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1.
FASEB J ; 38(10): e23655, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38767449

RESUMO

The disruption of mitochondria homeostasis can impair the contractile function of cardiomyocytes, leading to cardiac dysfunction and an increased risk of heart failure. This study introduces a pioneering therapeutic strategy employing mitochondria derived from human umbilical cord mesenchymal stem cells (hu-MSC) (MSC-Mito) for heart failure treatment. Initially, we isolated MSC-Mito, confirming their functionality. Subsequently, we monitored the process of single mitochondria transplantation into recipient cells and observed a time-dependent uptake of mitochondria in vivo. Evidence of human-specific mitochondrial DNA (mtDNA) in murine cardiomyocytes was observed after MSC-Mito transplantation. Employing a doxorubicin (DOX)-induced heart failure model, we demonstrated that MSC-Mito transplantation could safeguard cardiac function and avert cardiomyocyte apoptosis, indicating metabolic compatibility between hu-MSC-derived mitochondria and recipient mitochondria. Finally, through RNA sequencing and validation experiments, we discovered that MSC-Mito transplantation potentially exerted cardioprotection by reinstating ATP production and curtailing AMPKα-mTOR-mediated excessive autophagy.


Assuntos
Proteínas Quinases Ativadas por AMP , Apoptose , Autofagia , Células-Tronco Mesenquimais , Mitocôndrias , Miócitos Cardíacos , Serina-Treonina Quinases TOR , Miócitos Cardíacos/metabolismo , Animais , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Camundongos , Humanos , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/metabolismo , Masculino , Doxorrubicina/farmacologia , Camundongos Endogâmicos C57BL , Insuficiência Cardíaca/metabolismo
2.
PLoS One ; 19(5): e0303557, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38771840

RESUMO

BACKGROUND: Urinary tract infections (UTI) is a prevalent condition in those with diabetes, and in severe cases, it may escalate to sepsis. Therefore, it is important to analyze the risk variables associated with sepsis in diabetes individuals with UTI. METHODS: This research was a retrospective cross-sectional analysis. From January 2011 to June 2022, a group of individuals with diabetes were identified as having UTI at a tertiary hospital situated in Southeastern China. Patient data, including information on urine culture, was collected retrospectively from a clinical record database. The participants were categorized into the sepsis and non-sepsis groups. The risk variables were derived using both uni-and multiple- variable regression analysis. RESULTS: The research included 1919 patients, of whom 1106 cases (57.63%) had positive urine cultures. In total, 445 blood culture samples were tested, identifying 186 positive cases (41.80%). The prevalence of bacteria in urine and blood samples was highest for Escherichia coli and Klebsiella pneumoniae, respectively. Moreover, 268 individuals (13.97%) exhibited sepsis. The regression analysis indicated a positive correlation between sepsis and albumin (ALB)<34.35 g/L, C-reactive protein (CRP)>55.84 mg/L and white blood cell count (WBC) >8.485 X 109/L in diabetic cases with UTIs. By integrating the three aforementioned parameters, the area under the receiver operating characteristic curve was 0.809. CONCLUSIONS: The early detection of sepsis in diabetic individuals with UTI may be achieved using a comprehensive analysis of CRP, WBC, and ALB test findings.


Assuntos
Sepse , Infecções Urinárias , Humanos , Infecções Urinárias/complicações , Infecções Urinárias/microbiologia , Infecções Urinárias/epidemiologia , Masculino , Feminino , Sepse/complicações , Sepse/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Estudos Transversais , Fatores de Risco , China/epidemiologia , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Diabetes Mellitus/epidemiologia , Adulto , Klebsiella pneumoniae/isolamento & purificação , Contagem de Leucócitos , Complicações do Diabetes/microbiologia , Complicações do Diabetes/epidemiologia
3.
Eur J Clin Nutr ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467857

