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1.
J Exp Clin Cancer Res ; 41(1): 17, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34998399

RESUMO

BACKGROUND: Dysregulation of RNA binding protein (RBP) expression has been confirmed to be causally linked with tumorigenesis. The detailed biological effect and underlying mechanisms of the RBP GRSF1 in hepatocellular carcinoma (HCC) remain unclear. METHODS: HCC cells with stable knockdown of GRSF1 were established using two sh-RNA-encoding lentiviruses. The functions of GRSF1 in HCC were explored using MTT, colony formation, flow cytometry, and Transwell assays and a xenograft model. Transcriptomic sequencing in GRSF1-deficient MHCC-97H cells was carried out to identify the downstream effector of GRSF1. The regulatory mechanisms among GRSF1, YY1 and miR-30e-5p were investigated via RNA immunoprecipitation, luciferase, RNA pull-down and ChIP assays. Several in vivo assays were used to assess the selectivity of the small-molecule compound VE-821 in HCC and to confirm the absence of general toxicity in animal models. RESULTS: GRSF1 was frequently increased in HCC tissue and cells and was associated with worse clinical outcomes. GRSF1 functions as a novel oncogenic RBP by enhancing YY1 mRNA stability, and the GUUU motifs within the YY1 3`UTR 2663-2847 were the specific binding motifs for GRSF1. YY1 feedback promoted GRSF1 expression by binding to the GRSF1 promoter. In addition, YY1 was a critical target of miR-30e-5p, which was confirmed in this study to inhibit HCC hepatocarcinogenesis. GRSF1 and miR-30e-5p competitively regulated YY1 by binding to its 3`UTR 2663-2847 region. Finally, we identified that VE-821 blocked HCC progression by inhibiting the GRSF1/YY1 pathway. CONCLUSION: This study revealed the interaction network among GRSF1, YY1 and miR-30e-5p, providing new insight into HCC pathogenesis, and indicated that VE821 may serve as a novel agent with potential for HCC treatment through inhibition of the GRSF1/YY1 axis.

2.
Dis Markers ; 2022: 7878602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35059045

RESUMO

Objective: To clarify the protective effect of simvastatin on myocardial ischemia reperfusion injury (MIRI) and the underlying mechanism. Materials and Methods: The MIRI model in rats was firstly constructed. Twenty-four male rats were randomly assigned into the sham group, ischemia-reperfusion (I/R) group, and simvastatin group, with 8 rats in each group. Contents of superoxide dismutase (SOD) and malondialdehyde (MDA), as well as serum levels of CK and inflammatory factors, in rats were determined by the enzyme-linked immunosorbent assay (ELISA). Lactate dehydrogenase (LDH) activity in the three groups was examined. Through flow cytometry and Cell Counting Kit-8 (CCK-8) assay, apoptosis and viability in each group were detected, respectively. Relative levels of HMGB1, Kruppel-like factor 2 (KLF2), eNOS, and thrombomodulin (TM) were finally determined. Results: Simvastatin treatment markedly enhanced SOD activity and reduced contents of MDA, LDH, and creatine kinase (CK) in MIRI rats. The increased apoptosis and decreased viability following MIRI were partially reversed by simvastatin treatment. Besides, MIRI resulted in the upregulation of inflammatory factors and chemokines. Their elevations were abolished by simvastatin. In MIRI rats, simvastatin upregulated KLF2 and p-eNOS. Conclusions: Simvastatin protects inflammatory response at post-MIRI through upregulating KLF2, thus improving cardiac function.

3.
J Med Chem ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35041407

RESUMO

Studies have shown that circRNAs are important regulatory molecules involved in cell physiology and pathology. Herein, we analyzed the role of circ_ZNF512 in cardiomyocyte autophagy of myocardial ischemia/reperfusion (I/R) injury. A mouse model was induced by ligation of the left anterior descending artery followed by reperfusion. An in vitro model was also developed in cultured cardiomyocytes following hypoxia/reoxygenation (H/R) injury. It was established that EGR1 expression was increased in myocardial tissues of I/R mice and H/R-induced cardiomyocytes. Silencing of circ_ZNF512 attenuated its binding to miR-181d-5p, which in turn impaired the EGR1 expression by targeting its 3'-UTR, thus promoting the autophagy of cardiomyocytes and suppressing cell apoptosis to alleviate myocardial tissue injury. Additionally, the circ_ZNF512/miR-181d-5p/EGR1 crosstalk activated the mTORC1/TFEB signaling pathway, increasing mTORC1 expression while suppressing TFEB expression. Together, circ_ZNF512 knockdown protects against myocardial I/R injury, which may be a potential therapeutic approach for preventing myocardial I/R injury.

