Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 222
Filter
1.
IUBMB Life ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38721892

ABSTRACT

Low back pain is a common clinical symptom of intervertebral disc degeneration (IVDD), which seriously affects the quality of life of the patients. The abnormal apoptosis and senescence of nucleus pulposus cells (NPCs) play important roles in the pathogenesis of IVDD. PHLDA2 is an imprinted gene related to cell apoptosis and tumour progression. However, its role in NPC degeneration is not yet clear. Therefore, this study was set to explore the effects of PHLDA2 on NPC senescence and apoptosis and the underlying mechanisms. The expression of PHLDA2 was examined in human nucleus pulposus (NP) tissues and NPCs. Immunohistochemical staining, magnetic resonance imaging imaging and western blot were performed to evaluate the phenotypes of intervertebral discs. Senescence and apoptosis of NPCs were assessed by SA-ß-galactosidase, flow cytometry and western blot. Mitochondrial function was investigated by JC-1 staining and transmission electron microscopy. It was found that the expression level of PHLDA2 was abnormally elevated in degenerated human NP tissues and NPCs. Furthermore, knockdown of PHLDA2 can significantly inhibit senescence and apoptosis of NPCs, whereas overexpression of PHLDA2 can reverse senescence and apoptosis of NPCs in vitro. In vivo experiment further confirmed that PHLDA2 knockdown could alleviate IVDD in rats. Knockdown of PHLDA2 could also reverse senescence and apoptosis in IL-1ß-treated NPCs. JC-1 staining indicated PHLDA2's knockdown impaired disruption of the mitochondrial membrane potential and also ameliorated superstructural destruction of NPCs as showed by transmission electron microscopy. Finally, we found the PHLDA2 knockdown promoted Collagen-II expression and suppressed MMP3 expression in NPCs by repressing wnt/ß-catenin pathway. In conclusion, the results of the present study showed that PHLDA2 promotes IL-1ß-induced apoptosis and senescence of NP cells via mitochondrial route by activating the Wnt/ß-catenin pathway, and suggested that therapy targeting PHLDA2 may provide valuable insights into possible IVDD therapies.

2.
Psychol Sci ; : 9567976241243367, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38657276

ABSTRACT

The neural mechanisms underpinning the dynamic switching of a listener's attention between speakers are not well understood. Here we addressed this issue in a natural conversation involving 21 triadic adult groups. Results showed that when the listener's attention dynamically switched between speakers, neural synchronization with the to-be-attended speaker was significantly enhanced, whereas that with the to-be-ignored speaker was significantly suppressed. Along with attention switching, semantic distances between sentences significantly increased in the to-be-ignored speech. Moreover, neural synchronization negatively correlated with the increase in semantic distance but not with acoustic change of the to-be-ignored speech. However, no difference in neural synchronization was found between the listener and the two speakers during the phase of sustained attention. These findings support the attenuation model of attention, indicating that both speech signals are processed beyond the basic physical level. Additionally, shifting attention imposes a cognitive burden, as demonstrated by the opposite fluctuations of interpersonal neural synchronization.

4.
Cell Death Dis ; 15(3): 236, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38553452

ABSTRACT

Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial-mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.


Subject(s)
RNA, Long Noncoding , Stomach Neoplasms , Humans , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Energy Metabolism , Feedback , Gene Expression Regulation, Neoplastic , Protein Biosynthesis , RNA, Long Noncoding/metabolism , Stomach Neoplasms/pathology
5.
Article in English | MEDLINE | ID: mdl-38194385

ABSTRACT

Most memristor-based neural network circuits consider only a single pattern of overshadowing or emotion, but the relationship between overshadowing and emotion is ignored. In this article, a memristor-based neural network circuit of associative memory with overshadowing and emotion congruent effect is designed, and overshadowing under multiple emotions is taken into account. The designed circuit mainly consists of an emotion module, a memory module, an inhibition module, and a feedback module. The generation and recovery of different emotions are realized by the emotion module. The functions of overshadowing under different emotions and recovery from overshadowing are achieved by the inhibition module and the memory module. Finally, the blocking caused by long-term overshadowing is implemented by the feedback module. The proposed circuit can be applied to bionic emotional robots and offers some references for brain-like systems.

