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1.
Gene ; 850: 146932, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36191827

RESUMO

High mobility group box 1 (HMGB1) and high mobility group box 2 (HMGB2) were highly conserved nonhistone chromosomal proteins involved in DNA damage repair, innate immune and inflammatory response. In this study, Acipenser baerii HMGB1 (AbHMGB1) and HMGB 2 (AbHMGB2) were identified. The open reading frame (ORF) of AbHMGB1 was 621 bp which encoded 206 amino acids, and the ORF of AbHMGB2 was 630 bp encoded 209 amino acids. AbHMGB1 and AbHMGB2 were conserved compared with bony fish by phylogenetic analyzing. qRT-PCR showed that AbHMGB1 and AbHMGB2 were expressed in all examined tissues, AbHMGB1 was expressed abundantly in muscle, followed by head kidney and brain, and AbHMGB2 was highest expressed in gill, followed by brain and muscle. After Streptococcus iniae infection and PAMPs treatment, AbHMGB1 and AbHMGB2 were induced significantly. This study indicated that AbHMGB1 and AbHMGB2 are involved in the process of pathogenic infection and provided a basis for exploring the mechanism of Acipenser baerii enteritis induced by Streptococcus iniae.


Assuntos
Proteína HMGB1 , Infecções Estreptocócicas , Animais , Proteína HMGB2/genética , Proteína HMGB2/metabolismo , Filogenia , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Padrões Moleculares Associados a Patógenos , Peixes/metabolismo , Aminoácidos/genética
2.
Tour Manag ; 94: 104658, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36119661

RESUMO

The COVID-19 pandemic has placed the notion of "travel shaming" under the spotlight-tourists are concerned about being criticized for traveling during the pandemic. Yet the broader idea of travel-induced shaming, conceptualized as ethics-based evaluations in this paper, has not drawn much attention as consequence-based assessments in travel-related risk research. This paper presents two studies revealing a) how ethics- and consequence-based risk evaluations influence individuals' travel attitudes/intentions and b) how message framing about responsible travel affects travel shame and individuals' intentions to travel responsibly. Using structural equation modeling, Study 1 suggests that consequence- and ethics-based evaluations play key roles in predicting travelers' attitudes/intentions to travel. Moreover, social trust and self-efficacy significantly affect both types of risk evaluations. Study 2 adopts an experimental design and shows that, compared with loss-framed and controlled message conditions, gain-framed messaging can reduce travel shame and encourage tourists to travel responsibly. Theoretical and practical implications were discussed.

3.
J Affect Disord ; 320: 305-312, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36174786

RESUMO

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) benefits adults with depression while its efficacy and safety in children and adolescents with major depressive disorder (MDD) remain unclear. We conducted a preliminary meta-analysis here to objectively appraise rTMS in the youth with MDD to inform future research and clinical practice. METHODS: We searched Pubmed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials from their inception to December 1, 2021. Studies with a control group or self-controlled designs and evaluating the Hamilton Depression Scale (HAM-D) or the Children's Depression Rating Scale-Revised (CDRS-R) at baseline and post-rTMS treatment were included. Two reviewers independently selected eligible studies, retrieved data in a structured fashion and assessed studies' quality. Hedges'g with 95 % confidence intervals and withdrawal rate with 95 % confidential intervals were separately used to evaluate the efficacy and safety of rTMS. RESULTS: Thirteen studies with six datasets (165 patients, 61.8 % female, age range from 10 to 25 years old) were included and our meta-analysis found children and adolescents with MDD benefited from rTMS treatment (Hedges'g 1.37, 95 % CI 0.85 to 1.90, P = 0.001). In addition, 4 % of patients (95 % CI 0.02 to 0.09) withdrew during rTMS treatment for reasons including fear, mood swings, suicide ideation and adverse events. LIMITATIONS: This conclusion is tempered by a small number of studies included and a potentially existing placebo effect. CONCLUSIONS: Our findings suggest rTMS could benefit children and adolescents with MDD in a relatively safe manner, and this result may help guide clinical practice.


