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1.
World J Gastroenterol ; 30(10): 1431-1449, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596485

RESUMO

BACKGROUND: Serotonin receptor 2B (5-HT2B receptor) plays a critical role in many chronic pain conditions. The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea (IBS-D) was investigated in the present study. AIM: To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D. METHODS: Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls. The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores. The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint. Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1 (TRPV1) expression were examined following 5-HT2B receptor antagonist administration. Changes in visceral sensitivity after administration of the TRPV1 antagonist were recorded. RESULTS: Here, we observed greater expression of the 5-HT2B receptor in the colonic mucosa of patients with IBS-D than in that of controls, which was correlated with abdominal pain scores. Intracolonic instillation of acetic acid and wrap restraint induced obvious chronic visceral hypersensitivity and increased fecal weight and fecal water content. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia.Moreover, the percentage of 5-HT2B receptor-immunoreactive (IR) cells surrounded by TRPV1-positive cells (5-HT2B receptor I+) and total 5-HT2B receptor IR cells (5-HT2B receptor IT) in IBS-D rats was significantly reduced by the administration of a 5-HT2B receptor antagonist. CONCLUSION: Our finding that increased expression of the 5-HT2B receptor contributes to visceral hyperalgesia by inducing TRPV1 expression in IBS-D patients provides important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.


Assuntos
Síndrome do Intestino Irritável , Humanos , Ratos , Animais , Síndrome do Intestino Irritável/patologia , Receptor 5-HT2B de Serotonina , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Serotonina/metabolismo , Diarreia/etiologia , Receptores de Serotonina , Dor Abdominal/etiologia , Dor Abdominal/metabolismo , Acetatos
2.
Int J Mol Med ; 53(5)2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38577932

RESUMO

Pyroptosis, a programmed cell death marked by lytic and inflammatory characteristics, plays a crucial role in non­infectious inflammation­related diseases but can lead to detrimental outcomes when dysregulated. Stem cells have emerged as key players in modulating pyroptosis through paracrine signaling, offering a novel avenue for tissue repair and regeneration. The present review delved into previous studies elucidating the intricate interplay between stem cells and pyroptosis, emphasizing the potential of stem cell­based therapies in regulating pyroptotic pathways. The exploration of this dynamic interaction holds promise for developing strategies to harness stem cells for effective tissue repair and regeneration in the context of inflammation­related diseases.


Assuntos
Apoptose , Piroptose , Humanos , Células-Tronco , Inflamação
3.
Neurobiol Dis ; : 106505, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642715

RESUMO

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aß deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.

4.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38413234

RESUMO

Recent Studies have shown that the formation of the primary cilium is associated with a specific cellular organelle known as the midbody remnant(MBR), which is a point-like organelle formed by shedding of the midbody at the end of mitosis. MBRs move along the cell surface close to the center body, and regulate it to form primary cilia at the top of centriole. Primary cilia can act as an organelle to inhibit tumorigenesis, and it is lost in a variety of tumors. Studies have shown that the accumulation of MBRs in tumor cells affects ciliogenesis; in addition, both MBRs and primary cilia are degraded in tumor cells through the autophagy pathway, and MBRs can also transfer tumor signaling pathway factors to primary cilia affecting tumorigenesis. In this article, the basic structure and the formation process of MBR and primary cilia are reviewed, the mechanism of MBRs regulating ciliogenesis is elaborated, the significance of MBR-mediated ciliogenesis in tumorigenesis and its potential as a target for cancer treatment are discussed.

5.
DNA Cell Biol ; 43(3): 141-151, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38215233

RESUMO

Primary cilia are microtubule-based organelles that mediate various biological processes. Pancreatic cells are typically ciliated; however, the role of primary cilia in acute pancreatitis (AP) is largely unknown. Here, we report that the loss of primary cilia, mediated by SHCBP1 (SHC1 binding protein), exerted a provocative effect on AP. Primary cilia are extensively lost in inflamed pancreatic cells in vitro and in mouse tissues with AP in vivo. Abrogation of primary cilia aggravated lipopolysaccharide (LPS)-induced inflammation in pancreatic cells. Mechanistically, AP induced the overexpression of SHCBP1 mitotic factor, which is localized to the base of primary cilia. SHCBP1 deficiency relieved LPS- and cerulein-induced pancreatitis by preventing the loss of primary cilia in vitro and in vivo. Collectively, we reveal that inflammation-induced loss of primary cilia aggravates AP. Furthermore, abrogating SHCBP1 to prevent primary cilia loss is an efficient strategy to combat AP.


