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1.
Neurobiol Aging ; 115: 70-76, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35489321

RESUMO

Presenilin 1 (PSEN1) mutations are a major cause of familial Alzheimer's disease. The pathogenic variant, PSEN1 p.G417S, has been reported to be associated with spastic paraparesis and cotton wool plaques in Japan. Here, we report a 3 generation Chinese pedigree that included 10 patients presenting with early-onset and rapid progression of parkinsonism with cognitive impairment in their third or fourth decade of life. Three additional living patients developed different degrees of cognitive impairment, without movement disorders. Magnetic resonance imaging of the brain showed white matter hyperintensities, multiple microbleeds, and enlarged perivascular spaces. Whole exome sequencing analysis of the proband detected the mutation, p.G417S, in PSEN1, which was completely co-segregated with the disease phenotype within the family by Sanger sequencing. 3D protein structures predicted that the mutation might influence contact with the lipid membrane and the interaction with beta-catenin. Our study provides insights into the heterogeneity in clinical presentation and imaging associated with mutations in PSEN1.

2.
Mol Ther ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35450820

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy has faced a series of challenges and has shown very little efficacy in solid tumors to date. Although genetically engineered macrophages have achieved definite therapeutic effect in solid tumors, heterogeneous expression of engineered proteins and the potential for toxicity limit further applications. Herein, we propose a nongenetic and simple macrophage cell engineering strategy through glycan metabolic labeling and click reaction for the treatment of solid tumors. The aptamer-engineered M1 macrophage (ApEn-M1) showed enhanced active targeting ability for tumor cells in vitro and in vivo, resulting in significant cytotoxicity effects. Moreover, ApEn-M1 exhibited superior antitumor efficacy in a breast cancer xenograft mouse model and a lung metastasis mouse model of breast cancer. Interestingly, the ApEn-M1 could reprogram the immunity microenvironment by increasing T cell infiltration and enhancing T cell activity in the tumor region. Additionally, the administration of ApEn-M1 showed no obvious systemic side effects. With glycan metabolic labeling, the macrophages could be efficiently labeled with aptamers on the cell surface via click reaction without genetic alteration or cell damage. Hence, this study serves as a proof of concept for cell-surface anchor engineering and expands the range of nongenetic macrophage cell engineering strategies.

3.
Clin Oral Investig ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35399138

RESUMO

OBJECTIVE: To assess the radiographic outcomes and prognostic factors in nonvital immature permanent teeth after apexification with modified calcium hydroxide paste. MATERIALS AND METHODS: Clinical and radiographic data were collected from 115 necrotic immature permanent teeth (71 caused by trauma and 44 caused by dens evaginatus) treated with apexification using a modified calcium hydroxide. Postoperative root morphology and changes in radiographic root area (RRA) on periapical radiographs were determined and statistically evaluated. Regression analysis was performed to identify factors associated with the outcomes of apexification. RESULTS: The average time for a calcified barrier formation was 10.66 ± 6.37 months. The root morphology after apexification with calcium hydroxide + iodoform paste was similar to that previously described after calcium hydroxide apexification. Compared with the trauma cases, the dens evaginatus cases revealed more type I (40.91% vs 16.9%) and less type II morphology (45.45% vs 67.61%). Although the changes in RRA were limited, the dens evaginatus cases showed greater increment of RRA than the trauma cases (4.12% ± 5.58% vs 0.70% ± 5.21%, P < 0.001). A significant association was found between the preoperative stage of root development and postoperative percentage change in RRA (P < 0.001). CONCLUSIONS: Teeth caused by dens evaginatus had better outcomes after apexification than teeth caused by trauma. Early stages of root development were associated with superior radiographic outcomes. CLINICAL RELEVANCE: Apexification provided reliable outcomes in the treatment of immature teeth with pulp necrosis and apical periodontitis, even though the root development is limited. Treatment decision should be made with comprehensive evaluation of prognostic factors.