RESUMO

The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis BLa80, as an adjunct treatment for diarrhea in children with a randomized, double-blinded, placebo-controlled study design. Eligible diarrheal children, aged 0-3 years without the need for antibiotic treatment based on clinical diagnosis when recruited, were randomized into the intervention group (IG, n = 58, with probiotic) or the control group (CG, n = 53, placebo). The primary assessment was the duration of diarrhea. Fecal samples were collected for biochemical index measurement, analysis of gut microbiome composition, and prediction of gene family abundances. The total duration of diarrhea in the IG (122.6 ± 13.1 h) was significantly shorter than in the CG (148.4 ± 17.6 h, p < 0.001). More children in the IG showed improvements in diarrhea compared to the CG, both in intention-to-treat analysis (81.7% vs. 40.0%, p < 0.001) and per protocol analysis (84.4% vs 45.3%, p < 0.001). Cathelicidin level in the IG was significantly higher than that in the CG after the intervention (4415.00 ± 1036.93 pg/g vs. 3679.49 ± 871.18 pg/g, p = 0.0175). The intervention led to an increased abundance of Bifidobacterium breve and Collinsella aerofaciens species, higher alpha-diversity (p < 0.05), and enrichment of functional genes in the gut microbiota related to immunity regulation. Administration of BLa80 at a dose of 5 × 109 CFU/day resulted in a shorter duration of diarrhea and alterations in gut microbiome composition and gene functions.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38477044

RESUMO

Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.

5.
Adv Healthc Mater ; 13(13): e2303674, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38315148

RESUMO

Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity-reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC-derived exosomes (DSC-exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal-to-epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC-exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.


Assuntos
Alginatos , Endométrio , Exossomos , Hidrogéis , Regeneração , Células Estromais , Feminino , Alginatos/química , Exossomos/metabolismo , Exossomos/química , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Endométrio/citologia , Endométrio/metabolismo , Camundongos , Regeneração/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/citologia , Decídua/citologia , Decídua/metabolismo , Fertilidade/fisiologia , MicroRNAs/metabolismo , MicroRNAs/genética , Humanos , Aderências Teciduais/metabolismo
6.
Expert Opin Drug Deliv ; 21(2): 347-363, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38406829

RESUMO

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are evolving as a prominent determinant in cancer occurrence and development and are functionally found to suppress T cells in cancer. Not much research is done regarding its involvement in viral infections. This research was designed to investigate the role of MDSCs in hepatitis B virus (HBV) infection and how targeting these cells with our novel all-trans retinoic acid encapsulated liposomal formulation could improve immunotherapy in C57BL/6 mice. METHODS: Ten micrograms (10 µg) of plasmid adeno-associated virus (pAAV/HBV 1.2, genotype A) was injected hydrodynamically via the tail vein of C57BL/6 mice. An all-trans retinoic acid encapsulated liposomal formulation (L-ATRA) with sustained release properties was used in combination with tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor (nRTI) to treat the HBV infection. The L-ATRA formulation was given at a dose of 5 mg/kg intravenously (IV) twice a week. The TDF was given orally at 30 mg/kg daily. RESULTS: Our results revealed that L-ATRA suppresses MDSCs in HBV infected mice and enhanced T-cell proliferation in vitro. In vivo studies showed higher and improved immunotherapeutic effect in mice that received L-ATRA and TDF concurrently in comparison with the groups that received monotherapy. Lower HBV DNA copies, lower concentrations of HBsAg and HBeAg, lower levels of ALT and AST and less liver damage were seen in the mice that received the combination therapy of L-ATRA + TDF. CONCLUSIONS: In effect, targeting MDSCs with the combination of L-ATRA and TDF effectively reduced mMDSC and improved immunotherapy in the HBV infected mice. Targeting MDSCs could provide a breakthrough in the fight against hepatitis B virus infection.


Assuntos
Hepatite B Crônica , Hepatite B , Células Supressoras Mieloides , Neoplasias , Animais , Camundongos , Vírus da Hepatite B/genética , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Antígenos E da Hepatite B/farmacologia , Antígenos E da Hepatite B/uso terapêutico , Resultado do Tratamento , Camundongos Endogâmicos C57BL , Tenofovir/farmacologia , Tenofovir/uso terapêutico , Hepatite B/tratamento farmacológico , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Neoplasias/tratamento farmacológico
7.
Braz J Microbiol ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381349

