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1.
AIDS ; 38(6): 803-812, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578958

RESUMO

OBJECTIVES: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH. METHODS: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. RESULTS: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. CONCLUSION: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Pessoa de Meia-Idade , Idoso , Humanos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , China , Resultado do Tratamento , Contagem de Linfócito CD4 , Carga Viral
2.
Ying Yong Sheng Tai Xue Bao ; 35(1): 133-140, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38511449

RESUMO

Wetlands store one third of global soil organic carbon (SOC) and are strongly affected by artificial drainage. The impact of drainage-induced water-table decline on carbon cycling in different wetlands, particularly microbial transformation processes, remains unclear. To address this knowledge gap, we collected soil samples from two typical wetlands of China (a nutrient-poor bog located in Dajiuhu and a nutrient-rich fen in Hongyuan) and conducted an incubation experiment with the addition of 13C-labeled glucose to analyze the effects of short- and long-term drainage on SOC decomposition, extracellular enzyme activity, microbial carbon use efficiency (CUE), and microbial carbon accumulation efficiency (CAE). The results showed that both short- and long-term drainage significantly increased SOC decomposition rates in both wetlands (from 1.47 µg C·g-1·h-1 in submerged soils to 2.47 µg C·g-1·h-1 in drained soils), microbial biomass carbon derived from glucose (from 0.21 mg C·g-1 to 1.00 mg C·g-1) and CAE (from 0.29 to 0.73), but did not alter CUE (ranging from 0.34 to 0.86). Long-term drainage increased α-glucosidase activity in the Dajiuhu wetland and decreased ß-glucosidase and phenol oxidase activities in the Hongyuan wetland. In conclusion, drainage enhanced the 'microbial carbon pump' and its efficiency in wetlands mainly via increasing microbial intracellular metabolism (including respiration), but also acce-lerated SOC decomposition.


Assuntos
Solo , Áreas Alagadas , Carbono/análise , Microbiologia do Solo , China , Glucose
3.
Nat Protoc ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514838

RESUMO

The synthesis of synthetic intracellular polymers offers groundbreaking possibilities in cellular biology and medical research, allowing for novel experiments in drug delivery, bioimaging and targeted cancer therapies. These macromolecules, composed of biocompatible monomers, are pivotal in manipulating cellular functions and pathways due to their bioavailability, cytocompatibility and distinct chemical properties. This protocol details two innovative methods for intracellular polymerization. The first one uses 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) as a photoinitiator for free radical polymerization under UV light (365 nm, 5 mW/cm2). The second method employs photoinduced electron transfer-reversible addition-fragmentation chain-transfer polymerization with visible light (470 nm, 100 mW/cm2). We further elaborate on isolating these intracellular polymers by streptavidin/biotin interaction or immobilized metal ion affinity chromatography for polymers tagged with biotin or histidine. The entire process, from polymerization to isolation, takes ~48 h. Moreover, the intracellular polymers thus generated demonstrate significant potential in enhancing actin polymerization, in bioimaging applications and as a novel avenue in cancer treatment strategies. The protocol extends to animal models, providing a comprehensive approach from cellular to systemic applications. Users are advised to have a basic understanding of organic synthesis and cell biology techniques.

4.
Science ; 383(6689): 1318-1325, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38513014

RESUMO

Plants are constantly exposed to volatile organic compounds (VOCs) that are released during plant-plant communication, within-plant self-signaling, and plant-microbe interactions. Therefore, understanding VOC perception and downstream signaling is vital for unraveling the mechanisms behind information exchange in plants, which remain largely unexplored. Using the hormone-like function of volatile terpenoids in reproductive organ development as a system with a visual marker for communication, we demonstrate that a petunia karrikin-insensitive receptor, PhKAI2ia, stereospecifically perceives the (-)-germacrene D signal, triggering a KAI2-mediated signaling cascade and affecting plant fitness. This study uncovers the role(s) of the intermediate clade of KAI2 receptors, illuminates the involvement of a KAI2ia-dependent signaling pathway in volatile communication, and provides new insights into plant olfaction and the long-standing question about the nature of potential endogenous KAI2 ligand(s).