Assuntos
Transtorno Depressivo Maior , Estimulação Magnética Transcraniana , Humanos , Adolescente , Adulto , Criança , Feminino , Adulto Jovem , Masculino , Estimulação Magnética Transcraniana/efeitos adversos , Transtorno Depressivo Maior/terapia , Depressão , Efeito Placebo , Transtornos do Humor , Resultado do Tratamento
4.
Animal Model Exp Med ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376997

RESUMO

BACKGROUND: Gastrointestinal (GI) injury is one of the most common side effects of radiotherapy. However, there is no ideal therapy method except for symptomatic treatment in the clinic. Xuebijing (XBJ) is a traditional Chinese medicine, used to treat sepsis by injection. In this study, the protective effects of XBJ on radiation-induced intestinal injury (RIII) and its mechanism were explored. METHODS: The effect of XBJ on survival of irradiated C57BL/6 mice was monitored. Histological changes including the number of crypts and the length of villi were evaluated by H&E. The expression of Lgr5+ intestinal stem cells (ISCs), Ki67+ cells, villin and lysozymes were examined by immunohistochemistry. The expression of cytokines in the intestinal crypt was detected by RT-PCR. DNA damage and apoptosis rates in the small intestine were also evaluated by immunofluorescence. RESULTS: In the present study, XBJ improved the survival rate of the mice after 8.0 and 9.0 Gy total body irradiation (TBI). XBJ attenuated structural damage of the small intestine, maintained regenerative ability and promoted proliferation and differentiation of crypt cells, decreased apoptosis rate and reduced DNA damage in the intestine. Elevation of IL-6 and TNF-α was limited, but IL-1, TNF-𝛽 and IL-10 levels were increased in XBJ-treated group after irradiation. The expression of Bax and p53 were decreased after XBJ treatment. CONCLUSIONS: Taken together, XBJ provides a protective effect on RIII by inhibiting inflammation and blocking p53-related apoptosis pathway.

5.
Phytother Res ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36349468

RESUMO

Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.

6.
Infect Drug Resist ; 15: 6613-6623, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386421

RESUMO

Background: Severe complications may cause a fatal or disabling outcome in patients with Rickettsia japonica infection but are poorly understood. Methods: We identified 11 patients with only Rickettsia japonica infection with metagenomics next generation sequencing (mNGS) during April to November 2021 at Yichang Central People's Hospital, China. Clinical data were obtained through review of medical records. Results: Most patients realized that they had symptoms about one or two days after being bitten. Fever (91%), pulmonary effusion (91%), rash or erythema (100%), abnormal urine (100%), neutropenia (100%), lymphopenia (100%), and thrombocytopenia (100%) were the most common clinical signs. Six severely ill patients were admitted to the intensive care unit and five had mild symptoms. Systemic manifestations such as vomiting (83%), neurological manifestations (100%), and disseminated intravascular coagulation (100%) were more frequently observed in the severe cases, 33.3% of whom developed purpura fulminans requiring amputation or skin graft, and 16.6% died two days after admission. Some patients experienced sequelae. Conclusion: Our study found that patients with critical Rickettsia japonica infection complicating disseminated intravascular coagulation had high risk of poor outcome.