RESUMO

Functional constipation (FC) can seriously affect the physical and mental health of children. The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis XLTG11 in treating FC in children through a randomized, double-blinded, placebo-controlled approach. Eligible children were randomized into either the intervention group (IG, n = 65, receiving conventional treatment with probiotics) or the control group (CG, n = 66, receiving conventional treatment without probiotics). The primary outcome measure was fecal frequency. Fecal gut microbiota analysis and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) were used to predict gene family abundances based on 16S information. Over the course of treatment, the weekly frequency of feces within each group increased significantly (F = 41.97, p < 0.001). The frequency of feces (times/week (t/w)) in the IG was significantly higher than that in the CG (3.69 ± 2.62 t/w vs.3.18 ± 1.43 t/w, 4.03 ± 2.54 t/w vs. 2.89 ± 1.39 t/w and 3.74 ± 2.36 t/w vs. 2.94 ± 1.18 t/w and 3.45 ± 1.98 vs. 3.17 ± 1.41 t/w for the 1st, 2nd, 3rd, and 4th week after intervention, respectively) (F = 7.60, p = 0.0067). After the intervention, dominate species shifted to Bifidobacterium longum, Bifidobacterium breve, and Escherichia coli in the IG. Additionally, genes related to short-chain fatty acid (SCF) metabolism were upregulated, while methane metabolism was downregulated. Administration of XLTG11 at a dose of 1 × 1010 CFU/day to children increased fecal frequency, induced beneficial changes in gut microbiota, and regulated SCFs and methane metabolism-related genes.

8.
Curr Top Med Chem ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38333981

RESUMO

Osteoporosis and other bone diseases are a major public health concern worldwide. Current pharmaceutical treatments for bone disorders have limitations, driving interest in complementary herbal medicines that can help maintain bone health. This review summarizes the scientific evidence for medicinal herbs that modulate bone cell activity and improve bone mass, quality and strength. Herbs with osteogenic, anti-osteoporotic, and anti-osteoclastic effects are discussed, including compounds and mechanisms of action. Additionally, this review examines the challenges and future directions for translational research on herbal medicines for osteoporosis and bone health. While preliminary research indicates beneficial bone bioactivities for various herbs, rigorous clinical trials are still needed to verify therapeutic efficacy and safety. Further studies should also elucidate synergistic combinations, bioavailability of active phytochemicals, and precision approaches to match optimal herbs with specific etiologies of bone disease. Advancing evidence- based herbal medicines may provide novel alternatives for promoting bone homeostasis and treating skeletal disorders.

9.
Transl Vis Sci Technol ; 13(1): 2, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38165718

RESUMO

Purpose: This study aimed to investigate the association between quantitative retinal vascular measurements and the risk of all-cause and premature mortality. Methods: In this population-based cohort study using the UK Biobank data, we employed the Retina-based Microvascular Health Assessment System to assess fundus images for image quality and extracted 392 retinal vascular measurements per fundus image. These measurements encompass six categories of vascular features: caliber, density, length, tortuosity, branching angle, and complexity. Univariate Cox regression models were used to identify potential indicators of mortality risk using data on all-cause and premature mortality from death registries. Multivariate Cox regression models were then used to test these associations while controlling for confounding factors. Results: The final analysis included 66,415 participants. After adjusting for demographic, health, and lifestyle factors and genetic risk score, 18 and 10 retinal vascular measurements were significantly associated with all-cause mortality and premature mortality, respectively. In the fully adjusted model, the following measurements of different vascular features were significantly associated with all-cause mortality and premature mortality: arterial bifurcation density (branching angle), number of arterial segments (complexity), interquartile range and median absolute deviation of arterial curve angle (tortuosity), mean and median values of mean pixel widths of all arterial segments in each image (caliber), skeleton density of arteries in macular area (density), and minimum venular arc length (length). Conclusions: The study revealed 18 retinal vascular measurements significantly associated with all-cause mortality and 10 associated with premature mortality. Those identified parameters should be further studied for biological mechanisms connecting them to increased mortality risk. Translational Relevance: This study identifies retinal biomarkers for increased mortality risk and provides novel targets for investigating the underlying biological mechanisms.


Assuntos
Vasos Retinianos , Biobanco do Reino Unido , Humanos , Vasos Retinianos/diagnóstico por imagem , Estudos de Coortes , Bancos de Espécimes Biológicos , Retina/diagnóstico por imagem
10.
Int J Oral Sci ; 16(1): 3, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38221531

RESUMO

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.


Assuntos
Piroptose , Técnicas de Movimentação Dentária , Animais , Humanos , Camundongos , Ratos , Remodelação Óssea/fisiologia , Caspase 1 , Ligamento Periodontal
11.
Acta Biochim Biophys Sin (Shanghai) ; 56(1): 23-33, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38062774

RESUMO

Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure, primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates Src/PI3K/ERK signaling, thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.