4.
Thyroid ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35044245

RESUMO

BACKGROUND: The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the 'X-zone' layer via unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans. METHODS: To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human non-autoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyroid-stimulating hormone (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche. RESULTS: We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid females. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and premature adrenarche. CONCLUSIONS: Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.

5.
Fish Shellfish Immunol ; 121: 223-231, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34986398

RESUMO

Calcium/calmodulin-dependent protein kinase II is a downstream mediator of calcium signalling and participates in the regulation of various cellular physiological functions. In previous studies, the expression of Eriocheir sinensis CaMKII (EsCaMKII) was significantly decreased in the thoracic ganglion after Spiroplasma eriocheiris infection, as shown using TMT-based quantitative proteomic analysis; however, the specific functions of EsCaMKII are still unclear. In this study, the full-length cDNA of EsCaMKII was 3314 bp long, consisting of a 1605 bp open reading frame encoding a protein of 535 amino acids, including a 258 aa serine/threonine protein kinase catalytic domain (EsCaMKII-CD). EsCaMKII is highly transcribed in haemocytes, nerves (thoracic ganglion), gills, and muscles, but lowly transcribed in the hepatopancreas, heart, and intestines. The transcription levels of EsCaMKII were altered in E. sinensis haemocytes after S. eriocheiris infection. After the over-expression of EsCaMKII-CD in RAW264.7 cells, the apoptosis rate of RAW264.7 cells was significantly increased. After the over-expression of EsCaMKII-CD, the morphology of RAW264.7 cells became worse after being infected with S. eriocheiris. Meanwhile, the copy number of S. eriocheiris in RAW264.7 cells was significantly decreased. From 48 h to 96 h after EsCaMKII RNA interference, the transcription levels of EsCaMKII decreased significantly. The transcription of apoptosis genes and cell apoptosis were also inhibited in haemocytes after EsCaMKII RNAi. The knockdown of EsCaMKII by RNAi resulted in significant increases in the copy number of S. eriocheiris and in the mortality of crabs during S. eriocheiris infection. These results indicate that EsCaMKII could promote the apoptosis of E. sinensis and enhance its ability to resist S. eriocheiris infection.

6.
Pharmaceutics ; 14(1)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35057070

RESUMO

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PLpro), and 3C-like protease (3CLpro) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.

7.
Hum Brain Mapp ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34984762

RESUMO

Visual attention span (VAS), which refers to the window size of multielement parallel processing in a short time, plays an important role in higher-level cognition (e.g., reading) as required by encoding large amounts of information input. However, it is still a matter of debate about the underlying neural mechanism of VAS. In the present study, a modified visual 1-back task was designed by using nonverbal stimuli and nonverbal responses, in which possible influences of target presence and position were considered to identify more pure VAS processing. A task-driven functional magnetic resonance imaging (fMRI) experiment was then performed, and 30 healthy adults participated in this study. Results of confirmatory and exploratory analyses consistently revealed that both dorsal attention network (DAN) and ventral attention network (VAN) were significantly activated during this visual simultaneous processing. In particular, more significant activation in the left superior parietal lobule (LSPL), as compared to that in the bilateral inferior frontal gyrus (IFGs), suggested a greater involvement of DAN in VAS-related processing in contrast to VAN. In addition, it was also found that the activation in temporoparietal junctions (TPJs) were suppressed during multielement processing only in the target-absent condition. The current results suggested the recruitment of LSPL in covert attentional shifts and top-down control of VAS resources distribution during the rapid visual simultaneous processing, as well as the involvement of bilateral IFGs (especially RIFG) in both VAS processing and inhibitory control. The present findings might bring some enlightenments for diagnosis of the atypicality of attentional disorders and reading difficulties.

