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1.
Virol J ; 21(1): 172, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095779

RESUMEN

Human papillomavirus (HPV) 11/16 E6/E7 proteins have been recognized to be pivotal in viral pathogenesis. This study sought to uncover the potential mechanisms of how HPV11/16 E6/E7-transfected keratinocytes inhibit cytokine secretion in peripheral blood mononuclear cells (PBMC). Upon co-culturing HPV11/16 E6/E7-transfected keratinocytes with PBMC in a non-contact manner, we observed a marked decrease in various cytokines secreted by PBMC. To determine if this suppression was mediated by specific common secreted factors, we conducted transcriptomic sequencing on these transfected cells. This analysis identified 53 common differentially secreted genes in all four HPV-transfected cells. Bioinformatics analysis demonstrated these genes were predominantly involved in immune regulation. Results from quantitative PCR (qPCR) and an extensive literature review suggested the downregulation of 12 genes (ACE2, BMP3, BPIFB1, CLU, CST6, CTF1, HMGB2, MMP12, PDGFA, RNASE7, SULF2, TGM2), and upregulation of 7 genes (CCL17, CCL22, FBLN1, PLAU, S100A7, S100A8, S100A9), may be crucial in modulating tumor immunity and combating pathogenic infections, with genes S100A8 and S100A9, and IL-17 signaling pathway being particularly noteworthy. Thus, HPV11/16 E6/E7 proteins may inhibit cytokine secretion of immune cells by altering the expression of host-secreted genes. Further exploration of these genes may yield new insights into the complex dynamics of HPV infection.


Asunto(s)
Citocinas , Leucocitos Mononucleares , Proteínas Oncogénicas Virales , Humanos , Citocinas/metabolismo , Citocinas/genética , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Leucocitos Mononucleares/metabolismo , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Proteínas Oncogénicas Virales/inmunología , Queratinocitos/virología , Queratinocitos/inmunología , Queratinocitos/metabolismo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 11/genética , Papillomavirus Humano 11/inmunología , Perfilación de la Expresión Génica , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/genética , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Proteínas E7 de Papillomavirus/inmunología , Técnicas de Cocultivo , Interacciones Huésped-Patógeno/inmunología , Interacciones Huésped-Patógeno/genética
2.
bioRxiv ; 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39091821

RESUMEN

The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag- RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for the layer-defining transcription factors. In corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions. Together, it suggests a role for layer specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, are transiently activated not only at the core of the LPC lesion, but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, resulting in a valuable data resource to investigate brain development, function and disease.

3.
Toxicol Rep ; 13: 101682, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39006370

RESUMEN

A traditional Chinese herbal medicine formula named Huang-Lian-Jie-Du Decoction (HLJDD) has been used to cure various inflammatory diseases with a long history. However, one component of HLJDD Gardeniae fructus has remarkable liver and kidney toxicities. Therefore, it was altered with Dictamni cortex to form a modified HLJDD (MHLJDD). In this study, we aimed to evaluate the sub-chronic toxicity of the active fraction of MHLJDD (MHLJDD-F) in rats. Adult rats of both sexes were intragastrically administered with vehicle or MHLJDD-F (at the dose of 170, 340, and 680 mg/kg/day) once daily for 90 days. Half of the rats from each group were kept for an additional 30-day period to observe the drug withdrawal effect. The signs of toxicity and mortality of the rats were observed, and the body weight and food consumption were recorded. Blood was collected for hematological and biochemical analyses and major organs were weighed and harvested for histopathological examinations. The results revealed that no systemic toxicity of MHLJDD-F was found during the experiments. Organ coefficients and pathological alterations of major organs were comparable to the control rats. The no-observed adverse effect level (NOAEL) of MHLJDD-F was found up to 680 mg/kg/day. All these results demonstrated that long-term oral administration of MHLJDD-F did not cause significant toxicity, which is worthy to be widely applied as a new herbal medicine in pre-clinical and clinical studies.

4.
J Ethnopharmacol ; 334: 118533, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38971347

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum Indicum L., is a popular traditional Chinese medicine (TCM) for treatment of inflammatory diseases in China. FCI is also a functional food, and is widely used as herbal tea for clearing heat and detoxicating. AIM OF THE STUDY: To explore quality control markers of FCI based on the optimal harvest period. MATERIALS AND METHODS: First, UPLC-Q-TOF/MS based untargeted metabolomics was applied to explore the chemical profiles of FCIs collected at bud stages (BS), initial stages (IS), full bloom stages (FS) and eventual stages (ES) from eight cultivated regions in China. Subsequently, lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model and carrageenan-induced rat paw edema model were used to confirm the anti-inflammatory effect of FCIs collected at IS/FS. Then, UPLC-PDA targeted metabolomics was used to quantitatively analyze 9 constituents with anti-inflammatory activity (7 flavonoids and 2 phenolic acids) changed significantly (VIP > 4) during flowering stages. Finally, ROC curves combined with PCA analysis based on the variation of 9 active constituents in FCIs from different flowering stages were applied to screen the quality markers of FCI. RESULTS: FCIs at IS/FS had almost same chemical characteristics, but quite different from those at BS and ES. A total of 32 constituents in FCIs including flavonoids and phenolic acids were changed during flowering development. Most of the varied constituents had the highest or higher contents at IS/FS compared with those at ES, indicating that the optimal harvest period of FCI should be at IS/FS. FCI extract could effectively suppress nitric oxide (NO) production in LPS-induced RAW264.7 cells and regulate the abnormal levels of cytokines and PGE2 in carrageenan-induced paw edema model rat. The results of quantitatively analysis revealed that the variation trends of phenolic acids and flavonoids in FCIs were different during flowering development, but most of them had higher contents at IS/FS than those at ES in all FCIs collected from eight cultivated regions, except one sample from Anhui. Finally, linarin, luteolin, apigenin and 3,5-dicaffeoylquinic acid were selected as the Q-markers based on the contribution of their AUC values in ROC and clustering of PCA analysis. CONCLUSIONS: Our study demonstrates the optimal harvest period of FCI and specifies the multi-constituents Q-markers of FCI based on the influence of growth progression on the active constituents using untargeted/targeted metabolomics. The findings not only greatly increase the utilization rate of FCI resources and improve quality control of FCI products, but also offer new strategy to identify the Q-markers of FCI.