7.
J Clin Lab Anal ; : e24765, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397297

RESUMO

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by unifocal, multifocal single-system, or multi-system disease that occurs in all age groups, while it primarily attacks pediatric patients. Solitary gastrointestinal (GI) LCH in adults is exceedingly rare, so we aimed to investigate GI LCH in adults with unifocal single-system involvement and clarified the clinicopathologic characteristics of this disease. METHODS: Two cases of solitary GI LCH in adults were presented, and the clinicopathologic features of this diagnosis in the literature were reviewed. RESULTS: The main diagnostic feature of LCH is the morphologic identification of the characteristic Langerhans cells with prominent nuclear grooves and abundant eosinophilic cytoplasm, accompanied by a variable number of lymphocytes, eosinophils, and plasma cells. The distinctive cells expressed S100, CD1a, and langerin (CD207) on immunohistochemistry. BRAF V600E mutations were detected in the two patients. CONCLUSIONS: Gastrointestinal Langerhans cell histiocytosis in adults with unifocal, single-system involvement is extremely rare. Most patients were asymptomatic and usually a small solitary polyp in GI tract can be observed under routine endoscopy. Although the overall prognosis of unifocal single-system LCH is favorable, long-term follow-up is still necessary to rule out systemic disease.

8.
Cell Stem Cell ; 29(11): 1594-1610.e8, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36332572

RESUMO

The molecular diversity of glia in the human hippocampus and their temporal dynamics over the lifespan remain largely unknown. Here, we performed single-nucleus RNA sequencing to generate a transcriptome atlas of the human hippocampus across the postnatal lifespan. Detailed analyses of astrocytes, oligodendrocyte lineages, and microglia identified subpopulations with distinct molecular signatures and revealed their association with specific physiological functions, age-dependent changes in abundance, and disease relevance. We further characterized spatiotemporal heterogeneity of GFAP-enriched astrocyte subpopulations in the hippocampal formation using immunohistology. Leveraging glial subpopulation classifications as a reference map, we revealed the diversity of glia differentiated from human pluripotent stem cells and identified dysregulated genes and pathological processes in specific glial subpopulations in Alzheimer's disease (AD). Together, our study significantly extends our understanding of human glial diversity, population dynamics across the postnatal lifespan, and dysregulation in AD and provides a reference atlas for stem-cell-based glial differentiation.


Assuntos
Doença de Alzheimer , Transcriptoma , Humanos , Transcriptoma/genética , Longevidade/genética , Neuroglia/patologia , Hipocampo , Astrócitos/patologia , Doença de Alzheimer/patologia
9.
ACS Appl Mater Interfaces ; 14(45): 50485-50498, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36331130

RESUMO

Current artificial periostea mainly focus on osteogenic activity but overlook structural and mechanical anisotropy, as well as the importance of antibacterial and anti-inflammatory properties. Here, inspired by the anisotropic structure of wood, the delignified wood (named white wood, WW) with a porous and highly oriented cellulose fiber skeleton was obtained, which was further filled with polyvinyl alcohol (PVA) hydrogel loaded with curcumin (Cur) and phytic acid (PA). The prepared wood-derived hydrogel composite membranes can not only exhibit an obvious anisotropic structure and good mechanical properties but also sustainably release loaded drugs to obtain long-term biological activities. Creatively, PA can effectively improve the bioavailability of Cur; more importantly, Cur and PA play an obvious synergistic effect in antibacterial, anti-inflammatory, and osteogenic activities. Compared with the wood-derived hydrogel composite membranes without drug loading, as well as loaded with Cur or PA only, these loaded with Cur and PA are significantly more conducive to inhibiting the growth of bacteria and inflammatory response and facilitating the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells. This kind of anisotropic wood-derived hydrogel composite membrane with fantastic antibacterial, anti-inflammatory, and osteogenic activities is expected to be ideal artificial periostea.


Assuntos
Curcumina , Hidrogéis , Hidrogéis/farmacologia , Hidrogéis/química , Osteogênese , Periósteo , Anisotropia , Madeira , Antibacterianos/farmacologia , Antibacterianos/química , Curcumina/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
11.
Fish Shellfish Immunol ; 131: 697-706, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36341872