Assuntos
Melatonina , Defeitos do Tubo Neural , Gravidez , Feminino , Criança , Humanos , Ácido Valproico , Melatonina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/prevenção & controle , Estresse Oxidativo , Transdução de Sinais
12.
Plant Physiol ; 194(2): 884-901, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37944026

RESUMO

A reliable and stable hydrogen gas (H2) supply will benefit agricultural laboratory and field trials. Here, we assessed ammonia borane (AB), an efficient hydrogen storage material used in the energy industry, and determined its effect on plant physiology and the corresponding mechanism. Through hydroponics and pot experiments, we discovered that AB increases tomato (Solanum lycopersicum) lateral root (LR) branching and this function depended on the increased endogenous H2 level caused by the sustainable H2 supply. In particular, AB might trigger LR primordia initiation. Transgenic tomato and Arabidopsis (Arabidopsis thaliana) expressing hydrogenase1 (CrHYD1) from Chlamydomonas reinhardtii not only accumulated higher endogenous H2 and phytomelatonin levels but also displayed pronounced LR branching. These endogenous H2 responses achieved by AB or genetic manipulation were sensitive to the pharmacological removal of phytomelatonin, indicating the downstream role of phytomelatonin in endogenous H2 control of LR formation. Consistently, extra H2 supply failed to influence the LR defective phenotypes in phytomelatonin synthetic mutants. Molecular evidence showed that the phytomelatonin-regulated auxin signaling network and cell-cycle regulation were associated with the AB/H2 control of LR branching. Also, AB and melatonin had little effect on LR branching in the presence of auxin synthetic inhibitors. Collectively, our integrated approaches show that supplying H2 via AB increases LR branching via phytomelatonin signaling. This finding might open the way for applying hydrogen storage materials to horticultural production.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Amônia/farmacologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Ácidos Indolacéticos/farmacologia , Hidrogênio , Raízes de Plantas/genética , Regulação da Expressão Gênica de Plantas
13.
Ophthalmic Res ; 67(1): 115-124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37989114

RESUMO

INTRODUCTION: The aim of this study was to explore the association between parental myopia and high myopia with children's refraction and ocular biometry in large-scale Chinese preschool children from the Beijing Hyperopia Reserve Study. SUBJECTS/METHODS: This cross-sectional kindergarten-based study enrolled children aged 3-6 years. Cycloplegic refraction, axial length (AL), and corneal radius (CR) were measured for all children. Parents were asked to complete a questionnaire about refractive status (no myopia, mild myopia <-3 D, moderate myopia ≥-3 D and ≤-6, and high myopia >-6 D). RESULTS: The study enrolled 2,053 children (1,069 boys and 984 girls), with a mean age of 4.26 ± 0.96 years and mean spherical equivalent refraction (SER) of 1.11 ± 0.97 diopter. Of the children, 90.7% had at least one myopic parent, and 511 children (24.9%) had at least one highly myopic parent. SER decreased significantly with increasing severity of parental myopia (p < 0.001). Preschool children's myopia was independently associated with parental myopia (OR, 10.4 and 11.5 for one and two highly myopic parent[s]). Age (OR = 1.1), gender (OR = 1.7; girls as references), near work time (OR = 1.2), and both maternal (OR, 1.4 and 2.0 for moderate and high myopia) and paternal myopia (OR, 1.6 and 1.9 for moderate and high myopia) were independent risk factors for lacking hyperopia reserve. CONCLUSION: Severe parental myopia was associated with a lower SER, longer AL, and higher AL/CR ratio in preschool children. Parental myopia and near work may predispose children to faster elimination of hyperopia reserves before exposure to higher educational stress.


Assuntos
Hiperopia , Miopia , Masculino , Feminino , Humanos , Pré-Escolar , Hiperopia/diagnóstico , Estudos Transversais , Miopia/diagnóstico , Refração Ocular , Pais , Córnea , Biometria
14.
Nat Commun ; 14(1): 6963, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907455

RESUMO

Infected bone defects are a major challenge in orthopedic treatment. Native bone tissue possesses an endogenous electroactive interface that induces stem cell differentiation and inhibits bacterial adhesion and activity. However, traditional bone substitutes have difficulty in reconstructing the electrical environment of bone. In this study, we develop a self-promoted electroactive mineralized scaffold (sp-EMS) that generates weak currents via spontaneous electrochemical reactions to activate voltage-gated Ca2+ channels, enhance adenosine triphosphate-induced actin remodeling, and ultimately achieve osteogenic differentiation of mesenchymal stem cells by activating the BMP2/Smad5 pathway. Furthermore, we show that the electroactive interface provided by the sp-EMS inhibits bacterial adhesion and activity via electrochemical products and concomitantly generated reactive oxygen species. We find that the osteogenic and antibacterial dual functions of the sp-EMS depend on its self-promoting electrical stimulation. We demonstrate that in vivo, the sp-EMS achieves complete or nearly complete in situ infected bone healing, from a rat calvarial defect model with single bacterial infection, to a rabbit open alveolar bone defect model and a beagle dog vertical bone defect model with the complex oral bacterial microenvironment. This translational study demonstrates that the electroactive bone graft presents a promising therapeutic platform for complex defect repair.