Assuntos
Pancreatite , Camundongos , Animais , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Pancreatite/prevenção & controle , Lipopolissacarídeos/toxicidade , Doença Aguda , Cílios/metabolismo , Inflamação
6.
Bioorg Chem ; 142: 106951, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37924755

RESUMO

Thrombotic diseases, such as myocardial infarction, stroke, and deep vein thrombosis, severely threaten human health, and anticoagulation is an effective way to prevent such illnesses. However, most anticoagulant drugs in the clinic have different bleeding risks. Previous studies have shown that coagulation factor XI is an ideal target for safe anticoagulant drug development. Here, we designed the FXIa inhibitory peptide DX-88mut by replacing Loop1 (DGPCRAAHPR) and Loop2 (IYGGC) in DX-88, which is a clinical drug targeting PKa for the treatment of hereditary angioedema, using Loop1 (TGPCRAMISR) and Loop2 (FYGGC) in the FXIa inhibitory peptide PN2KPI, respectively. DX-88mut selectively inhibited FXIa against a panel of serine proteases with an IC50 value of 14.840 ± 0.453 nM, dose-dependently prolonged APTT in mouse, rat and human plasma, and potently inhibited FeCl3-induced carotid artery thrombosis in mice at a dose of 1 µmol/kg. Additionally, DX-88mut did not show a significant bleeding risk at a dose of 5 µmol/kg. Taken together, these results show that DX-88mut is a potential candidate for the development of a novel antithrombotic agent.


Assuntos
Fator XIa , Trombose , Humanos , Ratos , Camundongos , Animais , Fator XIa/metabolismo , Fator XIa/farmacologia , Coagulação Sanguínea , Anticoagulantes/farmacologia , Trombose/tratamento farmacológico , Peptídeos/farmacologia
7.
Front Oncol ; 13: 1276310, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053654

RESUMO

Cisplatin is a common anticancer drug able to kill tumor cells, but it causes adverse reactions in the kidney, digestive tract, and other systems. The antitumor effects of cisplatin are mainly due to its ability to bind to the DNA in tumor cells to prevent replication, thereby reducing RNA and protein syntheses, leading to cell damage and death. Cisplatin has a wide range of applications; it can be used to treat cervical, thyroid, ovarian, and other cancers. Cisplatin has a beneficial therapeutic effect, but its therapeutic selectivity is poor. In addition to eliminating diseased target cells, cisplatin can damage normal cells; in women of reproductive age being treated for cancer, cisplatin can lead to ovarian function impairment, premature ovarian failure (POF), and/or infertility. Therefore, reducing the adverse effects of cisplatin on ovarian function is an important topic in clinical research. In this paper, we explore the research progress on the POF caused by cisplatin treatment.

8.
Ear Nose Throat J ; : 1455613231199699, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37800471

RESUMO

An uncommon benign condition in neonates, known as congenital epiglottic cyst, can lead to symptoms such as neonatal dyspnea, laryngeal stridor, and, in severe cases, even pose a potential threat of asphyxia-related mortality. A congenital epiglottic cyst is one of the neonatal emergencies. Fibrolaryngoscopy is the predominant method of diagnosis, and early identification, diagnosis, as well as treatment are the key points. Successful endoscopic ablation of congenital epiglottic cysts in 3 newborns was achieved through the utilization of a low-temperature plasma radiofrequency ablation system. Consequently, the purpose of this case report is to assist pediatric emergency physicians in the timely identification of congenital epiglottic cysts with the potential risk of mortality and to provide additional experience in clinical management.