4.
Front Neurosci ; 16: 846095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464305

RESUMO

Increasing evidence reveals sex as an important factor in the development of Parkinson's disease (PD), but associations between genes on the sex chromosomes and PD remain unknown. TAF1 is a gene located on the X chromosome which is known to cause X-linked syndromic mental retardation-33 (MRXS33) and X-linked Dystonia-Parkinsonism (XDP). In this study, we conducted whole-exome sequencing (WES) among 1,917 patients with early-onset or familial PD and 1,652 controls in a Chinese population. We detected a hemizygous frameshift variant c.29_53dupGGA(CAG)2CTACCATCA(CTG)2C (p.A19Dfs*50) in two unrelated male patients. Further segregation analysis showed an unaffected family member carried this variant, which suggested the penetrance of the variant may be age-related and incomplete. To verify the effects of TAF1 on PD, genetic analyses were carried separately by gender. Analysis of rare variants by optimal sequence kernel association (SKAT-O) test showed a nominally significant difference in variant burden between the male PD patients and controls (2.01 vs. 1.38%, p = 0.027). In the female group, none of the variant types showed significant association with PD in this study. In conclusion, we found rare variants in TAF1 may be implicated in PD, but further genetic and functional analyses were needed.

5.
Front Oncol ; 12: 848206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359417

RESUMO

Breast cancer (BCa) is the most common malignancy in women and claudin-low breast cancer (CL-BCa) is a newly identified BCa subtype characterized by low expression of claudin 3&4&7. However, the hub genes associated with the recruitment of immune cells into CL-BCa were rarely described. This study aimed at exploring the differentially expressed hub genes associated with tumor-infiltrating immune cells in CL-BCa by a multi-approach bioinformatics analysis. The top 200 genes associated with CL-BCa were screened in the METABRIC dataset; the PPI network was constructed using STRING and Cytoscape; tumor-infiltrating immune cells were analyzed by TIMER 2.0; and the correlation of feature cytokines and claudins on survival was examined in METABRIC and TCGA datasets. Consequently, we found that the fraction of tumor-infiltrating immune cells, especially CD8+T cells and macrophages, increased in the CL-BCa. Differentially expressed cytokines (CCL5, CCL19, CXCL9 and CXCL10) and claudins (CLDN8, CLDN11 and CLDN19) were related to the overall survival, and their expression levels were also examined both in tumor tissues of CL-BCa patients by IHC and in typical CL-BCa cell lines by qPCR. Finally, the BCa patients with high expression of these DEGs (CCL5, CCL19, CXCL9, CLDN8 and CLDN11) showed a better overall survival. This study sheds light on molecular features of CL-BCa on immune microenvironments and contributes to identification of prognosis biomarkers for the CL-BCa patients.

6.
Front Pharmacol ; 13: 845018, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401174

RESUMO

Oxytocin (OT) and its receptor are promising targets for the treatment and prevention of the neuropathic pain. In the present study, we compared the effects of a single and continuous intrathecal infusion of OT on nerve injury-induced neuropathic pain behaviours in mice and further explore the mechanisms underlying their analgesic properties. We found that three days of continuous intrathecal OT infusion alleviated subsequent pain behaviours for 14 days, whereas a single OT injection induced a transient analgesia for 30 min, suggesting that only continuous intrathecal OT attenuated the establishment and development of neuropathic pain behaviours. Supporting this behavioural finding, continuous intrathecal infusion, but not short-term incubation of OT, reversed the nerve injury-induced depolarizing shift in Cl- reversal potential via restoring the function and expression of spinal K+-Cl- cotransporter 2 (KCC2), which may be caused by OT-induced enhancement of GABA inhibitory transmission. This result suggests that only continuous use of OT may reverse the pathological changes caused by nerve injury, thereby mechanistically blocking the establishment and development of pain. These findings provide novel evidence relevant for advancing understanding of the effects of continuous OT administration on the pathophysiology of pain.

