-Ala aminotransferase gene is a reliable indicator for their ability to utilize D-Ala. Bioinformatic investigation revealed that D-Ala aminotransferase sequences are prevalent in genomes of marine bacteria and metagenomes, especially in seawater samples, and Gammaproteobacteria represents the predominant group containing D-Ala aminotransferase. Thus, Gammaproteobacteria is likely the dominant group to utilize D-Ala via D-Ala aminotransferase to drive the recycling and mineralization of D-Ala in the ocean. IMPORTANCE As the most abundant D-amino acid in the ocean, D-Ala is a component of marine DON (Dissolved organic nitrogen) pool. However, the underlying mechanism of bacterial metabolization of D-Ala to drive the recycling and mineralization of D-Ala in the ocean is still largely unknown. The results in this study showed that D-Ala aminotransferase is specific and indispensable for D-Ala catabolism in marine bacteria, and that marine bacteria containing D-Ala aminotransferase genes are predominantly Gammaproteobacteria widely distributed in global oceans. This study reveals marine D-Ala utilizing bacteria and the mechanism of their metabolization of D-Ala. The results shed light on the mechanisms of recycling and mineralization of D-Ala driven by bacteria in the ocean, which are helpful in understanding oceanic microbial-mediated nitrogen cycle.

11.
Front Surg ; 8: 721545, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616768

RESUMO

Objectives: To compare the performance and outcomes of monopolar electrosurgical conization (MESC) or the loop electrosurgical excision procedure (LEEP) in the treatment of high-grade squamous intraepithelial lesion (HSIL). Methods: This retrospective study included 554 patients diagnosed with HSIL through biopsy. The study used either LEEP or MESC for cervical conization. Additionally, the medical records of these patients, including the basic information, status of the excision margin, cone depth, cone width, fragmentation, complication, and the results of a 6-month follow-up after conization, were reviewed. Results: Compared to MESC, LEEP had a significantly higher rate of positive endocervical margin (3.77 vs. 8.65%; p = 0.018), burn injury of the margin (4.90 vs. 10.38%; p = 0.016) and a lower rate of adequate cone depth (83.40 vs. 89.62%; p = 0.034). In addition, LEEP was significantly more likely to cause fragmentation (p = 0.000). There was, however, no significant difference in the rate of abnormal cervical cytology and positive high-risk HPV (hrHPV) between these two groups, 6 months after cervical conization. Conclusion: Both LEEP and MESC appeared to be equally effective in the clinical treatment of HSIL. Nonetheless, MESC resulted in a better pathological outcome with regard to the status of the margin, tissue fragmentation, and cone depth.

12.
Front Oncol ; 11: 635731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631513

RESUMO

Hepatocellular carcinoma (HCC) is one of most prevalent cancer and is a serious healthcare issue worldwide. Portal vein tumor thrombus (PVTT) is a frequent complication and remains as the blockage in the treatment of HCC with high recurrence rate and poor prognosis. There is still no global consensus or standard guideline on the management of HCC with PVTT. In western countries, Sorafenib and Lenvatinib are recommended as the first-line treatment options for HCC patients with PVTT where this condition is now regarded as BCLC Stage C regardless of PVTT types. However, there is growing evidence that supports the close relationship of the extent of PVTT to the prognosis of HCC. Besides the targeted therapy, more aggressive treatment modalities have been proposed and practiced in the clinic which may improve the prognosis of HCC patients with PVTT and prolong the patients' survival time, such as transarterial chemoembolization, radiotherapy, hepatic resection, liver transplantation, and various combination therapies. Herein, we aim to review and summarize the advances in the treatment of HCC with PVTT.

13.
Adv Mater ; : e2105962, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610186

RESUMO

Reversible lithium (Li) plating/stripping is essential for building practical high-energy-density batteries based on Li metal chemistry, which unfortunately remains a severe challenge. In this contribution, it is demonstrated that through the rational regulation of strong Li+ -anion coordination structures in a highly compatible low-polarity solvent, 2-methyl tetrahydrofuran, the Li plating/stripping assisted by a nucleation modulation procedure delivers a remarkably high average Coulombic efficiency under rather demanding conditions (99.7% and 99.5% under 1.0 mA cm-2 , 3.0 mAh cm-2 and 3.0 mA cm-2 , 3.0 mAh cm-2 , respectively). The exceedingly reversible cycling obtained herein is fundamentally correlated with the flattened Li deposition and minimized solid electrolyte interphase (SEI) generation/reconstruction in the customized condition, which notably restrains the growth rates of both dead Li0 (0.0120 mAh per cycle) and SEI-Li+ (0.0191 mAh per cycle) during consecutive cycles. Benefiting from the efficient Li plating/stripping manner, the assembled anode-free Cu|LiFePO4 (2.7 mAh cm-2 ) coin and pouch cells exhibit impressive capacity retention of 43.8% and 41.6% after 150 cycles, respectively, albeit with no optimization on the test conditions. This work provides guidelines into the targeted interfacial design of high-efficiency working Li anodes, aiming to pave the way for the practical deployment of high-energy-density Li metal batteries.