Assuntos
Osteogênese , Alicerces Teciduais , Ratos , Animais , Coelhos , Cães , Biomimética , Regeneração Óssea , Diferenciação Celular , Bactérias
15.
ACS Cent Sci ; 9(10): 1927-1943, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37901168

RESUMO

Maintaining the stemness of bone marrow mesenchymal stem cells (BMMSCs) is crucial for bone homeostasis and regeneration. However, in vitro expansion and bone diseases impair BMMSC stemness, limiting its functionality in bone tissue engineering. Using a deep learning-based efficacy prediction system and bone tissue sequencing, we identify a natural small-molecule compound, dihydroartemisinin (DHA), that maintains BMMSC stemness and enhances bone regeneration. During long-term in vitro expansion, DHA preserves BMMSC stemness characteristics, including its self-renewal ability and unbiased differentiation. In an osteoporosis mouse model, oral administration of DHA restores the femur trabecular structure, bone density, and BMMSC stemness in situ. Mechanistically, DHA maintains BMMSC stemness by promoting histone 3 lysine 9 acetylation via GCN5 activation both in vivo and in vitro. Furthermore, the bone-targeted delivery of DHA by mesoporous silica nanoparticles improves its therapeutic efficacy in osteoporosis. Collectively, DHA could be a promising therapeutic agent for treating osteoporosis by maintaining BMMSC stemness.

16.
Bone Res ; 11(1): 54, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872152

RESUMO

Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate, prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy. Thus, the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.


Assuntos
Envelhecimento , Tendões , Humanos , Adulto , Ratos , Animais , Diferenciação Celular , Células-Tronco , Regeneração
17.
Gels ; 9(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37754375

RESUMO

Hydrogels are widely used in wound dressings due to their moisturizing properties and biocompatibility. However, traditional hydrogel dressings cannot monitor wounds and provide accurate treatment. Recent advancements focus on hydrogel dressings with integrated monitoring and treatment functions, using sensors or intelligent materials to detect changes in the wound microenvironment. These dressings enable responsive treatment to promote wound healing. They can carry out responsive dynamic treatment in time to effectively promote wound healing. However, there is still a lack of comprehensive reviews of hydrogel wound dressings that incorporate both wound micro-environment monitoring and treatment functions. Therefore, this review categorizes hydrogel dressings according to wound types and examines their current status, progress, challenges, and future trends. It discusses various wound types, including infected wounds, burns, and diabetic and pressure ulcers, and explores the wound healing process. The review presents hydrogel dressings that monitor wound conditions and provide tailored treatment, such as pH-sensitive, temperature-sensitive, glucose-sensitive, pressure-sensitive, and nano-composite hydrogel dressings. Challenges include developing dressings that meet the standards of excellent biocompatibility, improving monitoring accuracy and sensitivity, and overcoming obstacles to production and commercialization. Furthermore, it provides the current status, progress, challenges, and future trends in this field, aiming to give a clear view of its past, present, and future.

18.
Carbon Balance Manag ; 18(1): 17, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37668811

RESUMO

BACKGROUND: Continuous increasing carbon dioxide (CO2) has aggravated global warming and promoted urban tree planting projects for many countries. So it's imperative to select high carbon sequestering landscape tree species while considering their aesthetic values of urban green space. RESULTS: 32 tree species were selected as test objects which were commonly used in landscaping in Zhengzhou, a typical northern city of China. To assess the comprehensive carbon sequestration potential of landscape tree species in different plant configuration types, we simultaneously considered their daily net carbon sequestration per unit leaf area (wCO2), daily net carbon sequestration per unit land area (WCO2) and daily net carbon sequestration of the whole plant (QCO2) through cluster analysis. Besides that, we found out the key factors affecting carbon sequestration potential of landscape tree species by redundancy analysis. CONCLUSION: Populus, P Stenoptera, P. acerifolia among large arbors (LA), V odoratissimum, P. Serratifolia, S. oblata among small arbors (SA), and B sinica var. Parvifolia, B. Megistophylla, L quihoui among shrubs (S) were recommended for local urban green space management. Photosynthetic rate (Pn), crown area (CA) and leaf area index (LAI) were the key factors which affected the comprehensive carbon sequestration potential both for LA, SA and S.