6.
Cell Mol Life Sci ; 81(1): 24, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38212432

ABSTRACT

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Nucleus Pulposus , Rats , Animals , Intervertebral Disc Degeneration/metabolism , Nucleus Pulposus/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases/metabolism , Intervertebral Disc/metabolism , Cellular Senescence
7.
Inorg Chem ; 63(5): 2776-2786, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38266170

ABSTRACT

Developing efficient heterogeneous catalysts for chemical fixation of CO2 to produce high-value-added chemicals under mild conditions is highly desired but still challenging. Herein, we first reported an approach to prepare a novel catalyst (Ag@NCNFs), featuring Ag nanoparticles (NPs) embedded within porous nitrogen-doped carbon nanofibers (NCNFs), via growing a Ag metal-organic framework on one-dimensional electrospun nanofibers followed by pyrolysis. Benefiting from the abundant nitrogen species and porous structure, Ag NPs is well dispersed in the obtained Ag@NCNFs. Catalytic studies indicated that Ag@NCNFs exhibited excellent catalytic activity for the three-component coupling reaction of CO2, secondary amines, and propargylic alcohols to generate ß-oxopropylcarbamates under mild conditions with a turnover number (TON) of 16.2, and it can be recycled and reused at least 5 times without an obvious decline in catalytic activity. The reaction mechanism was clearly clarified by FTIR, NMR, 13C isotope labeling, control experiments, and density functional theory calculations. The results suggest that Ag@NCNFs and 1,8-diazabicyclo[5.4.0]undec-7-ene can synergistically activate propargylic alcohol to react with CO2, and then the generated α-alkylidene cyclic carbonate was invaded by secondary amine to produce ß-oxopropylcarbamate. Importantly, to the best of our knowledge, this is the first experimental and theoretical investigation on this reaction.

8.
Phys Chem Chem Phys ; 26(2): 1023-1029, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38093671

ABSTRACT

In light-harvesting complex II of plants, the two lutein pigments (LUT1 and LUT2) are always paired and an energy transfer pathway between them is believed to exist. However, it remains unclear whether this pathway is essential for the energy transfer between carotenoids and chlorophylls. In this work, we performed hybrid quantum mechanics/molecular mechanics simulations with Frenkel exciton models to investigate this energy transfer. The results show that the energy transfer pathways between the S2 state of LUT1 and CLAs are not affected by LUT2 S2. The energy transfer between LUT and chlorophyll-a (CLA) also follows a resonance mechanism. The two LUTs have different energy transfer pathways according to their energy gaps and coupling strengths with each CLA. The present work sheds light on the energy transfer pathways involved in the two LUTs.

9.
Nature ; 624(7992): 630-638, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38093012

ABSTRACT

The COVID-19 pandemic has fostered major advances in vaccination technologies1-4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4-6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.


Subject(s)
COVID-19 Vaccines , Immunity, Mucosal , Animals , Cricetinae , Humans , Mice , Administration, Inhalation , Aerosols , Antibodies, Viral/immunology , Antigen-Presenting Cells/immunology , Antigen-Presenting Cells/metabolism , Antigens, Viral/immunology , Cholera Toxin , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Immunity, Mucosal/immunology , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Nanoparticles , Powders , Primates/virology , SARS-CoV-2/classification , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Vaccination , Capsules
10.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5779-5789, 2023 Nov.
Article in Chinese | MEDLINE | ID: mdl-38114173