Assuntos
Furanos , Hidrolases , Petunia , Piranos , Compostos Orgânicos Voláteis , Hidrolases/genética , Hidrolases/metabolismo , Transdução de Sinais , Compostos Orgânicos Voláteis/metabolismo , Petunia/fisiologia , Furanos/metabolismo , Piranos/metabolismo , Sesquiterpenos de Germacrano/metabolismo
5.
Nucleic Acids Res ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421638

RESUMO

TGF-ß signaling family plays an essential role to regulate fate decisions in pluripotency and lineage specification. How the action of TGF-ß family signaling is intrinsically executed remains not fully elucidated. Here, we show that HBO1, a MYST histone acetyltransferase (HAT) is an essential cell intrinsic determinant for TGF-ß signaling in human embryonic stem cells (hESCs). HBO1-/- hESCs fail to response to TGF-ß signaling to maintain pluripotency and spontaneously differentiate into neuroectoderm. Moreover, HBO1 deficient hESCs show complete defect in mesendoderm specification in BMP4-triggered gastruloids or teratomas. Molecularly, HBO1 interacts with SMAD4 and co-binds the open chromatin labeled by H3K14ac and H3K4me3 in undifferentiated hESCs. Upon differentiation, HBO1/SMAD4 co-bind and maintain the mesoderm genes in BMP4-triggered mesoderm cells while lose chromatin occupancy in neural cells induced by dual-SMAD inhibition. Our data reveal an essential role of HBO1, a chromatin factor to determine the action of SMAD in both human pluripotency and mesendoderm specification.

6.
Sci Immunol ; 9(92): eadk4348, 2024 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-38335269

RESUMO

TCRαß+CD8αα+ intraepithelial lymphocytes (CD8αα+ αß IELs) are a specialized subset of T cells in the gut epithelium that develop from thymic agonist selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αß T cells resulted in the near absence of CD8αα+ αß IELs. BCL6 was expressed by approximately 50% of CD8αα+ αß IELs and by the majority of thymic PD1+ IELps after agonist selection. Bcl6 deficiency blocked early IELp generation in the thymus, and its expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4+CD8+ double-positive thymocytes exhibited increased apoptosis during agonist selection and impaired IELp differentiation and maturation. Together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα+ αß IELs.


Assuntos
Linfócitos Intraepiteliais , Proteínas Proto-Oncogênicas c-bcl-6 , Receptores de Antígenos de Linfócitos T alfa-beta , Animais , Camundongos , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Mucosa Intestinal , Linfócitos Intraepiteliais/metabolismo , Camundongos Knockout , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo
7.
J Biomater Sci Polym Ed ; : 1-33, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340315

RESUMO

Radiological heart damage (RIHD) is damage caused by unavoidable irradiation of the heart during chest radiotherapy, with a long latency period and a progressively increasing proportion of delayed cardiac damage due to conventional doses of chest radiotherapy. There is a risk of inducing diseases such as acute/chronic pericarditis, myocarditis, delayed myocardial fibrosis and damage to the cardiac conduction system in humans, which can lead to myocardial infarction or even death in severe cases. This paper details the pathogenesis of RIHD and gives potential targets for treatment at the molecular and cellular level, avoiding the drawbacks of high invasiveness and immune rejection due to drug therapy, medical device implantation and heart transplantation. Injectable hydrogel therapy has emerged as a minimally invasive tissue engineering therapy to provide necessary mechanical support to the infarcted myocardium and to act as a carrier for various bioactive factors and cells to improve the cellular microenvironment in the infarcted area and induce myocardial tissue regeneration. Therefore, this paper combines bioactive factors and cellular therapeutic mechanisms with injectable hydrogels, presents recent advances in the treatment of cardiac injury after RIHD with different injectable gels, and summarizes the therapeutic potential of various types of injectable hydrogels as a potential solution.

8.
Mol Ther Methods Clin Dev ; 32(1): 101204, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38390556

RESUMO

Genetically engineered macrophages (GEMs) have emerged as an appealing strategy to treat cancers, but they are largely impeded by the cell availability and technical challenges in gene transfer. Here, we develop an efficient approach to generate large-scale macrophages from human induced pluripotent stem cells (hiPSCs). Starting with 1 T150 dish of 106 hiPSCs, more than 109 mature macrophages (iMacs) could be generated within 1 month. The generated iMacs exhibit typical macrophage properties such as phagocytosis and polarization. We then generate hiPSCs integrated with an IL-12 expression cassette in the AAVS1 locus to produce iMacs secreting IL-12, a strong proimmunity cytokine. hiPSC-derived iMacs_IL-12 prevent cytotoxic T cell exhaustion and activate T cells to kill different cancer cells. Furthermore, iMacs_IL-12 display strong antitumor effects in a T cell-dependent manner in subcutaneously or systemically xenografted mice of human lung cancer. Therefore, we provide an off-the-shelf strategy to produce large-scale GEMs for cancer therapy.