14.
Front Nutr ; 8: 728880, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692744

RESUMO

Background: The association between vitamin C and metabolic syndrome (MetS) has been evaluated in several epidemiological studies with conflicting results. This meta-analysis was therefore employed to further investigate the above issue. Methods: The observational studies on the associations of dietary and circulating (serum and plasma) vitamin C levels with MetS were searched in the PubMed, Web of Science, and Embase database up to April 2021. The pooled relative risk (RR) of MetS for the highest vs. lowest dietary and circulating vitamin C levels and the standard mean difference (SMD) of dietary and circulating vitamin C levels for MetS vs. control subjects were calculated, respectively. Results: A total of 28 observational studies were identified in this meta-analysis. Specifically, 23 studies were related to the dietary vitamin C level. The overall multivariable-adjusted RR demonstrated that the dietary vitamin C level was inversely associated with MetS (RR = 0.93, 95% CI: 0.88-0.97; P = 0.003). Moreover, the overall combined SMD showed that the dietary vitamin C level in MetS was lower than that in control subjects (SMD = -0.04, 95% CI: -0.08 to -0.01; P = 0.024). With regard to the circulating vitamin C level, 11 studies were included. The overall multivariable-adjusted RR demonstrated that the circulating vitamin C level was inversely associated with MetS (RR = 0.60, 95% CI: 0.49-0.74; P < 0.001). In addition, the overall combined SMD showed that the circulating vitamin C level in MetS was lower than that in control subjects (SMD=-0.82, 95%CI: -1.24 to -0.40; P < 0.001). Conclusions: Current evidence suggests that both dietary and circulating vitamin C level is inversely associated with MetS. However, due to the limitation of the available evidence, more well-designed prospective studies are still needed.

15.
BMC Genomics ; 22(1): 740, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649514

RESUMO

BACKGROUND: Mollusca, a phylum of highly rich species, possess vivid shell colours, but the underlying molecular mechanism remains to be elucidated. DNA methylation, one of the most common epigenetic modifications in eukaryotes, is believed to play a vital role in various biological processes. However, analysis of the effects of DNA methylation on shell colouration has rarely been performed in molluscs, limiting the current knowledge of the molecular mechanism of shell colour formation. RESULTS: In the present study, to reveal the role of epigenetic regulation in shell colouration, WGBS, the "gold standard" of DNA methylation analysis, was first performed on the mantle tissues of Yesso scallops (Patinopecten yessoensis) with different shell colours (brown and white), and DNA methylomes at single-base resolution were generated. About 3% of cytosines were methylated in the genome of the Yesso scallop. A slight increase in mCG percentage and methylation level was found in brown scallops. Sequence preference of nearby methylated cytosines differed between high and low methylation level sites and between the brown- and white-shelled scallops. DNA methylation levels varied among the different genomic regions; all the detected regions in the brown group exhibited higher methylation levels than the white group. A total of 41,175 DMRs (differentially methylated regions) were detected between brown and white scallops. GO functions and pathways associated with the biosynthesis of melanin and porphyrins were significantly enriched for DMRs, among which several key shell colour-related genes were identified. Further, different correlations between mRNA expression levels and DNA methylation status were found in these genes, suggesting that DNA methylation regulates shell colouration in the Yesso scallop. CONCLUSIONS: This study provides genome-wide DNA methylation landscapes of Yesso scallops with different shell colours, offering new insights into the epigenetic regulatory mechanism underlying shell colour.


Assuntos
Metilação de DNA , Pectinidae , Animais , Epigênese Genética , Genoma , Pectinidae/genética , Sulfitos
16.
Spinal Cord ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34628476

RESUMO

STUDY DESIGN: Experimental animal study. OBJECTIVES: To assess the feasibility of a custom-designed parallel-moving (PM) clip, compared with a single-axle-lever (SAL) clip, for the development of a compressional spinal cord injury (SCI) model in rats. SETTING: Hospital laboratory in China. METHODS: We used a PM clip and a SAL clip with same compression rate, to develop a SCI model in rats, and set a sham group as a blank control. Within 3 weeks, each group of rats was evaluated for behavioral (Basso-Beattie-Bresnahan locomotor rating score, BBB), and electrophysiological changes (somatosensory evoked potential), and historical staining to observe the differences between the three groups. In particular, the mechanical results of the PM group were calculated. RESULTS: The BBB scores for the SAL and PM groups were significantly lower than those for the sham group (P < 0.05), no significant difference between the two methods (P > 0.05), but the values corresponding to the PM group had smaller standard deviations. The interpeak-latency (IPL) was significantly prolonged (P < 0.0001) and the peak-peak amplitude (PPA) was significantly reduced (P < 0.01) in SAL and PM groups than those in the sham group, but there was no statistical difference in both IPL and PPA between the two SCI groups (P > 0.05). Histological staining showed obvious pathological changes in two SCI groups, and the shape of the lesion zone in the PM group was more symmetrical than that in the SAL groups. CONCLUSIONS: The use of a compressional SCI model in rats with the PM clip we designed is an appropriate method to quantify the injury. The degree of the injury caused by this clip is more stable and uniform than those with classical methods.