ABSTRACT

This study aims to mine the transcription factors that affect the genuineness of Codonopsis pilosula in Shanxi based on the transcriptome data of C. pilosula samples collected from Shanxi and Gansu, and then analyze the gene expression patterns, which will provide a theoretical basis for the molecular assisted breeding of C. pilosula. Gene ontology(GO) functional annotation, conserved motif prediction, and gene expression pattern analysis were performed for the differential transcription factors predicted based on the transcriptome data of C. pilosula from different habitats. A total of 61 differentially expressed genes(DEGs) were screened out from the transcriptome data. Most of the DEGs belonged to AP2/ERF-ERF family, with the conserved motif of [2X]-[LG]-[3X]-T-[3X]-[AARAYDRAA]-[3X]-[RG]-[2X]-A-[2X]-[NFP]. Forty-three of the DEGs showed significantly higher gene expression in C. pilosula samples from Shanxi than in the samples from Gansu, including 11 genes in the AP2/ERF-ERF family, 5 genes in the NAC fa-mily, 1 gene in the bHLH family, and 2 genes in the RWP-RK family, while 18 transcription factors showed higher expression levels in the samples from Gansu. GO annotation predicted that most of the DEGs were enriched in GO terms related to transcriptional binding activity(103), metabolic process(26), and stress response(23). The expression of transcription factor genes, CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 was higher in the samples from Shanxi and in the roots of C. pilosula. CpNAC92, CpbHLH128, and CpRAP2-7 responded to the low temperature, temperature difference, and iron stresses, while CpNAC100 only responded to low temperature and iron stresses. The screening and expression analysis of the specific transcription factors CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 in C. pilosula in Shanxi laid a theoretical foundation for further research on the mechanism of genuineness formation of C. pilosula.


Subject(s)
Codonopsis , Codonopsis/genetics , Codonopsis/chemistry , Transcription Factors/genetics , Gene Expression Profiling , Transcriptome , Iron
11.
PLoS One ; 18(11): e0294363, 2023.
Article in English | MEDLINE | ID: mdl-37971986

ABSTRACT

Valproate (valproic acid, VPA), a drug for the treatment of epilepsy and bipolar disorder, causes liver steatosis with enhanced oxidative stress. Accumulating evidences exhibite that gut microbiota plays an important role in progression of nonalcoholic fatty liver disease (NAFLD). However, whether gut microbiota contributes to VPA-caused hepatic steatosis needs to be elucidated. A mixture of five probiotics was selected to investigate their effects on liver steatosis and oxidative stress in mice orally administered VPA for 30 days. Probiotics treatment significantly attenuated the hepatic lipid accumulation in VPA-treated mice via inhibiting the expression of cluster of differentiation 36 (CD36) and distinct diacylglycerol acyltransferase 2 (DGAT2). Meanwhile, probiotics exerted a protective effect against VPA-induced oxidative stress by decreasing the pro-oxidant cytochrome P450 2E1 (CYP2E1) level and activating the Nrf2/antioxidant enzyme pathway. Moreover, VPA treatment altered the relative abundance of gut microbiota at the phylum, family and genera levels, while probiotics partially restored these changes. Spearman's correlation analysis showed that several specific genera and family were significantly correlated with liver steatosis and oxidative stress-related indicators. These results suggest that probiotics exert their health benefits in the abrogation of liver steatosis and oxidative stress in VPA-treated mice by manipulating the microbial homeostasis.


Subject(s)
Non-alcoholic Fatty Liver Disease , Probiotics , Mice , Animals , Valproic Acid/pharmacology , Valproic Acid/metabolism , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Oxidative Stress , Probiotics/pharmacology , Probiotics/therapeutic use
12.
Neuroimage ; 282: 120400, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37783363