8.
Polymers (Basel) ; 14(2)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35054646

RESUMO

Through the use of organic/inorganic hybrid dispersants-which are composed of polymeric dispersant and two-dimension nanomaterial graphene oxide (GO)-copper nanoparticles (CuNPs) were found to exhibit nano stability, air-stable characteristics, as well as long-term conductive stability. The polymeric dispersant consists of branched poly(oxyethylene)-segmented esters of trimellitic anhydride adduct (polyethylene glycol-trimethylolpropane-trimellitic anhydride, designated as PTT). PTT acts as a stabilizer for CuNPs, which are synthesized via in situ polymerization and redox reaction of the precursor Cu(CH3COO)2 within an aqueous system, and use graphene oxide to avoid the reduction reaction of CuNPs. The results show that after 30 days of storage the CuNPs/PTT/GO composite film maintains a highly conductive network (9.06 × 10-1 Ω/sq). These results indicate that organic/inorganic PTT/GO hybrid dispersants can effectively maintain the conductivity stability of CuNPs and address the problem of CuNP oxidation. Finally, the new CuNPs/PTT/GO composite film was applied to the electrocardiogram (ECG) smart clothes. This way, a stable and antioxidant-sensing electrode can be produced, which is expected to serve as a long-term ECG monitoring device.

9.
Int Immunopharmacol ; 103: 108487, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34959187

RESUMO

Synthetized from a natural oil of Houttuynia cordata, sodium houttuynia was reported to have anti-inflammatory effects. The present study aimed to investigate whether sodium houttuynia could alleviate the characteristic airway inflammation and Treg/Th17 cell imbalance of asthma in vivo. Experimental mice with neutrophilic asthma were injected with sodium houttuynia or dexamethasone (alone or in combination) intraperitoneally. The airway reactivity was measured, and bronchoalveolar lavage fluid was collected for cell count. Hematoxylin/eosin and periodic acid-Schiff staining were performed to assess pulmonary inflammation and mucus hypersecretion. Immunohistochemical analysis was conducted to determine the expression of IL-10, IL-17A, FoxP3, and RORγT in the lung tissue, and the serum levels of IL-10 and IL-17A were analyzed by ELISA. The proportion of CD4+CD25+FoxP3+ Treg and Th17 cells within the CD4+ T cell subset of splenocytes was analyzed by flow cytometry. FoxP3 and RORγT mRNA and protein expressions in the lung were analyzed by real-time PCR and western blot, respectively. Overall, sodium houttuynia was found to ameliorate the Treg/Th17 cell imbalance and reduce the airway inflammation, hyperresponsiveness, and mucus hypersecretion by increasing the frequency of CD4+CD25+FoxP3+ Treg cells and the secretion of IL-10, while decreasing the proportion of Th17 cells and IL-17A production. Although the regulatory effect of sodium houttuynia was not as good as that achieved with dexamethasone, combination of the two compounds showed improved inhibitory effects on airway hyperresponsiveness, inflammation, and mucus hypersecretion. Hence, sodium houttuynia may be beneficial for the treatment of asthma.

10.
Lab Chip ; 22(2): 367-376, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-34918732

RESUMO

Rapid, efficient, and selective separation of tumor cells from complex body fluids is urgently needed for clinical application of tumor-cell-based liquid biopsy. Herein, a size-selective affinity filtration system, named selective, user-friendly, highly porous, efficient, and rapid filter (SUPER Filter), was developed for high-performance tumor cell isolation and analysis. SUPER Filter enabled selective interaction of tumor cells with size-optimized and antibody-coated micropore walls during filtration, achieving a high efficiency of 91.0 ± 6.1% in buffer and 83.7 ± 6.4% in whole blood. Meanwhile, its larger micropore size than those of traditional filtration devices greatly reduced the nonspecific capture of background cells (55-126 cells per mL blood) with enrichment factors of 1.1 × 104-1.0 × 105 and a purity of 52.7 ± 4.2%. Moreover, its high porosity enabled ultra-fast (<5 s for 1 mL of blood or 10 mL of buffer samples) and user-friendly gravity-driven filtration. Finally, SUPER Filter demonstrated rapid, efficient, and selective separation of tumor cells from blood and large-volume pleural and ascetic fluid samples from cancer patients for morphological and molecular analysis. We expect that this size-selective affinity filtration strategy facilitates the clinical application of tumor-cell-based liquid biopsy.