7.
Chemosphere ; 298: 134196, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35276103

RESUMO

The important role of microbes in the biomineralization and migration behavior of uranium in the field of environmental chemistry has been well emphasized in previous work. However, limited work on mineralization processes of indigenous microorganism has prevented us from a deeper understanding of the process and mechanisms of uranium biomineralization. In this work, the dynamic process and mechanism of uranium biomineralization in Enterobacter sp. X57, a novel uranium-tolerant microorganism separated from uranium contaminated soil, were systematically investigated. Enterobacter sp. X57 can induce intracellular mineralization of U (VI) to Uramphite (NH4UO2PO4·3H2O) under neutral conditions by alkaline phosphatase. In this biomineralization process, soluble U (VI) first bonded with the amino and phosphate groups on the plasma membrane, providing initial nucleation site for the formation of U (VI) biominerals. Then the impairment of cell barrier function and the enhancement of alkaline phosphatase metabolism occurred with the accumulation of uranium in cells, creating a possible pathway for soluble U (VI) to diffuse into the cell and be further mineralized into U (VI)-phosphate minerals. All the results revealed that the intracellular biomineralization of uranium by Enterobacter sp. X57 was a combined result of biosorption, intracellular accumulation and phosphatase metabolism. These findings may contribute to a better understanding of uranium biomineralization behavior and mechanism of microorganisms, as well as possible in-situ bioremediation strategies for uranium by indigenous microorganisms.


Assuntos
Urânio , Fosfatase Alcalina/metabolismo , Biodegradação Ambiental , Biomineralização , Enterobacter/metabolismo , Fosfatos/metabolismo , Urânio/química
9.
Plant Dis ; 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35350888

RESUMO

Juglans regia L. is one of the major cultivated walnut species in China for nuts and wood (Pollegioni et al. 2012). In June 2020, branches with blight symptoms were observed in an orchard at Chongzhou City (30°33'34″N, 103°38'35″E). In an orchard of 30 hectares, disease incidence was around 50%. A total of 15 plants were sampled and 40% of their branches were affected by this disease. Firstly, brown and irregular spots appeared, then the spots gradually expanded and encircled the branch, which eventually killed the branch. Five samples of diseased branches from different trees were collected and a single fungal isolate was obtained from each of the five samples using the single ascospore isolation (Chomnunti et al. 2014). Colonies of the five isolates on potato dextrose agar (PDA) were identical that initially appeared white on the top, becoming light to dark brown with age. On the host, ascostroma were black, globose to subglobose, short-papillate, ostiolate, 260 - 410 × 210 - 320 µm (x = 335 × 265 µm, n = 20). Asci were 8-spored, bitunicate, cylindrical, short pedicellate, 55 - 78 × 8 - 12 µm (x = 67.5 × 10 µm, n = 40). Ascospores were 1-septate, fusiform to ellipsoidal, slightly curved, guttulate, 12 - 17 × 3 - 5 µm (x = 14.5 × 4 µm, n = 40). These sexual morphological characteristics are consistent with the Palmiascoma qujingense Phook. & K.D. Hyde (Monkai et al. 2021). Asexual morphs were formed on PDA in incubator after 17 days (25℃, 90% relative humidity, 12-h photoperiod). Conidiomata were black, globose to subglobose, 220 - 300 × 240 - 380 µm (x = 270 × 310 µm, n = 20). Conidia were oblong to ellipsoidal, aseptate and smooth-walled, 3 - 7 × 2 - 4 µm (x = 4.9 × 3 µm, n = 50). The genomic DNA of a representative isolate SICAUCC 21-0013 was extracted, and the internal transcribed spacers (ITS) region, large subunit rDNA (LSU) region, small subunit rDNA (SSU) region, and the largest subunit of RNA polymerase II (rpb2) gene were amplified and sequenced with primers ITS5/ITS4 (White et al. 1990), LR0R/LR5 (Rehner et al. 1994), NS1/NS4 (White et al. 1990), and fRPB2-5F/fRPB2-7cR (Liu et al. 1999), respectively. The sequences were deposited in NCBI with accession numbers MZ983549, MZ959419, MZ951112, and MZ818772, respectively, which showed 100%, 100%, 99.14%, and 99.59% identities with P. qujingense KUMCC 19-0201 (holotype) (accession numbers MT477185, MT477186, MT477183, MT495782respectively). Phylogenetic analysis (maximum likelihood) based on a concatenated dataset showed 93% bootstrap support values with P. qujingense. To verify Koch's postulates, 9 healthy branches from three 1-year-old seedlings were inoculated with conidial suspension (106 conidia/ml) from 4-week-old cultures via pin-prick inoculation (Desai et al. 2019), and the same number of seedlings and branches were inoculated with sterile water as controls. Plants were placed in a greenhouse at 25℃ and 90% RH on a 12-h fluorescent light/dark regime. After 28 days, brown spots were formed on P. qujingense-inoculated branches and similar to those observed in the field, while the controls remained asymptomatic. The pathogen was re-isolated from the lesions and identified by morphology and phylogeny. To our knowledge, this is the first report of P. qujingense causing branch blight on J. regia in the world. This disease potentially impacts the growth and yield of J. regia, and control measures should be made.