ABSTRACT

Prediction on the partner's speech plays a key role in a smooth conversation. However, previous studies on this issue have been majorly conducted at the single-brain rather than dual-brain level, leaving the interpersonal prediction hypothesis untested. To fill this gap, this study combined a neurocomputational modeling approach with a natural conversation paradigm in which two salespersons persuaded a customer to buy their product with their haemodynamic signals being collected using functional near-infrared spectroscopy hyperscanning. First, the results showed a cognitive hierarchy in a natural conversation, with the lower-level process (i.e., pragmatic representation of the persuasion) in the salesperson interacting with the higher-level process (i.e., value representation of the product) in the customer. Next, we found that the right dorsal lateral prefrontal cortex (rdlPFC) and temporoparietal junction (rTPJ) were associated with the representation of the product's value in the customer, while the right inferior frontal cortex (rIFC) was associated with the representation of the pragmatic processes in the salesperson. Finally, neurocomputational modeling results supported the prediction of the salesperson's lower-level brain activity based on the customer's higher-level brain activity. Moreover, the updating weight of the prediction model based on the neural computation between the rIFC of the salesperson and the rTPJ of the customer was closely associated with the interaction context, whereas that based on the rIFC-rdlPFC was not. In summary, these findings provide initial support for the interpersonal prediction hypothesis at the dual-brain level and reveal a hierarchy for the interpersonal prediction process.


Subject(s)
Brain Mapping , Interpersonal Relations , Humans , Brain Mapping/methods , Brain , Prefrontal Cortex/diagnostic imaging , Frontal Lobe
13.
Phys Chem Chem Phys ; 25(36): 24636-24642, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37665609

ABSTRACT

The energy transfer pathways in light-harvesting complex II are complicated and the discovery of the energy transfer between the two luteins revealed an unelucidated important role of carotenoids in the energy flow. This energy transfer between the two S2 states of luteins was for the first time investigated using Frenkel exciton models, using a hybrid scheme of molecular mechanics and quantum mechanics. The results show the energy flow between the two luteins under the Förster resonance energy transfer mechanism. The energy transfer caused by energy level resonance occurs in configurations with small energy gaps. This energy transfer pathway is particularly sensitive to conformation. Moreover, according to the statistical characteristics of the data of the energy gaps and coupling values between LUTs, we proposed stochastic exciton Hamiltonian models to facilitate clarification of the energy transfer among pigments in antenna complexes.

14.
Adv Mater ; 35(48): e2304956, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37533340

ABSTRACT

Neuroelectrical signals transmitted onto the skin tend to decay to an extremely weak level, making them highly susceptible to interference from the environment and body movement. Meanwhile, for comprehensively understanding cognitive nerve conduction, multimodal sensing of neural signals, such as magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), is highly required. Previous metal or polymer conductors cannot either provide a seamless on-skin feature for accurate sensing of neuroelectrical signals or be compatible with multimodal imaging techniques without opto- and magnet- artifacts. Herein, a ≈20 nm thick MXene film that is able to simultaneously detect electrophysiological signals and perform imaging by MRI and fNIRS with high fidelity is reported. The ultrathin film is made of crosslinked Ti3 C2 Tx film via poly (3,4-ethylene dioxythiophene): polystyrene sulfonate (PEDOT: PSS), showing a record high electroconductivity and transparency combination (11 000 S cm-1 @89%). Among them, PEDOT: PSS not only plays a cross-linking role to stabilize MXene film but also shortens the interlayer distance for effective charge transfer and high transparency. Thus, it can achieve a low interfacial impedance with skin or neural surfaces for accurate recording of electrophysiological signals with low motion artifacts. Besides, the high transparency originating from the ultrathin feature leads to good compatibility with fNIRS and MRI without optical and magnetic artifacts, enabling multimodal cognitive neural monitoring during prolonged use.


Subject(s)
Artifacts , Magnets , Motion , Movement
15.
Biomed Environ Sci ; 36(7): 614-624, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37533385

ABSTRACT

Objective: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. Methods: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. Results: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. Conclusion: Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Humans , Prospective Studies , SARS-CoV-2 , Breakthrough Infections , COVID-19 Vaccines , T-Lymphocytes , China/epidemiology , Antibodies, Viral
16.
Cereb Cortex ; 33(19): 10426-10440, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37562850