11.
Nanoscale ; 14(2): 419-427, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34937077

RESUMO

Nanofibre membranes with a small diameter and a large specific surface area are widely used in the filtration field due to their small pore size and high porosity. To date, aramid nanofibres (ANFs) have received extensive research interest because of their high stiffness and excellent temperature resistance. However, the preparation of ANFs usually takes a long time, which greatly hampers the practical application of these fibres. Herein, we report the preparation of ANFs by a modified deprotonation method at elevated temperature. Owing to the increase of temperature, the preparation cycle of ANFs was shortened to 8 hours. The resulting ANF dispersion was further coated on a polypropylene melt-blown nonwoven to form a composite nonwoven filter. With the submicron porous structure, the filtration efficiency, pressure drop and quality factor of the filter were 95.61%, 38.22 Pa and 0.082 Pa-1, respectively. Compared to the pristine nonwoven, the filtration, mechanical, and heat insulation properties of the composite filter were also significantly improved. This work may offer a simple and efficient way for enhancing the air filtration performances of current filters.

12.
Bioresour Technol ; 344(Pt A): 126163, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34688859

RESUMO

Metal-organic frameworks (MOFs) could serve as efficient matrixes to immobilize cellulase because of their high stability and porous morphology. Herein, the Zr-based MOFs (UiO-66 and UiO-66-NH2) assisted 20 wt% high-solids hydrolysis of untreated corncob residues (CRs) at low enzyme loading was investigated. Glucan hydrolysis yields increased to 60.55% and 71.47% by separately adding 4 g/L UiO-66 and UiO-66-NH2 at 5 FPU/g-glucan cellulase dosage. The maximum hydrolysis yield reached 90.01% at 10 FPU/g-glucan in the presence of 4 g/L UiO-66-NH2. Analysis of free protein concentration and cellulase activity suggested that MOFs effectively increased cellulase catalytic activity and stability, thus boosted CRs enzymatic hydrolysis efficiency. Additionally, UiO-66-NH2 immobilization gave a high catalytic activity because of the abundant anchor sites of NH2 groups. This research presents the promising future of MOFs' application in lignocellulosic biomass bioconversion and other areas requiring immobilized enzymes.


Assuntos
Celulase , Estruturas Metalorgânicas , Hidrólise , Compostos Organometálicos , Ácidos Ftálicos , Zea mays
13.
J Colloid Interface Sci ; 607(Pt 2): 1457-1465, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34598027

RESUMO

Lithium iron phosphate (LFP) is one of the promising cathode materials of lithium ion battery (LIB), but poor electrical conductivity restricts its electrochemical performance. Carbon coating can improve electrical conductivity of LFP without changing its intrinsic property. Uniform coating of carbon on LFP is significant to avoid charge congregation and unpreferable redox reactions. It is the first time to apply the commercial organic binder, Super P® (SP), as carbon source to achieve uniform coating on LFP as cathode material of LIB. The simple and economical mechanofusion method is firstly applied to coat different amounts of SP on LFP. The LIB with the cathode material of optimized SP-coated LFP shows the highest capacity of 165.6 mAh/g at 0.1C and 59.8 mAh/g at 10C, indicating its high capacity and excellent high-rate charge/discharge capability. SP is applied on other commercial LFP materials, M121 and M23, for carbon coating. Enhanced high-rate charge/discharge capabilities are also achieved for LIB with SP-coated M121 and M23 as cathode materials. This new material and technique for carbon coating is verified to be applicable on different LFP materials. This novel carbon coating method is expected to apply on other cathode materials of LIB with outstanding electrochemical performances.