9.
Biomacromolecules ; 25(3): 1671-1681, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38354397

RESUMO

Nanoparticles (NPs) containing light-responsive polymers and imaging agents show great promise for controlled drug delivery. However, most light-responsive NPs rely on short-wavelength excitation, resulting in poor tissue penetration and potential cytotoxicity. Moreover, excessively sensitive NPs may prematurely release drugs during storage and circulation, diminishing their efficacy and causing off-target toxicity. Herein, we report visible-light-responsive NPs composed of an amphiphilic block copolymer containing responsive 4-acrylamide benzenesulfonyl azide (ABSA) and hydrophilic N,N'-dimethylacrylamide (DMA) units. The polymer pDMA-ABSA was loaded with the chemotherapy drug dasatinib and zinc tetraphenylporphyrin (ZnTPP). ZnTPP acted as an imaging reagent and a photosensitizer to reduce ABSA upon visible light irradiation, converting hydrophobic units to hydrophilic units and disrupting NPs to trigger drug release. These NPs enabled real-time fluorescence imaging in cells and exhibited synergistic chemophotodynamic therapy against multiple cancer cell lines. Our light-responsive NP platform holds great promise for controlled drug delivery and cancer theranostics, circumventing the limitations of traditional photosensitive nanosystems.


Assuntos
Portadores de Fármacos , Metaloporfirinas , Nanopartículas , Portadores de Fármacos/química , Azidas , Polímeros/química , Luz , Nanopartículas/química , Liberação Controlada de Fármacos
10.
BMC Anesthesiol ; 24(1): 14, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38172686

RESUMO

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain. METHODS: This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events. RESULTS: In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method. CONCLUSIONS: Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS. TRIAL REGISTRATION: The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).


Assuntos
Acetaminofen , Bloqueio Nervoso , Humanos , Acetaminofen/uso terapêutico , Cirurgia Torácica Vídeoassistida/métodos , Sufentanil , Oxicodona , Estudos Prospectivos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Analgésicos/uso terapêutico , Analgesia Controlada pelo Paciente/métodos , Tosse , Manitol
11.
Stem Cell Reports ; 19(2): 196-210, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38215759

RESUMO

Emergency myelopoiesis (EM) is essential in immune defense against pathogens for rapid replenishing of mature myeloid cells. During the EM process, a rapid cell-cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs) is critical. How the rapid proliferation of MPs during EM is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB)-mobilized hematopoietic stem/progenitor cells (HSPCs) with ATG7 knockdown or HSPCs derived from ATG7-/- human embryonic stem cells (hESCs) exhibit severe defect in proliferation during fate transition from HSPCs to MPs. Mechanistically, we show that ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation. Together, we reveal a previously unrecognized role of autophagy to regulate p53 for a rapid proliferation of MPs in human myelopoiesis.


Assuntos
Mielopoese , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células Mieloides , Autofagia/genética
12.
New Phytol ; 241(4): 1829-1839, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38058220

RESUMO

The biosynthesis of specialized metabolites is strictly regulated by environmental inputs such as the day-night cycle, but the underlying mechanisms remain elusive. In Petunia hybrida cv. Mitchell flowers, the biosynthesis and emission of volatile compounds display a diurnal pattern with a peak in the evening to attract nocturnal pollinators. Using petunia flowers as a model system, we found that chromatin level regulation, especially histone acetylation, plays an essential role in mediating the day-night oscillation of the biosynthetic gene network of specialized metabolites. By performing time-course chromatin immunoprecipitation assays for histone modifications, we uncovered that a specific group of genes involved in the regulation, biosynthesis, and emission of floral volatile compounds, which displays the greatest magnitude in day-night oscillating gene expression, is associated with highly dynamic histone acetylation marks H3K9ac and H3K27ac. Specifically, the strongest oscillating genes featured a drastic removal of histone acetylation marks at night, potentially to shut down the biosynthesis of floral volatile compounds during the morning when they are not needed. Inhibiting daytime histone acetylation led to a compromised evening induction of these genes. Overall, our study suggested an active role of chromatin modification in the diurnal oscillation of specialized metabolic network.