9.
Sensors (Basel) ; 23(20)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37896707

RESUMO

In the domain of optical fiber distributed acoustic sensing, the persistent challenge of extending sensing distances while concurrently improving spatial resolution and frequency response range has been a complex endeavor. The amalgamation of pulse compression and frequency division multiplexing methodologies has provided certain advantages. Nevertheless, this approach is accompanied by the drawback of significant bandwidth utilization and amplified hardware investments. This study introduces an innovative distributed optical fiber acoustic sensing system aimed at optimizing the efficient utilization of spectral resources by combining compressed pulses and frequency division multiplexing. The system continuously injects non-linear frequency modulation detection pulses spanning various frequency ranges. The incorporation of non-uniform frequency division multiplexing augments the vibration frequency response spectrum. Additionally, nonlinear frequency modulation adeptly reduces crosstalk and enhances sidelobe suppression, all while maintaining a favorable signal-to-noise ratio. Consequently, this methodology substantially advances the spatial resolution of the sensing system. Experimental validation encompassed the multiplexing of eight frequencies within a 120 MHz bandwidth. The results illustrate a spatial resolution of approximately 5 m and an expanded frequency response range extending from 1 to 20 kHz across a 16.3 km optical fiber. This achievement not only enhances spectral resource utilization but also reduces hardware costs, making the system even more suitable for practical engineering applications.

10.
Cell Commun Signal ; 21(1): 233, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723552

RESUMO

Cancer immunotherapy has been proven to be clinically effective in multiple types of cancers. Lymphocyte function-associated antigen 1 (LFA-1), a member of the integrin family of adhesion molecules, is expressed mainly on αß T cells. LFA-1 is associated with tumor immune responses, but its exact mechanism remains unknown. Here, two kinds of mice tumor model of LFA-1 knockout (LFA-1-/-) mice bearing subcutaneous tumor and Apc Min/+;LFA-1-/- mice were used to confirm that LFA-1 knockout resulted in inhibition of tumor growth. Furthermore, it also demonstrated that the numbers of regulatory T cells (Treg cells) in the spleen, blood, mesenteric lymph nodes were decreased in LFA-1-/- mice, and the numbers of Treg cells in mesenteric lymph nodes were also decreased in Apc Min/+;LFA-1-/- mice compared with Apc Min/+ mice. LFA-1 inhibitor (BIRT377) was administered to subcutaneous tumor-bearing LFA-1+/+ mice, and the results showed that the tumor growth was inhibited and the number of Treg cells was reduced. The analysis of TIMER tumor database indicated that LFA-1 expression is positively associated with Treg cells and TNM stage. Conclusively, this suggests that LFA-1 knockout would inhibit tumor growth and is correlated with Treg cells. LFA-1 may be one potential target for cancer immunotherapy. Video Abstract.


Assuntos
Antígeno-1 Associado à Função Linfocitária , Neoplasias , Animais , Camundongos , Linfócitos T Reguladores , Baço , Bases de Dados Factuais
11.
Front Pediatr ; 11: 1163368, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576136

RESUMO

Objective: This study aimed to retrospectively describe the unplanned retreatment of dental general anesthesia (DGA) in children with severe early childhood caries (S-ECC) and explore potential factors that may influence the outcome of DGA treatment. Methods: Medical records of children with S-ECC who received DGA treatment were screened, and necessary data were extracted. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the DGA survival rate and explore the potential factors affecting the success rate of DGA treatment. Results: Medical records of 852 children were included; 509 (59.7%) children with 1,212 (10.7%) teeth underwent unplanned retreatment. Restoration failure (30.12%) and new caries (29.46%) accounted for the most significant proportion of all failures. The median survival times were 510 and 1,911 days at the child and tooth levels, respectively. Unplanned retreatment risk was associated with the age of S-ECC children, frequency of follow-up, and fluoride application (hazard ratio = 0.97, 0.78, 0.69, P < 0.001). Conclusion: The treatment outcome of DGA administered to children with S-ECC was satisfactory at the tooth level from the perspective of the incidence of unplanned retreatment. Restoration failure was the main reason for the high unplanned retreatment rate. Strategies for a better outcome of DGA include improving the professional knowledge and skills of pediatric dentists and enhancing compliance of parents/patients. Health education and regular topical fluoride application may improve the success rate of DGA treatment.