RESUMO

Natural plant polysaccharide as immune modulator is considered an effective strategy for healthy aquaculture to reduce medicine treatment. Salvia miltiorrhiza polysaccharides (SMP) had applications to regulate immune activity and enhance antioxidant in vertebrates, but the potential function has been rarely reported in crustaceans. In this study, the immunological effects of SMP on hemocytes of Procambarus clarkii were analyzed. Results showed that total superoxide dismutase (T-SOD), phenoloxidase (PO) activity and respiratory burst were up-regulated after SMP treatment. After high-throughput sequencing, 2170 differentially expressed genes (DEGs) including 1294 up-regulated and 876 down-regulated genes were identified. KEGG function enrichment analysis indicated that DEGs are involved in crustaceans cellular immune-related signaling pathways, including lysosome, phagosome and endocytosis. Transcriptome mining and qRT-PCR showed that SMP up-regulated humoral immunity factors gene expression. Diets supplemented with 0.8% SMP significantly up-regulated the total number of hemocytes (THC), T-SOD and PO activity, improved the survival of crayfish after Citrobacter freundii infection. This study suggested that SMP could improve the cellular and humoral immunity of P. clarkii. Furthermore, this finding supplied a molecular foundation for further comprehending the immunopotentiator effects of plant polysaccharides in crustaceans.

12.
Commun Biol ; 5(1): 1179, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333470

RESUMO

Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-α-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against α-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs.


Assuntos
COVID-19 , Coronavirus Humano 229E , Humanos , Glicoproteína da Espícula de Coronavírus/genética , SARS-CoV-2 , Antígenos Virais , Epitopos , Anticorpos Neutralizantes
13.
Commun Biol ; 5(1): 1184, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333580

RESUMO

A precise understanding of amygdala-centered subtle networks may help refine neurocircuitry models of obsessive-compulsive disorder (OCD). We applied connectivity-based parcellation methodology to segment the amygdala based on resting-state fMRI data of 92 medication-free OCD patients without comorbidity and 90 matched healthy controls (HC). The amygdala was parcellated into two subregions corresponding to basolateral amygdala (BLA) and centromedial amygdala (CMA). Amygdala subregional functional connectivity (FC) maps were generated and group differences were evaluated with diagnosis-by-subregion flexible factorial ANOVA. We found significant diagnosis × subregion FC interactions in insula, supplementary motor area (SMA), midcingulate cortex (MCC), superior temporal gyrus (STG) and postcentral gyrus (PCG). In HC, the BLA demonstrated stronger connectivity with above regions compared to CMA, whereas in OCD, the connectivity pattern reversed to stronger CMA connectivity comparing to BLA. Relative to HC, OCD patients exhibited hypoconnectivity between left BLA and left insula, and hyperconnectivity between right CMA and SMA, MCC, insula, STG, and PCG. Moreover, OCD patients showed reduced volume of left BLA and right CMA compared to HC. Our findings characterized disorganized functional architecture of amygdala subregional networks in accordance with structural defects, providing direct evidence regarding the specific role of amygdala subregions in the neurocircuitry models of OCD.


Assuntos
Mapeamento Encefálico , Transtorno Obsessivo-Compulsivo , Humanos , Vias Neurais , Tonsila do Cerebelo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
14.
World J Clin Cases ; 10(31): 11427-11441, 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36387814