Assuntos
Histonas , Petunia , Histonas/metabolismo , Acetilação , Redes e Vias Metabólicas , Processamento de Proteína Pós-Traducional , Cromatina/metabolismo , Flores/fisiologia , Petunia/metabolismo , Regulação da Expressão Gênica de Plantas
14.
J Cell Physiol ; 239(1): 152-165, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37991435

RESUMO

Polycomb repressive complexes (PRCs) play critical roles in cell fate decisions during normal development as well as disease progression through mediating histone modifications such as H3K27me3 and H2AK119ub. How exactly PRCs recruited to chromatin remains to be fully illuminated. Here, we report that YTHDF1, the N6-methyladenine (m6 A) RNA reader that was previously known to be mainly cytoplasmic, associates with RNF2, a PRC1 protein that mediates H2AK119ub in human embryonic stem cells (hESCs). A portion of YTHDF1 localizes in the nuclei and associates with RNF2/H2AK119ub on a subset of gene loci related to neural development functions. Knock-down YTHDF1 attenuates H2AK119ub modification on these genes and promotes neural differentiation in hESCs. Our findings provide a noncanonical mechanism that YTHDF1 participates in PRC1 functions in hESCs.


Assuntos
Proteínas de Ciclo Celular , Células-Tronco Embrionárias Humanas , Proteínas de Ligação a RNA , Humanos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina , Células-Tronco Embrionárias Humanas/metabolismo , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Histonas/genética , Histonas/metabolismo
15.
Huan Jing Ke Xue ; 44(12): 6518-6528, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098380

RESUMO

Carbonaceous aerosols are an important component of fine particulate matter (PM2.5) in the atmosphere, having great impacts on air quality, human health, and the climate. In this study, PM2.5 samples were collected from November 2017 to October 2018 in a background site of Guangxi Province to investigate the potential impacts of biomass burning, an essential source of carbonaceous aerosols, on carbonaceous aerosols. Further, the composition of carbonaceous aerosols, sugar compounds, and the light absorption coefficient (babs) of water-soluble brown carbon (BrC) were also conducted. Considering the effect of the degradation of atmospheric levoglucosan (LG), the concentration of the corrected LG was quantified using the aging of air masses (AAM) index. Then, the contribution of biomass burning (BB) to organic carbon (OC) [BB-OC] was quantified using the corrected LG-derived molecular tracer method combined with the Bayesian mixing model. Here, we further explored the potential sources of water-soluble BrC using correlation analysis. In this research, the mean AAM index was 0.40±0.28 during the study period, indicating that the atmospheric LG had undergone a photochemical degradation process. The characteristic ratio combined with the Bayesian mixing model indicated that the crop straw (i.e., corn, rice, and sugarcane straw) was the dominant biomass fuel type in the Guangxi Region, contributing 22%, 23%, and 18% of OC without the correction of LG and 16%, 21%, and 17% with the corrected LG concentration, respectively. The neglection of LG degradation led to the underestimation of BB-OC, in which the BB-OC values with and without correction were 49.0% and 21.1%, respectively. Here, the annual mean babs of water-soluble BrC was (8.7±10.7) Mm-1, and its main sources were BB, fossil fuel combustion, and vegetation emission.

16.
Org Lett ; 25(48): 8733-8738, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-37991739

RESUMO

A photoredox-catalyzed approach for the difluoroalkylation of amino acids was achieved through simultaneous decarboxylation and defluorination processes. This innovative protocol employs commonly available amino acids and trifluoroacetophenones as the primary starting materials, eliminating the necessity for preactivation. This strategy has enabled the synthesis of several difluoroketone functionalized amines in moderate to impressive yields. These synthesized compounds are presented as foundational molecules for subsequent modification. The underlying mechanism for the transformation is anchored in a single electron transfer (SET) radical pathway.

17.
Kaohsiung J Med Sci ; 39(11): 1106-1118, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37698291

RESUMO

Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-ß and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial-mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-ß and MST1 were applied to validate the roles of TGF-ß and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-ß expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-ß in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-ß to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Piroptose , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-37658836