ABSTRACT

Although it is well recognized that parent-child shared reading produces positive effects on children's language ability, the underlying neurocognitive mechanisms are not well understood. Here, we addressed this issue by measuring brain activities from mother-child dyads simultaneously during a shared book reading task using functional near infrared spectroscopy hyperscanning. The behavioral results showed that the long-term experience of shared reading significantly predicted children's language ability. Interestingly, the prediction was moderated by children's age: for older children over 30 months, the more the shared reading experience, the better the language performance; for younger children below 30 months, however, no significant relationship was observed. The brain results showed significant interpersonal neural synchronization between mothers and children at the superior temporal cortex, which was closely associated with older children's language ability through the mediation of long-term experience of shared reading. Finally, the results showed that the instantaneous quality of shared reading contributed to children's language ability through enhancing interpersonal neural synchronization and increasing long-term experience. Based on these findings, we tentatively proposed a theoretical model for the relationship among interpersonal neural synchronization, shared reading and children's language ability. These findings will facilitate our understanding on the role of shared reading in children's language development.


Subject(s)
Language Development , Reading , Female , Humans , Child , Adolescent , Child, Preschool , Language , Mothers , Brain
17.
J Alzheimers Dis ; 94(4): 1265-1301, 2023.
Article in English | MEDLINE | ID: mdl-37424469

ABSTRACT

Alzheimer's disease (AD), the most common cause of dementia, is a chronic neurodegenerative disease induced by multiple factors. The high incidence and the aging of the global population make it a growing global health concern with huge implications for individuals and society. The clinical manifestations are progressive cognitive dysfunction and lack of behavioral ability, which not only seriously affect the health and quality of life of the elderly, but also bring a heavy burden to the family and society. Unfortunately, almost all the drugs targeting the classical pathogenesis have not achieved satisfactory clinical effects in the past two decades. Therefore, the present review provides more novel ideas on the complex pathophysiological mechanisms of AD, including classical pathogenesis and a variety of possible pathogenesis that have been proposed in recent years. It will be helpful to find out the key target and the effect pathway of potential drugs and mechanisms for the prevention and treatment of AD. In addition, the common animal models in AD research are outlined and we examine their prospect for the future. Finally, Phase I, II, III, and IV randomized clinical trials or on the market of drugs for AD treatment were searched in online databases (Drug Bank Online 5.0, the U.S. National Library of Medicine, and Alzforum). Therefore, this review may also provide useful information in the research and development of new AD-based drugs.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Animals , Alzheimer Disease/pathology , Quality of Life , Drug Discovery , Models, Animal
18.
Arthritis Res Ther ; 25(1): 117, 2023 07 07.
Article in English | MEDLINE | ID: mdl-37420255

ABSTRACT

BACKGROUND: Intervertebral disc degeneration (IVDD) is closely associated with the structural damage in the annulus fibrosus (AF). Aberrant mechanical loading is an important inducement of annulus fibrosus cells (AFCs) apoptosis, which contributes to the AF structural damage and aggravates IVDD, but the underlying mechanism is still unclear. This study aims to investigate the mechanism of a mechanosensitive ion channel protein Piezo1 in aberrant mechanical loading-induced AFCs apoptosis and IVDD. METHODS: Rats were subjected to lumbar instability surgery to induce the unbalanced dynamic and static forces to establish the lumbar instability model. MRI and histological staining were used to evaluate the IVDD degree. A cyclic mechanical stretch (CMS)-stimulated AFCs apoptosis model was established by a Flexcell system in vitro. Tunel staining, mitochondrial membrane potential (MMP) detection, and flow cytometry were used to evaluate the apoptosis level. The activation of Piezo1 was detected using western blot and calcium fluorescent probes. Chemical activator Yoda1, chemical inhibitor GSMTx4, and a lentiviral shRNA-Piezo1 system (Lv-Piezo1) were utilized to regulate the function of Piezo1. High-throughput RNA sequencing (RNA-seq) was used to explore the mechanism of Piezo1-induced AFCs apoptosis. The Calpain activity and the activation of Calpain2/Bax/Caspase3 axis were evaluated by the Calpain activity kit and western blot with the siRNA-mediated Calapin1 or Calpain2 knockdown. Intradiscal administration of Lv-Piezo1 was utilized to evaluate the therapeutic effect of Piezo1 silencing in IVDD rats. RESULTS: Lumbar instability surgery promoted the expression of Piezo1 in AFCs and stimulated IVDD in rats 4 weeks after surgery. CMS elicited distinct apoptosis of AFCs, with enhanced Piezo1 activation. Yoda1 further promoted CMS-induced apoptosis of AFCs, while GSMTx4 and Lv-Piezo1 exhibited opposite effects. RNA-seq showed that knocking down Piezo1 inhibited the calcium signaling pathway. CMS enhanced Calpain activity and elevated the expression of BAX and cleaved-Caspase3. Calpain2, but not Calpain1 knockdown, inhibited the expression of BAX and cleaved-Caspase3 and alleviated AFCs apoptosis. Lv-Piezo1 significantly alleviated the progress of IVDD in rats after lumbar instability surgery. CONCLUSIONS: Aberrant mechanical loading induces AFCs apoptosis to promote IVDD by activating Piezo1 and downstream Calpain2/BAX/Caspase3 pathway. Piezo1 is expected to be a potential therapeutic target in treating IVDD.