RESUMO

BACKGROUND: Postoperative gastrointestinal function recovery is critical for rapid rehabilitation of patients with gastrointestinal tumors. Traditional Chinese medicine offers considerable advantages for gastrointestinal disease treatment. However, no study has reported the clinical efficacy of intradermal needle therapy (INT) at the Yuan-source, Luo-connecting, and He-sea points of the corresponding meridian for gastrointestinal function in patients following surgery for gastrointestinal tumors. AIM: To investigate the effect of INT at combined acupoints on patients' gastrointestinal function following surgery for gastrointestinal tumors. METHODS: This randomized controlled trial was conducted at the Second Affiliated Hospital of Xi'an Jiaotong University on patients with diagnosed gastrointestinal cancer, no distant metastases or organ failure, and hospitalized for elective radical tumor resection, who did not receive preoperative radiotherapy or chemotherapy. Participants were randomly allocated to either the intervention (n = 32) or the control (n = 32) group. Participants in the control group received enhanced recovery care, while those in the intervention group received enhanced recovery care combined with INT at the Yuan-source, Luo-connecting, and He-sea points. After surgery, INT was performed immediately upon the patient's return to the ward, and continued for seven consecutive days. The independent samples t-test, chi-square test, and generalized estimating equations were used for data analysis. RESULTS: The participants' ages ranged from 40 to 80 years (average 63 ± 10.1 years). Most participants underwent surgery for either gastric (43.8%) or colon cancer (39.1%) and had adenocarcinoma (87.5%). Significant differences were noted in time to first postoperative flatus passage (66 ± 27 h vs 103 ± 41 h, P < 0.001), time to first defecation (106 ± 44 h vs 153 ± 50 h, P < 0.001), and time to first oral feeding (73 ± 30 h vs 115 ± 38 h, P < 0.001) between the intervention and control groups. Gastrointestinal symptoms, including abdominal distension, nausea, and fatigue 48 h and 72 h after surgery, were significantly alleviated in the intervention group compared with that observed in the control group (P < 0.05). CONCLUSION: INT at the Yuan-source, Luo-connecting, and He-sea points can promote recovery of gastrointestinal function and ease gastrointestinal symptoms in patients following surgical resection of gastrointestinal tumors.

16.
J Am Chem Soc ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416791

RESUMO

Herein, we demonstrate the successful utilization of reticular chemistry as an excellent designing strategy for the deliberate construction of a zirconium-tetracarboxylate metal-organic framework (MOF) inspired by the Olympic rings. HIAM-4017, with an unprecedented (4,8)-c underlying net topology termed jcs, was developed via insightful reconstruction of the rings and judicious design of a nonsymmetric organic linker. HIAM-4017 exhibits high porosity and excellent chemical and thermal stability. Furthermore, excited-state intramolecular proton transfer (ESIPT) was achieved in an isoreticular MOF, HIAM-4018, with a large Stokes shift of 155 nm as a result of introducing the hydroxyl group to the linker skeleton to induce OH···N interactions. Such interactions were analyzed thoroughly by employing the time-dependent density functional theory (TD-DFT). Because of their good thermal and chemical stability, and strong luminescence, nanosized HIAM-4017 and HIAM-4018 were fabricated and used for Cr2O72- detection. Both MOFs demonstrate excellent sensitivity and selectivity. This work represents a neat example of building structure- and property-specific MOFs guided by reticular chemistry.

17.
Radiother Oncol ; 177: 185-190, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36375560

RESUMO

PURPOSE: Whether cervical lymph node necrosis (CNN) is an independent adverse prognostic factor in nasopharyngeal carcinoma (NPC) has not been determined. In this study, the CNN ratio was graded quantitatively to explore the prognostic value in NPC. PARTICIPANTS AND METHODS: We retrospectively reviewed a total of 648 pathologically confirmed as NPC. We outlined metastatic lymph nodes and necrotic area of lymph nodes slice by slice on the magneticresonanceimages (MRI) cross section, and calculated the corresponding CNN ratio. RESULTS: The median CNN ratio (17.37 %) was taken as the cut-off point, 256 (39.51 %) patients were divided into CNN1 group (<17.37 %, n = 128) and CNN2 group (≥17.37 %, n = 128), 392 (60.49 %) patients without lymph nodes necrosis were CNN0. Among the CNN0, CNN1 and CNN2 groups, five-year overall survival (OS) was 82.4 %, 76.6 % and 71.1 %, locoregional recurrence-free survival (LRRFS) was 91.3 %, 91.1 % and 90.5 %, distant metastasis-free survival (DMFS) was 83.7 %, 78.5 % and 68.7 %, progression-free survival (PFS) was 78.3 %, 71.7 % and 61.6 % respectively. By multivariate analysis, CNN was an independent prognostic factor for OS (P = 0.003), DMFS (P = 0.019) and PFS (P = 0.007). More than 3 cycles of chemotherapy significantly increased OS (P = 0.024) and DMFS (P = 0.015) in the CNN1 group. CONCLUSIONS: This study indicated that CNN is one of the factors with the negative prognosis of NPC. The CNN ratio might be used as one of the reference factors in the formulation of individualized treatment plan.