19.
J Immunol Methods ; 521: 113550, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37661050

RESUMO

Black carp (Mylopharyngodon piceus) is an important fishery resource and the main breeding target in China. Due to the lack of an assay of immunoglobulin M (IgM) antibodies in black carp, there is no effective method to evaluate adaptive immune response, which limits immunological studies and vaccine development. The present study used mAbs (monoclonal antibodies) against serum IgM of grass carp as capture antibodies. The results of Western blot analysis indicated that these antibodies had strong affinity and specificity to IgM heavy chain in black carp serum and were used to detect the antibody titer, optimize the conditions, perform a sensitivity test, and develop an indirect ELISA (enzyme-linked immunosorbent assay) to detect specific IgM antibodies in the serum. This detection method has good specificity and is effective only for grass carp (Ctenopharyngodon idella) and black carp and not for crucian carp (Carassius aumtus), silver carp (Hypophthalmichthys molitrix), bighead carp (Hypophthalmichthys nobilis), mandarin fish (Siniperca chuatsi), black bream (Megalobrama skolkovii), or yellow catfish (Pseudobagrus fulvidraco). The lowest antigen detection level was 0.05 µg/ml. The error of experimental repetition in the same sample was 1.61-4.61%. The levels of specific IgM in black carp serum were steadily increased after immunization, peaked on day 28, and then slowly decreased. Indirect ELISA can be applied to detect the changes in specific antibodies in black carp serum. Moreover, indirect ELISA provides a convenient and reliable serological detection method for immunological research and evaluation of immune effects of a vaccine in black carp.


Assuntos
Carpas , Animais , Ensaio de Imunoadsorção Enzimática , Anticorpos Monoclonais , Imunoglobulina M , Imunidade Adaptativa
20.
Front Pharmacol ; 14: 1150829, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397485

RESUMO

Objective: Despite the use of renin-angiotensin system blockade and immunosuppressive drugs, including corticosteroids, the current treatment regimens for Immunoglobulins A nephropathy (IgAN) are severely limited. The proliferation of mesangial cell and deposition of deglycosylated human IgA1 immune complex are the most common pathologic features of IgAN. We examined the tetrandrine potential of suppressing the proliferation of mesangial cells and explored its underlying mechanisms with a focus on IgA receptor/MAPK/NF-κB signaling pathway. Methods: Standard human IgA (native IgA) were enzymatically desialylated (deS IgA) or further degalactosylated (deS/deGal IgA) using neuraminidase and ß-galactosidase. Rat glomerular mesangial cells (HBZY-1) and human renal mesangial cells (HRMC) stimulated by IgA were used to observe the suppressive effect of tetrandrine. The MTT assay was used to detect the cell viability. The protein expression of IgA receptor/MAPK/NF-κB signaling pathway was examined by Western blot. Cell cycle analysis was measured by flow cytometer. Results: Native IgA and deS IgA showed limited stimulation effect on both HBZY-1 cells and HRMCs, whereas deS/deGal IgA significantly stimulated the proliferation of both HBZY-1 cells and HRMCs (p < 0.05). Compared with non-stimulation of deS/deGal IgA, 1-3 µM of tetrandrine had stronger inhibitory effect on the proliferation of HBZY-1 cells and HRMCs with the stimulation of deS/deGal IgA (p < 0.05), suggesting that tetrandrine possibly inhibited the proliferation of mesangial cells induced by deglycosylated human IgA1 specifically. Molecular mechanism study revealed that tetrandrine decreased the expression of IgA1 receptor, CD71 and ß4GALT1, and inhibited the activation of MAPK/NF-κB significantly (p < 0.05). Moreover, these inhibitory effect of tetrandrine caused cell cycle arrest and stopped the cell growth in the S phase companied with the upregulating of cyclin A2 and downregulating of cyclin D1. Conclusion: Taken together, tetrandrine inhibited the proliferation of mesangial cells induced by enzymatically deglycosylated human IgA1 via IgA receptor/MAPK/NF-κB signaling pathway. Based on these potential molecular mechanisms, tetrandrine would be an appealing therapeutic option for IgAN.

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