14.
BMJ Open ; 11(12): e048269, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876418

RESUMO

OBJECTIVE: To investigate the reliability and validity of Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) for different population cohorts in the city of Guangzhou, Guangdong, China and to provide evidence and tools for further evaluation of healthy fitness of Chinese population and related factors. DESIGN: Cross-sectional study. SETTING: Urban neighbourhood and Medical University. PARTICIPANTS: Elderly people (n=393; mean age 68.27±6.38 years; 53.18% male), university students (n=390; mean age 19.29±1.29 years; 38.21% male) and urban residents (n=393; mean age 32.23±9.41 years; 44.78% male). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were evaluated the reliability and validity of HFMS V1.0 by internal consistency evaluation, split-half reliability, test-retest reliability, convergent and discriminant construct validity, and factor analysis. RESULTS: The Cronbach's α coefficients for HFMS V1.0 were all greater than 0.85 for overall scale of total samples and three individual groups, and the split-half reliability and intragroup correlation coefficients were both greater than 0.70 (p<0.01). The correlation of each item, dimension and subscales ranged from 0.52 to 0.91 (p < 0.01). A total of 10 factors were screened by exploratory factor analysis with the cumulative contribution rate of 61.40%, basically consistent with the theoretical structure of scale. The confirmatory factor analysis indicated good fit: CMIN/DF=3.45, root mean square error of approximation=0.05, GFI=0.91, AGFI=0.90, IFI=0.90, comparative fit index=0.90. CONCLUSION: HFMS V1.0 showed acceptable reliability and validity in the test of healthy fitness of general population in Guangzhou. This scale could be a reliable measurement tool for evaluation of healthy fitness and potential risk factors.

15.
Cancers (Basel) ; 13(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34885073

RESUMO

Conventional treatment of dedifferentiated endometrial carcinoma (DEC)-an uncommon and highly aggressive uterine malignancy-is beset by high failure rates. A line of research that holds promise to overcome these limitations is tailored treatments targeted on specific molecular alterations. However, suitable preclinical platforms to allow a reliable implementation of this approach are still lacking. Here, we developed a patient-derived xenograft (PDX) model for preclinical testing of investigational drugs informed by molecular data. The model-termed PDX-mLung was established in mice implanted with lung metastatic lesions obtained from a patient with DEC. Histologic and whole-exome genetic analyses revealed a high degree of identity between PDX-mLung and the patient's parental lesions (both primary DEC and lung metastases). Interestingly, molecular analyses revealed that PDX-mLung harbored druggable alterations including a FGFR2 mutation and CCNE2 amplification. Targeted combined treatment with the FGFR inhibitor lenvatinib and the cell cycle inhibitor palbociclib was found to exert synergistic therapeutic effects against in vivo tumor growth. Based on the results of RNA sequencing, lenvatinib and palbociclib were found to exert anti-tumor effects by interfering interferon signaling and activating hormonal pathways, respectively. Collectively, these data provide proof-of-concept evidence on the value of PDX models for preclinical testing of molecularly informed drug therapy in difficult-to-treat human malignancies. Further clinical research is needed to examine more rigorously the potential usefulness of the lenvatinib and palbociclib combination in patients with DEC.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34852196

RESUMO

Perovskite oxides have emerged as promising candidates for the oxygen evolution reaction (OER) electrocatalyst due to their flexible lattice structure, tunable electronic structure, superior stability, and cost-effectiveness. Recent research studies have mostly focused on the traditional methods to tune the OER performance, such as cation/anion doping, A-/B-site ordering, epitaxial strain, oxygen vacancy, and so forth, leading to reasonable yet still limited activity enhancement. Here, we report a novel strategy for promoting the OER activity for perovskite LaNiO3 by crystal phase engineering, which is realized by breaking long-range chemical bonding through amorphization. We provide the first and direct evidence that perovskite oxides with an amorphous structure can induce the self-adaptive process, which helps enhance the OER performance. This is evidenced by the fact that an amorphous LaNiO3 film on glassy carbon shows a 9-fold increase in the current density compared to that of an epitaxial LaNiO3 single crystalline film. The obtained current density of 1038 µΑ cm-2 (@ 1.6 vs RHE) is the largest value among the literature reported values. Our work thus offers a new protocol to boost the OER performance for perovskite oxides for future clean energy applications.