10.
Front Pharmacol ; 13: 807498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281887

RESUMO

Chemotherapy, as one of the principal modalities for cancer therapy, is limited by its non-specific and inefficient delivery to tumors. To overcome these limitations, we report herein a dual-targeted aptamer-decorated DNA hydrogel system (DTA-H) to achieve efficient, stable, and targeted delivery of drugs. Firstly, DNA hydrogel was formed by the rolling circle amplification. By reasonable design, double target and multivalent aptamers were decorated on DNA hydrogel to load DOX. The results confirmed that DTA-H can deliver chemotherapy drugs and aptamer nucleic acids drugs to target cells, inducing degradation of HER2 protein while chemotherapy is synergistic to inhibit HER2-positive breast cancer growth. The proposed drug delivery system has significant potential to achieve efficient, stable, and targeted delivery of drugs and cancer therapy.

11.
Parkinsonism Relat Disord ; 97: 8-14, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35276586

RESUMO

INTRODUCTION: Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative diseases in the elderly. Recently, some variants of AD-causal genes (APP, PSEN1, PSEN2) have been reported in PD. In this study, we investigated the association between coding variants of AD-causal genes and PD in a large Chinese population cohort. METHODS: We performed whole-exome sequencing (WES) on 1,917 patients with early-onset or familial PD and 1,652 controls, and whole-genome sequencing (WGS) on 1,962 sporadic late-onset PD and 1,279 controls. Genetic and phenotypic data were analyzed with regression analyses and the optimized sequence kernel association test. Further validation study was performed by Fisher's exact test. RESULTS: We found that rs75733498 in the PSEN2 gene was significantly associated with early-onset or familial PD; however, no significant relationship was discovered between rs75733498 and sporadic late-onset PD. The result of the validation study still revealed a significant association between rs75733498 and PD. We observed a suggestive association with APP gene in early-onset or familial PD when considering damaging missense variants alone (p = 0.018) or combined with loss-of-function variants (p = 0.029). Further phenotypic analysis did not demonstrate any significant associations. CONCLUSION: Our results support a possible genetic contribution of AD-causal genes to PD. These findings warrant further genetic and functional confirmation, and more powerful association studies will better decipher the mechanisms of PD.

12.
Antioxidants (Basel) ; 11(2)2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35204190

RESUMO

Idiopathic pulmonary fibrosis (IPF) can severely disrupt lung function, leading to fatal consequences, and there is currently a lack of specific therapeutic drugs. Bergenin is an isocoumarin compound with lots of biological functions including antioxidant activity. This study evaluated the potential beneficial effects of bergenin on pulmonary fibrosis and investigated the possible mechanisms. We found that bergenin alleviated bleomycin-induced pulmonary fibrosis by relieving oxidative stress, reducing the deposition of the extracellular matrix (ECM) and inhibiting the formation of myofibroblasts. Furthermore, we showed that bergenin could induce phosphorylation and expression of p62 and activation of Nrf2, Nrf2 was required for bergenin-induced p62 upregulation, and p62 knockdown reduced bergenin-induced Nrf2 activity. More importantly, knockdown of Nrf2 or p62 could abrogate the antioxidant activity of bergenin and the inhibition effect of bergenin on TGF-ß-induced ECM deposition and myofibroblast differentiation. Thereby, a regulatory loop is formed between p62 and Nrf2, which is an important target for bergenin aimed at treating pulmonary fibrosis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35072623