12.
Neurol Ther ; 12(5): 1745-1758, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37490234

RESUMO

INTRODUCTION: Similar white matter hyperintensities (WMH) burden may have varied cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study aimed to evaluate whether blood-brain barrier (BBB) permeability is associated with cognitive impairment (CI) heterogeneity in patients with WMH. METHODS: We recruited 51 participants with WMH. We evaluated WMH burden using the Fazekas scale and WMH volume on structural magnetic resonance imaging (MRI), and assessed BBB permeability using dynamic contrast-enhanced (DCE)-MRI. We used permeability-surface area product (PS) from the Patlak model to represent BBB permeability. All patients underwent Mini-Mental State Examination (MMSE), Boston Naming Test (BNT) and animal verbal fluency test (VFT) for cognitive assessment. We divided patients into CI and non-CI groups based on their MMSE scores (< 27 or ≥ 27) and used multiple linear regression models to investigate the associations between MRI parameters and cognitive function. RESULTS: Patients in the two groups did not differ in Fazekas scores and WMH volume. However, patients in the CI group showed significantly higher PS in the WMH regions than those in non-CI group (1.89 × 10-3 versus 1.00 × 10-3, p = 0.032 in periventricular WMH [PVWMH]; 1.27 × 10-3 versus 0.74 × 10-3, p = 0.043 in deep WMH [DWMH]), indicating the breakdown of BBB in the CI group. In all patients with WMH, increased BBB permeability in PVWMH and DWMH was significantly associated with lower cognitive and language function after adjustment for age, education level (EL) and intracranial volume (ICV). In the CI group, this correlation remained significant. WMH volume was not associated with cognitive performance in either all patients or those with CI. CONCLUSION: BBB impairment might be a more sensitive indicator for cognitive and language dysfunction than WMH volume in patients with WMH and possibly explains the heterogeneity of cognitive performance in patients with similar WMH burden.

13.
Front Psychol ; 14: 1120758, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168428

RESUMO

Introduction: Previous studies have defined "workaholic" effort as "bad effort" while work engagement is defined as "good effort." Active overtime is a mapping of work effort, but at this stage there is still relatively little exploration of the motivation behind "good effort" in the Chinese context. Methods: This study explores the reasons that promote employees' initiative to perform overtime work in Chinese enterprises based on the two-factor theory. The study mainly used data empirical research approaches, including exploratory factor analysis, validation factor analysis, and data modeling. The questionnaire scale was developed based on factors that have been proven to be of high reliability and validity. The data are mainly for employees who are currently employed in Chinese companies. Results and discussion: We received a total of 1741 valid questionnaires, which provided a good database for this study. The results of the study show that both motivational and hygiene factors can positively promote employees' motivation to intentionally work overtime to a certain extent. Among them, overtime culture, institutional agreement, good physical office environment, career growth, financial rewards, and work challenges can positively promote motivation to work overtime. Work stress can increase the frequency and intensity of overtime work, but negatively promote motivation to work overtime. The study helps to improve enterprise management, optimize work design, and enhance psychological satisfaction.

14.
Entropy (Basel) ; 25(5)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37238566

RESUMO

Blockchain technology affords data integrity protection and building trust mechanisms in transactions for distributed networks, and, therefore, is seen as a promising revolutionary information technology. At the same time, the ongoing breakthrough in quantum computation technology contributes toward large-scale quantum computers, which might attack classic cryptography, seriously threatening the classic cryptography security currently employed in the blockchain. As a better alternative, a quantum blockchain has high expectations of being immune to quantum computing attacks perpetrated by quantum adversaries. Although several works have been presented, the problems of impracticality and inefficiency in quantum blockchain systems remain prominent and need to be addressed. First, this paper develops a quantum-secure blockchain (QSB) scheme by introducing a consensus mechanism-quantum proof of authority (QPoA) and an identity-based quantum signature (IQS)-wherein QPoA is used for new block generation and IQS is used for transaction signing and verification. Second, QPoA is developed by adopting a quantum voting protocol to achieve secure and efficient decentralization for the blockchain system, and a quantum random number generator (QRNG) is deployed for randomized leader node election to protect the blockchain system from centralized attacks like distributed denial of service (DDoS). Compared to previous work, our scheme is more practical and efficient without sacrificing security, greatly contributing to better addressing the challenges in the quantum era. Extensive security analysis demonstrates that our scheme provides better protection against quantum computing attacks than classic blockchains. Overall, our scheme presents a feasible solution for blockchain systems against quantum computing attacks through a quantum strategy, contributing toward quantum-secured blockchain in the quantum era.