Subject(s)
Annulus Fibrosus , Intervertebral Disc Degeneration , Intervertebral Disc , Animals , Rats , Annulus Fibrosus/metabolism , Annulus Fibrosus/pathology , Apoptosis/genetics , bcl-2-Associated X Protein/metabolism , Calpain , Intervertebral Disc/metabolism , Intervertebral Disc Degeneration/metabolism , Ion Channels/metabolism
19.
World J Clin Cases ; 11(15): 3533-3541, 2023 May 26.
Article in English | MEDLINE | ID: mdl-37383919

ABSTRACT

BACKGROUND: Adult neuronal ceroid lipofuscinosis (ANCL) can be caused by compound heterozygous recessive mutations in CLN6. The main clinical features of the disease are neurodegeneration, progressive motor dysfunction, seizures, cognitive decline, ataxia, vision loss and premature death. CASE SUMMARY: A 37-year-old female presented to our clinic with a 3-year history of limb weakness and gradually experiencing unstable walking. The patient was diagnosed with CLN6 type ANCL after the identification of mutations in the CLN6 gene. The patient was treated with antiepileptic drugs. The patient is under ongoing follow-up. Unfortunately, the patient's condition has deteriorated, and she is currently unable to care for herself. CONCLUSION: There is presently no effective treatment for ANCL. However, early diagnosis and symptomatic treatment are possible.

20.
J Int Med Res ; 51(6): 3000605231183553, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37382236

ABSTRACT

Q fever is an important zoonotic disease caused by the pathogen Coxiella burnetii, which is inhaled into the body through the respiratory tract leading to acute symptoms. Severe acute Q fever may result in complications, such as pneumonia, hepatitis, or myocarditis, and some patients may develop chronic Q fever after incomplete treatment. Local persistent C. burnetii infection may lead to chronic Q fever that often requires surgery and anti-infection treatment for several years, seriously endangering patient health and increasing the economic burden for families. The clinicians' lack of awareness of the disease may be one reason leading to a delay in treatment. Here, a case of Q fever in a 53-year-old male patient, which was diagnosed by next generation sequencing and exhibited a distinct computed tomographic feature, is reported, with the aim of improving clinical knowledge of this disease. Following diagnosis, the patient was treated with 0.1 g doxycycline, orally, twice daily, and 0.5 g chloramphenicol, orally, three times daily, leading to improvement of symptoms and discharge from hospital.


Subject(s)
Multiple Pulmonary Nodules , Q Fever , Male , Animals , Humans , Middle Aged , Q Fever/complications , Q Fever/diagnosis , Q Fever/drug therapy , Zoonoses , Chloramphenicol , Doxycycline/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...