17.
Nat Commun ; 12(1): 6021, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654818

RESUMO

The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remain poorly understood. Here, we generate a metabolome atlas of the aging wildtype mouse brain from 10 anatomical regions spanning from adolescence to old age. We combine data from three assays and structurally annotate 1,547 metabolites. Almost all metabolites significantly differ between brain regions or age groups, but not by sex. A shift in sphingolipid patterns during aging related to myelin remodeling is accompanied by large changes in other metabolic pathways. Functionally related brain regions (brain stem, cerebrum and cerebellum) are also metabolically similar. In cerebrum, metabolic correlations markedly weaken between adolescence and adulthood, whereas at old age, cross-region correlation patterns reflect decreased brain segregation. We show that metabolic changes can be mapped to existing gene and protein brain atlases. The brain metabolome atlas is publicly available ( https://mouse.atlas.metabolomics.us/ ) and serves as a foundation dataset for future metabolomic studies.


Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Metaboloma , Animais , Cerebelo/metabolismo , Feminino , Masculino , Redes e Vias Metabólicas , Metabolômica , Camundongos , Esfingolipídeos
18.
Aging (Albany NY) ; 13(20): 23471-23516, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34718232

RESUMO

It is widely thought that individuals age at different rates. A method that measures "physiological age" or physiological aging rate independent of chronological age could therefore help elucidate mechanisms of aging and inform an individual's risk of morbidity and mortality. Here we present machine learning frameworks for inferring individual physiological age from a broad range of biochemical and physiological traits including blood phenotypes (e.g., high-density lipoprotein), cardiovascular functions (e.g., pulse wave velocity) and psychological traits (e.g., neuroticism) as main groups in two population cohorts SardiNIA (~6,100 participants) and InCHIANTI (~1,400 participants). The inferred physiological age was highly correlated with chronological age (R2 > 0.8). We further defined an individual's physiological aging rate (PAR) as the ratio of the predicted physiological age to the chronological age. Notably, PAR was a significant predictor of survival, indicating an effect of aging rate on mortality. Our trait-based PAR was correlated with DNA methylation-based epigenetic aging score (r = 0.6), suggesting that both scores capture a common aging process. PAR was also substantially heritable (h2~0.3), and a subsequent genome-wide association study of PAR identified significant associations with two genetic loci, one of which is implicated in telomerase activity. Our findings support PAR as a proxy for an underlying whole-body aging mechanism. PAR may thus be useful to evaluate the efficacy of treatments that target aging-related deficits and controllable epidemiological factors.

19.
Korean J Intern Med ; 36(6): 1437-1449, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34666433

RESUMO

BACKGROUND/AIMS: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. METHODS: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). RESULTS: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. CONCLUSION: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.


Assuntos
Nicotina , Tacrolimo , Animais , Apoptose , Rim/fisiologia , Nicotina/toxicidade , Ratos , Ratos Sprague-Dawley , Tacrolimo/toxicidade
20.
Aging Cell ; 20(11): e13487, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34612579

RESUMO

The association between blood-based estimates of mitochondrial DNA parameters, mitochondrial DNA copy number (mtDNA-CN) and heteroplasmy load, with skeletal muscle bioenergetic capacity was evaluated in 230 participants of the Baltimore Longitudinal Study of Aging (mean age:74.7 years, 53% women). Participants in the study sample had concurrent data on muscle oxidative capacity (τPCr ) assessed by 31 P magnetic resonance spectroscopy, and mitochondrial DNA parameters estimated from whole-genome sequencing data. In multivariable linear regression models, adjusted for age, sex, extent of phosphocreatine (PCr) depletion, autosomal sequencing coverage, white blood cell total, and differential count, as well as platelet count, mtDNA-CN and heteroplasmy load were not significantly associated with τPCr (both p > 0.05). However, in models evaluating whether the association between mtDNA-CN and τPCr varied by heteroplasmy load, there was a significant interaction between mtDNA-CN and heteroplasmy load (p = 0.037). In stratified analysis, higher mtDNA-CN was significantly associated with lower τPCr among participants with high heteroplasmy load (n = 84, ß (SE) = -0.236 (0.115), p-value = 0.044), but not in those with low heteroplasmy load (n = 146, ß (SE) = 0.046 (0.119), p-value = 0.702). Taken together, mtDNA-CN and heteroplasmy load provide information on muscle bioenergetics. Thus, mitochondrial DNA parameters may be considered proxy measures of mitochondrial function that can be used in large epidemiological studies, especially when comparing subgroups.

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