RESUMO

BACKGROUND: Thyroid cancer is the most common malignancy of the endocrine system, accounting for ~ 5% of all thyroid nodules and 1% of all systemic malignancies. BRAF mutations, primarily p.V600E hot spot mutations, are found in 60 - 70% of papillary thyroid cancer cases (PTC) and in 33 - 40% of fatal anaplastic thyroid cancers (ATC), also called poorly differentiated thyroid cancer. Dabrafenib was approved by the United States Food and Drug Administration (FDA) in 2018 to be applied in combination with trametinib for unresectable advanced or metastatic anaplastic thyroid cancer harboring the BRAFV600E mutation. Unfortunately, there are few reports on the pathophysiology, molecular mechanism, and risk factors of interstitial lung disease induced by combined BRAF- and MEK-targeted therapy. CASE PRESENTATION: We treated a 73-year-old man with metastatic BRAFV600E-mutated poorly differentiated thyroid cancer using the combination of dabrafenib and trametinib. Although a significant morphologic tumor response was observed in our patient using combined BRAF- and MEK-targeted therapy, he presented with non-febrile respiratory failure, and his chest computed tomography (CT) revealed bilateral reticulation and pleural effusion. Withdrawal from dabrafenib-trametinib and administration of methylprednisolone rapidly improved his respiratory status and imaging features. CONCLUSION: The mechanisms of lung disease after the combined treatment with dabrafenib and trametinib are unclear. We hypothesized that dual-targeted therapy with a BRAF inhibitor, dabrafenib, and a MEK inhibitor, trametinib, might prevent the regeneration and proliferation of fibrotic epithelium in lung disease by blocking downstream proliferative signals.

14.
Phytopathology ; 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35050680

RESUMO

Soybean cyst nematode (Heterodera glycines Ichinohe, SCN), one of the most devastating soybean pathogens, causes a significant yield loss in soybean production. One of the most effective ways to manage SCN is to grow resistant cultivars. Therefore, comparative study using resistant and susceptible soybean cultivars provides a powerful tool to identify new genes involved in soybean SCN resistance. In present study, a transcriptome analysis was carried out using both the resistant (PI88788) and susceptible (Williams 82) soybean cultivars to characterize the responses to nematode infection. Various defense-related genes and different pathways involved in nematode resistance were recognized as being highly expressed in resistant cultivar. Promoter-GUS analysis was conducted to monitor the spatial expression pattern of the genes highly induced by nematode infection. Two nematode-inducible promoters for Glyma.05g147000 (encoding caffeoyl-CoA O-methyltransferase) and Glyma.06g036700 (encoding cupredoxin superfamily protein), were characterized and the promoters could efficiently drive the expression of known nematode resistance genes (α-SNAPRhg1HC or GmSHMT) to affect soybean SCN resistance. Interestingly, expression of the cupredoxin family genes were upregulated not only by SCN, but also by JA treatment. DNA sequence analysis identified that a conserved motif (GGTGCATG) with high similarity to SCNbox1 and GC-rich element is enriched in their promoter regions, suggesting its potential to serve as a nematode-responsive regulatory element. Overexpression of Glyma.06g036700 significantly enhanced soybean resistance to cyst nematode. Overall, our findings not only highlight the essential role of cupredoxin family genes in SCN resistance, but also offer potential functional tools to develop nematode resistance in crops.

15.
Org Lett ; 24(2): 637-641, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-34978820

RESUMO

A Ni-mediated decarboxylative silylation of alkynyl cyclic carbonates used as versatile propargylic surrogates is reported affording a wide range of highly substituted 2,3- and 3,4-allenol products in good yields. The formal cross-coupling between a tentative intermediate Ni(allenyl) and the silyl reagent was further extended to enantiospecific conversions providing access to chiral allene synthons. This protocol marks the first Ni-catalyzed propargylic silylation proceeding through an SN2' manifold.

16.
Anticancer Drugs ; 33(1): e486-e490, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261918

RESUMO

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are an effective treatment for common EGFR mutations in non-small-cell lung cancer (NSCLC). Rarer EGFR mutations such as kinase domain duplications (KDDs) have been identified, but the optimal therapy following treatment resistance remains unknown. We report two patients who were diagnosed with NSCLC including KDD. For case 1, afatinib (40 mg once daily) was at first effective but then became ineffective. Consequently, osimertinib therapy (80 mg once daily) was administered. As of 26 May 2021, the osimertinib therapy achieved a stable disease state according to the chest computed tomography scan. As for case 2, the patient received second-line chemotherapy and anlotinib (12 mg once daily) for 6 months and died in May 2020. Here, we describe osimertinib as an effective therapy for EGFR-KDD positive lung adenocarcinoma and thereby provide a new alternative for further treatment following resistance to first- and second-generation EGFR-TKIs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas , Adulto , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/genética , China , Éxons , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino
17.
Neurobiol Aging ; 109: 269-272, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34531044