18.
Front Bioeng Biotechnol ; 10: 1043939, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406213

RESUMO

The efficacy of treating solid tumors with chemotherapy is primarily hindered by dose-limiting toxicity due to off-target effects and the heterogeneous drug distribution caused by the dense extracellular matrix. The enhanced permeability and retention (EPR) effect within tumors restricts the circulation and diffusion of drugs. To overcome these obstacles, hydrogels formed in situ at the tumor site have been proposed to promote drug accumulation, retention, and long-lasting release. We developed a thiolated chitosan (CSSH) hydrogel with a gelation point of 37°C. Due to the pH-sensitive characteristics of disulfides, the prepared hydrogel facilitated drug release in the acidic tumor environment. A drug release system composed of hydrophilic doxorubicin (Dox) and hydrophobic liposome-encapsulated curcumin (Cur-Lip) was designed to enhance the long-lasting therapeutic impacts and reduce adverse side effects. These composite gels possess a suitable gelation time of approximately 8-12 min under physiological conditions. The cumulative release ratio was higher at pH = 5.5 than at pH = 7.4 over the first 24 h, during which approximately 10% of the Dox was released, and Cur was released slowly over the following 24-120 h. Cell assays indicated that the Cur-Lip/Dox/CSSH gels effectively inhibited the growth of cancer cells. These in situ-formed Cur-Lip/Dox gels with long-term drug release capabilities have potential applications for tumor suppression and tissue regeneration after surgical tumor resection.

19.
Neural Plast ; 2022: 3995227, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406589

RESUMO

Voltage-gated sodium channel beta 2 (Nav2.2 or Navß2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navß2 in amyloid-ß 1-42- (Aß1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navß2 knockdown restored neuronal viability of Aß1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aß42, sAPPα, and sAPPß, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aß degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navß2 plays crucial roles in the repair of neuronal injury induced by Aß1-42 both in vivo and in vitro.


Assuntos
Disfunção Cognitiva , Canais de Sódio Disparados por Voltagem , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Neurônios/metabolismo , Canais de Sódio Disparados por Voltagem/metabolismo , Neprilisina/genética , Neprilisina/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo
20.
J Alzheimers Dis Rep ; 6(1): 557-575, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275418

RESUMO

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disease affecting many cellular pathways, including protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation. Currently, no effective treatment for AD exists. Objective: We aim to determine the effect of lithium benzoate (LiBen) in protecting neurons from amyloid-ß (Aß) or other neurotoxin insults. Methods: Primary rat cortical neurons co-treated with neurotoxins and LiBen were used to examine its effect in cell viability, reactive oxygen species (ROS) clearance, and mitochondrial functions by MTT, CellRox fluorescence staining, and seahorse assay. Then, Barnes maze and prepulse inhibition test were performed in APP/PS1 mice that received chronic LiBen treatment to assess its effect on cognitive protection. Oral bioavailability of LiBen was also assessed by pharmacokinetic study in rat plasma. Results: In this study, we discovered that LiBen can attenuate cellular ROS level, improve mitochondrial function, increase cell viability against multiple different insults of mitochondrial dysfunction, Aß accumulation, and neuroinflammation, and promote neurogenesis. We demonstrated that LiBen has advantages over lithium or sodium benzoate alone as LiBen displays superior neuroprotective efficacy and oral bioavailability than the other two agents when being applied either alone or in combination. Furthermore, chronic administration of LiBen showed protection for cognition as well as spatial memory and reduced the senile plaque deposition in brains of AD animal models. Conclusion: LiBen stands as a promising therapeutic agent for improving cognition and delaying the progression of AD.

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