17.
J Cell Mol Med ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34894202

RESUMO

Stress is one of the leading causes of male infertility, but its exact function in testosterone synthesis has scarcely been reported. We found that adult male rats show a decrease in bodyweight, genital index and serum testosterone level after continual chronic stress for 21 days. Two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-MS analysis identified 10 differentially expressed proteins in stressed rats compared with controls. A strong protein interaction network was found to be centred on Atp5a1 among these proteins. Atp5a1 expression significantly decreased in Leydig cells after chronic stress. Transfection of Atp5a1 siRNAs decreased StAR, CYP11A1, and 17ß-HSD expression by damaging the structure of mitochondria in TM3 cells. This study confirmed that chronic stress plays an important role in testosterone synthesis by regulating Atp5a1 expression in Leydig cells.

18.
J Biomed Sci ; 28(1): 85, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34886870

RESUMO

Parkinson's disease (PD), or paralysis agitans, is a common neurodegenerative disease characterized by dopaminergic deprivation in the basal ganglia because of neuronal loss in the substantia nigra pars compacta. Clinically, PD apparently involves both hypokinetic (e.g. akinetic rigidity) and hyperkinetic (e.g. tremor/propulsion) symptoms. The symptomatic pathogenesis, however, has remained elusive. The recent success of deep brain stimulation (DBS) therapy applied to the subthalamic nucleus (STN) or the globus pallidus pars internus indicates that there are essential electrophysiological abnormalities in PD. Consistently, dopamine-deprived STN shows excessive burst discharges. This proves to be a central pathophysiological element causally linked to the locomotor deficits in PD, as maneuvers (such as DBS of different polarities) decreasing and increasing STN burst discharges would decrease and increase the locomotor deficits, respectively. STN bursts are not so autonomous but show a "relay" feature, requiring glutamatergic synaptic inputs from the motor cortex (MC) to develop. In PD, there is an increase in overall MC activities and the corticosubthalamic input is enhanced and contributory to excessive burst discharges in STN. The increase in MC activities may be relevant to the enhanced beta power in local field potentials (LFP) as well as the deranged motor programming at the cortical level in PD. Moreover, MC could not only drive erroneous STN bursts, but also be driven by STN discharges at specific LFP frequencies (~ 4 to 6 Hz) to produce coherent tremulous muscle contractions. In essence, PD may be viewed as a disorder with deranged rhythms in the cortico-subcortical re-entrant loops, manifestly including STN, the major component of the oscillating core, and MC, the origin of the final common descending motor pathways. The configurations of the deranged rhythms may play a determinant role in the symptomatic pathogenesis of PD, and provide insight into the mechanism underlying normal motor control. Therapeutic brain stimulation for PD and relevant disorders should be adaptively exercised with in-depth pathophysiological considerations for each individual patient, and aim at a final normalization of cortical discharge patterns for the best ameliorating effect on the locomotor and even non-motor symptoms.

19.
J Vis Exp ; (178)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34958080

RESUMO

Cellular heterogeneity poses challenges to understanding the function of complex tissues at a transcriptome level. Using cell-type-specific RNAs avoids potential pitfalls caused by the heterogeneity of tissues and unleashes the powerful transcriptome analysis. The protocol described here demonstrates how to use the Translating Ribosome Affinity Purification (TRAP) method to isolate ribosome-bound RNAs from a small amount of EGFP-expressing cells in a complex tissue without cell sorting. This protocol is suitable for isolating cell-type-specific RNAs using the recently available NuTRAP mouse model and could also be used to isolate RNAs from any EGFP-expressing cells.

20.
Gastroenterol Rep (Oxf) ; 9(6): 489-504, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34925847

RESUMO

Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract, posing a significant risk to human health. Over the past 10 years, the pathological characteristics and the prognosis of GC have been determined based on the locations of the tumors that were then classified into two types-proximal and distal GC. This review focuses on the differences in epidemiology, etiology, cell source, pathological characteristics, gene expression, molecular markers, manifestations, treatment, prognosis, and prevention between proximal and distal GC to provide guidance and a basis for clinical diagnosis and treatment.

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