15.
Tree Physiol ; 43(8): 1444-1453, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37104646

RESUMO

GRAS transcription factors belong to the plant-specific protein family. They are not only involved in plant growth and development but also in plant responses to a variety of abiotic stresses. However, to date, the SCL32(SCARECROW-like 32) gene conferring the desired resistance to salt stresses has not been reported in plants. Here, ThSCL32, a homologous gene of ArabidopsisthalianaAtSCL32, was identified. ThSCL32 was highly induced by salt stress in Tamarix hispida. ThSCL32 overexpression in T. hispida gave rise to improved salt tolerance. ThSCL32-silenced T. hispida plants were more sensitive to salt stress. RNA-seq analysis of transient transgenic T. hispida overexpressing ThSCL32 revealed significantly enhanced ThPHD3 (prolyl-4-hydroxylase domain 3 protein) gene expression. ChIP-PCR further verified that ThSCL32 probably binds to the novel cis-element SBS (ACGTTG) in the promoter of ThPHD3 to activate its expression. In brief, our results suggest that the ThSCL32 transcription factor is involved in salt tolerance in T. hispida by enhancing ThPHD3 expression.


Assuntos
Tolerância ao Sal , Tamaricaceae , Tolerância ao Sal/genética , Tamaricaceae/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Expressão Gênica , Regulação da Expressão Gênica de Plantas
16.
Nat Commun ; 14(1): 2280, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37080992

RESUMO

Ribonucleases (RNases) are responsible for RNA metabolism. RNase J, the core enzyme of the RNA degradosome, plays an essential role in global mRNA decay. Emerging evidence showed that the RNase J of Mycobacterium tuberculosis (Mtb-RNase J) could be an excellent target for treating Mtb infection. Here, crystal structures of Mtb-RNase J in apo-state and complex with the single-strand RNA reveal the conformational change upon RNA binding and hydrolysis. Mtb-RNase J forms an active homodimer through the interactions between the ß-CASP and the ß-lactamase domain. Knockout of RNase J slows the growth rate and changes the colony morphologies and cell length in Mycobacterium smegmatis, which is restored by RNase J complementation. Finally, RNA-seq analysis shows that the knockout strain significantly changes the expression levels of 49 genes in metabolic pathways. Thus, our current study explores the structural basis of Mtb-RNase J and might provide a promising candidate in pharmacological treatment for tuberculosis.


Assuntos
Mycobacterium tuberculosis , Ribonucleases , Ribonucleases/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , RNA/metabolismo , Ribonuclease Pancreático/metabolismo , Hidrólise
17.
Natl Sci Rev ; 10(5): nwad045, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37056443

RESUMO

Physical characteristics of terrains, such as softness and friction, provide essential information for legged robots to avoid non-geometric obstacles, like mires and slippery stones, in the wild. The perception of such characteristics often relies on tactile perception and vision prediction. Although tactile perception is more accurate, it is limited to close-range use; by contrast, establishing a supervised or self-supervised contactless prediction system using computer vision requires adequate labeled data and lacks the ability to adapt to the dynamic environment. In this paper, we simulate the behavior of animals and propose an unsupervised learning framework for legged robots to learn the physical characteristics of terrains, which is the first report to manage it online, incrementally and with the ability to solve cognitive conflicts. The proposed scheme allows robots to interact with the environment and adjust their cognition in real time, therefore endowing robots with the adaptation ability. Indoor and outdoor experiments on a hexapod robot are carried out to show that the robot can extract tactile and visual features of terrains to create cognitive networks independently; an associative layer between visual and tactile features is created during the robot's exploration; with the layer, the robot can autonomously generate a physical segmentation model of terrains and solve cognitive conflicts in an ever-changing environment, facilitating its safe navigation.