RESUMO

HIV-1CRF08_BC is the most prevalent epidemic subtype among heterosexual (HET) and intravenous drug users (IDUs) in Kunming, Yunnan. Using the pol region of gene sequences derived from molecular epidemiological surveys, we developed a molecular transmission network for the purpose of analyzing its epidemiological characteristics, assessing its epidemiological trends, identifying its potential transmission relationships, and developing targeted interventions. HyPhy 2.2.4 was used to calculate pairwise genetic distances between sequences; GraphPad-Prism 8.0 was employed to determine the standard genetic distance; and Cytoscope 3.7.2 was applied to visualize the network. We used the network analysis tools to investigate network characteristics and the Molecular Complex Detection (MCODE) tool to observe the growth of the network. We utilized a logistic regression model to examine the factors influencing clustering and a zero-inflated Poisson model to investigate the factors influencing potential transmission links. At the standard genetic distance threshold of 0.008, 406 out of 858 study participants were clustered in 132 dissemination networks with a total network linkage of 868, and the number of links per sequence ranged from 1 to 19. The MCODE analysis identified three significant modular clusters in the networks, with network scores ranging from 4.9 to 7. In models of logistic regression, HET, middle-aged and elderly individuals, and residents of northern and southeastern Kunming were more likely to enter the transmission network. According to the zero-inflated Poisson model, age, transmission category, sampling year, marital status, and CD4+ T level had a significant effect on the size of links. The molecular clusters in Kunming's molecular transmission network are specific and aggregate to a certain extent. HIV-1 molecular network analysis provided information on local transmission characteristics, and these findings helped to determine the priority of transmission-reduction interventions.

19.
New Phytol ; 240(2): 710-726, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37547968

RESUMO

MicroRNAs (miRNAs) play crucial roles in regulating plant development and stress responses. However, the functions and mechanism of intronic miRNAs in plants are poorly understood. This study reports a stress-responsive RNA splicing mechanism for intronic miR400 production, whereby miR400 modulates reactive oxygen species (ROS) accumulation and improves plant tolerance by downregulating its target expression. To monitor the intron splicing events, we used an intronic miR400 splicing-dependent luciferase transgenic line. Luciferase activity was observed to decrease after high cadmium concentration treatment due to the retention of the miR400-containing intron, which inhibited the production of mature miR400. Furthermore, we demonstrated that under Cd treatments, Pentatricopeptide Repeat Protein 1 (PPR1), the target of miR400, acts as a positive regulator by inducing ROS accumulation. Ppr1 mutation affected the Complex III activity in the electron transport chain and RNA editing of the mitochondrial gene ccmB. This study illustrates intron splicing as a key step in intronic miR400 production and highlights the function of intronic miRNAs as a 'signal transducer' in enhancing plant stress tolerance.


Assuntos
Arabidopsis , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Arabidopsis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Íntrons/genética , Splicing de RNA/genética , Regulação da Expressão Gênica de Plantas
20.
Stem Cells Transl Med ; 12(8): 553-568, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37399126

RESUMO

Human embryonic stem cells-derived neural progenitor cells (hESCs-NPCs) transplantation holds great potential to treat stroke. We previously reported that delayed secondary degeneration occurs in the ventroposterior nucleus (VPN) of ipsilateral thalamus after distal branch of middle cerebral artery occlusion (dMCAO) in adult male Sprague-Dawley (SD) rats. In this study, we investigate whether hESCs-NPCs would benefit the neural recovery of the secondary damage in the VPN after focal cerebral infarction. Permanent dMCAO was performed with electrocoagulation. Rats were randomized into Sham, dMCAO groups with or without hESCs-NPCs treatment. HESCs-NPCs were engrafted into the peri-infarct regions of rats at 48 h after dMCAO. The transplanted hESCs-NPCs survive and partially differentiate into mature neurons after dMCAO. Notably, hESCs-NPCs transplantation attenuated secondary damage of ipsilateral VPN and improved neurological functions of rats after dMCAO. Moreover, hESCs-NPCs transplantation significantly enhanced the expression of BDNF and TrkB and their interaction in ipsilateral VPN after dMCAO, which was reversed by the knockdown of TrkB. Transplantated hESCs-NPCs reconstituted thalamocortical connection and promoted the formation of synapses in ipsilateral VPN post-dMCAO. These results suggest that hESCs-NPCs transplantation attenuates secondary damage of ipsilateral thalamus after cortical infarction, possibly through activating BDNF/TrkB pathway, enhancing thalamocortical projection, and promoting synaptic formation. It provides a promising therapeutic strategy for secondary degeneration in the ipsilateral thalamus post-dMCAO.


Assuntos
Células-Tronco Embrionárias , Infarto da Artéria Cerebral Média , Células-Tronco Neurais , Humanos , Células-Tronco Embrionárias/transplante , Animais , Ratos , Ratos Sprague-Dawley , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/terapia , Células-Tronco Neurais/transplante , Diferenciação Celular , Movimento Celular , Transdução de Sinais , Neuroproteção , Tálamo/metabolismo
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