RESUMO

Recent studies have suggested ARSA, a gene responsible for metachromatic leukodystrophy, could be a genetic modifier of Parkinson's disease (PD) pathogenesis, acting as a molecular chaperone for α-synuclein. To elucidate the role of ARSA variants in PD, we did a comprehensive analysis of ARSA variants by performing next-generation sequencing on 477 PD families, 1440 sporadic early-onset PD patients and 1962 sporadic late-onset PD patients and 2636 controls from Chinese mainland, as well as the association between ARSA variants and cognitive function of PD patients. We identified 2 familial PD following autosomal dominant inherence carrying rare variants of ARSA, but they had limited clinical significance. We detected a total of 81 coding variants of ARSA in our subjects but none of the identified variants were associated with either susceptibility or cognitive performance of PD, while loss-of-function variants showed slightly increased burden in late-onset PD (0.25% vs. 0%, p = 0.08). Our results suggested ARSA may not play important roles in PD of Chinese population.


Assuntos
Cerebrosídeo Sulfatase/genética , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Variação Genética/genética , Resultados Negativos , Doença de Parkinson/genética , /genética , Cerebrosídeo Sulfatase/fisiologia , Feminino , Humanos , Mutação com Perda de Função/genética , Masculino , alfa-Sinucleína
18.
Carcinogenesis ; 43(2): 150-159, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-34922339

RESUMO

Breast cancer is the most common malignancy among women worldwide. Functional studies have demonstrated that miRNA dysregulation in many cases of cancer, in which miRNAs act as either oncogenes or tumor suppressor. Here we report that miR-345-3p is generally upregulated in breast cancer tissues and breast cancer cell lines. Overexpression and inhibition of miR-345-3p revealed its capacity in regulating proliferation and invasion of breast cancer cells. Further research identified protein phosphatase 2 catalytic subunit alpha (PPP2CA), a suppressor of AKT phosphorylation, as a candidate target of miR-345-3p. In vitro, miR-345-3p mimics promoted AKT phosphorylation by targeting its negative regulator, PPP2CA. Blocking miR-345-3p relieved its inhibition of PPP2CA, which attenuated PI3K-AKT signaling pathway. In vivo, inhibiting miR-345-3p by miR-345-3p-inhibition lentivirus suppressed tumor growth and invasiveness in mice. Together, the miR-345-3p/PPP2CA signaling axis exhibits tumor-promoting functions by regulating proliferation and invasion of breast cancer cells. These data provide a clue to novel therapeutic approaches for breast cancer.


Assuntos
Neoplasias da Mama , MicroRNAs , Proteína Fosfatase 2 , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética
19.
Water Res ; 208: 117839, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34801819

RESUMO

Low economic gains from biogas drive research on shifting to volatile fatty acid (VFA) production during anaerobic sludge digestion. pH control and methanogenesis inhibition are widely used strategies for VFA production via anaerobic digestion of sludge. However, these strategies require perpetual dosing of chemicals, increasing cost and operation complexity. Here, we applied electrochemical pretreatment (EPT) (12 V/30 min) for VFA production during anaerobic sludge digestion. The underlying mechanisms of the VFA production induced by EPT were explored systematically through analyses of the changes in the EPT operation parameters, the sludge characteristics, and the microbial community structure and functional enzymes involving in the subsequent sludge digestion. EPT with carbon-based electrodes selectively inhibited methanogenesis by down-regulating heterodisulfide reductase without affecting enzymatic acidogenesis and hydrolysis, resulting in accumulation of VFAs (up to 389±12 mg acetic acid equivalent/L). Propionate and acetate were, respectively enriched to 89 and 75% of the total VFAs after carbon- and graphite- EPT. Titanium-EPT produced lower levels of VFA; instead, biogas yield increased by ∼20%. We anticipate that EPT will advance VFA recovery from diverse organic wastes to meet the global challenge of resource supply and waste management.


Assuntos
Biocombustíveis , Esgotos , Anaerobiose , Reatores Biológicos , Digestão , Ácidos Graxos Voláteis , Concentração de Íons de Hidrogênio , Metano
20.
Front Aging Neurosci ; 13: 749109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867278

RESUMO

Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson's disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD. Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test. Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients. Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.

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