18.
AIDS Res Hum Retroviruses ; 39(12): 681-687, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36943286

RESUMO

In recent years, men who have sex with men (MSM) have been identified as the primary source of HIV-1 transmission in Hebei Province, China. Co-circulation of multiple subtypes in HIV-1 positive MSM populations may contribute to the emergence of the second generation of recombinant HIV-1 strains, indicating the occurrence of dual infections or superinfections in MSM populations. Thus, the discovery of new recombinant strains is important to indicate the appearance of multiple infected individuals and the prevalence caused by changes in the parent strains. In this study, we present two new unique recombinant forms (URFs) from two HIV-1-positive subjects (HB070052 and HB070056) infected through homosexual contact in Hebei Province, China. The near full-length genome of the two URFs revealed that HB070052 was divided into seven segments by six breakpoints in the gag, pol, vif, and vpr genes; HB070056 was separated into five fragments by four breakpoints, with two regions of CRF07_BC inserted into a CRF01_AE backbone's gag, pol regions. The subregion tree showed CRF01_AE segments were traced back to the cluster 4 and 6 of the CRF01_AE phylogenetic tree, which were prevalent among HIV-1 infections through MSM in China. The continued emergence of the novel CRF01_AE/CRF07_BC recombinant forms indicates the HIV-1 epidemic is complex and long-term surveillance of recombinant strains is necessary among MSM in this region.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , HIV-1/genética , Filogenia , Recombinação Genética , Genoma Viral , Análise de Sequência de DNA , China/epidemiologia , Genótipo
19.
Biomed Pharmacother ; 158: 114206, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36916433

RESUMO

The term type III diabetes (T3DM) has been proposed for Alzheimer's disease (AD) due to the shared molecular and cellular features between type 2 diabetes (T2DM) and insulin resistance-associated memory deficits and cognitive decline in elderly individuals. Astrocytes elicit neuroprotective or deleterious effects in AD progression and severity. Patients with T2DM are at a high risk of cognitive impairment, and targeting astrocytes might be promising in alleviating neurodegeneration in the diabetic brain. Recent studies focusing on cell-specific activities in the brain have revealed the important role of astrocytes in brain metabolism (e.g., glucose metabolism, lipid metabolism), neurovascular coupling, synapses, and synaptic plasticity. In this review, we discuss how astrocytes and their dysfunction result in multiple pathological and clinical features of AD and T2DM from a metabolic perspective and the potential comorbid mechanism in these two diseases from the perspective of astrocytes.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Idoso , Doença de Alzheimer/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Astrócitos/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo
20.
Adv Sci (Weinh) ; 10(10): e2300282, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36755201

RESUMO

Despite the success of small interfering RNA (siRNA) in clinical settings and its potential value in human immunodeficiency virus (HIV) therapy, the rapid clearance and absence of precise delivery to target cells still hinder the therapeutic effect of siRNA. Herein, a new system, which can escape immune recognition, has HIV-1 neutralizing capacity, and the ability to deliver siRNA specifically into HIV-1-infected cells, is constructed by functionalizing siRNA delivery lipid nanoparticles with the lymphocyte membrane and 12p1. The constructed system is shown to escape uptake by the mononuclear phagocyte system. The constructed system exhibits strong binding ability with gp120, thus displaying distinguished neutralizing breadth and potency. The constructed system neutralizes all tested HIV-1 pseudotyped viruses with a geometric mean 80% inhibitory concentration (IC80) of 29.75 µg mL-1 and inhibits X4-tropic HIV-1 with an IC80 of 64.20 µg mL-1 , and R5-tropic HIV-1 with an IC80 of 16.39 µg mL-1 . The new system also specifically delivers siRNA into the cytoplasm of HIV-1-infected cells and exhibits evident gene silencing of tat and rev. Therefore, this new system can neutralize HIV-1 and deliver siRNA selectively into HIV-1-infected cells and may be a promising therapeutic candidate for the precise therapy of HIV.


Assuntos
Infecções por HIV , HIV-1 , Nanopartículas , Humanos , HIV-1/genética , HIV-1/metabolismo , RNA Interferente Pequeno/metabolismo , Linfócitos , Infecções por HIV/terapia , Infecções por HIV/genética
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