5.
J Asian Nat Prod Res ; : 1-14, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958645

RESUMEN

Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products.

6.
BMC Biol ; 22(1): 159, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075446

RESUMEN

BACKGROUND: Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. RESULTS: Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. CONCLUSIONS: Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.


Asunto(s)
Redes Reguladoras de Genes , Preeclampsia , ARN Largo no Codificante , Preeclampsia/genética , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Femenino , Embarazo , Placenta/metabolismo
7.
Fitoterapia ; 177: 106087, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897250

RESUMEN

Herbal medicine pair, composed of two single herbs, is a relatively fixed minimum prescription unit in the traditional Chinese medicine's formula and has special significance in clinic. The combination of Xiangfu (the rhizoma of Cyperus rotundus L, XF) and Chuanxiong (the rhizoma of Ligusticum chuanxiong Hort, CX) has been recoded as an herbal medicine pair XF-CX in the Yuan Dynasty (1347 CE) of China and widely used in traditional Chinese medicine formula, including Chaihu Shugan San, which has been clinically used for treatment of depression. However, the optimal ratio of the XF-CX herbal medicine pair and its antidepressant constituents are still unclear. Herein, the antidepressive-like effects of XF-CX herbal medicine pairs with different ratios of XF and CX (2:1, 1:1, 1:2) were evaluated using behavioral despair animal models in mice, and then its potential antidepressant constituents were recognized by spectrum-effect relationship analyses. Finally, the potential antidepressant constituents of the XF-CX herbal medicine pair were validated by molecular docking with glucocorticoid receptor and corticosterone (CORT)-induced PC12 cell injury model. The results indicated that different ratios of XF-CX pairs had antidepressive-like effects, and the XF-CX (2:1) exhibited a more significant effect. Thirty-two potential antidepressant constituents in the XF-CX herbal medicine pair were screened out from the spectrum-effect relationship combined molecular docking analyses. Among them, senkyunolide A, cyperotundone, Z-ligustilide, and levistilide A were validated to have protective effects against CORT-induced injury in PC12 cells. Our findings not only obtained the optimal ratio of XF-CX in the herbal medicine pair for the treatment of depression but also its potential antidepressant constituents, which will benefit in elucidating the mechanism of action and promoting the application of the herbal medicine pair in the clinic.

8.
Adv Sci (Weinh) ; 11(21): e2309002, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38569496

RESUMEN

Preeclampsia (PE) is considered as a disease of placental origin. However, the specific mechanism of placental abnormalities remains elusive. This study identified thrombospondin-1 (THBS1) is downregulated in preeclamptic placentae and negatively correlated with blood pressure. Functional studies show that THBS1 knockdown inhibits proliferation, migration, and invasion and increases the cycle arrest and apoptosis rate of HTR8/SVneo cells. Importantly, THBS1 silencing induces necroptosis in HTR8/SVneo cells, accompanied by the release of damage-associated molecular patterns (DAMPs). Necroptosis inhibitors necrostatin-1 and GSK'872 restore the trophoblast survival while pan-caspase inhibitor Z-VAD-FMK has no effect. Mechanistically, the results show that THBS1 interacts with transforming growth factor B-activated kinase 1 (TAK1), which is a central modulator of necroptosis quiescence and affects its stability. Moreover, THBS1 silencing up-regulates the expression of neuronal precursor cell-expressed developmentally down-regulated 4 (NEDD4), which acts as an E3 ligase of TAK1 and catalyzes K48-linked ubiquitination of TAK1 in HTR8/SVneo cells. Besides, THBS1 attenuates PE phenotypes and improves the placental necroptosis in vivo. Taken together, the down-regulation of THBS1 destabilizes TAK1 by activating NEDD4-mediated, K48-linked TAK1 ubiquitination and promotes necroptosis and DAMPs release in trophoblast cells, thus participating in the pathogenesis of PE.


Asunto(s)
Quinasas Quinasa Quinasa PAM , Necroptosis , Ubiquitina-Proteína Ligasas Nedd4 , Preeclampsia , Trombospondina 1 , Trofoblastos , Ubiquitinación , Humanos , Preeclampsia/metabolismo , Preeclampsia/genética , Femenino , Embarazo , Trofoblastos/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Quinasas Quinasa Quinasa PAM/genética , Necroptosis/genética , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Ubiquitina-Proteína Ligasas Nedd4/genética , Trombospondina 1/metabolismo , Trombospondina 1/genética , Adulto , Placenta/metabolismo
9.
J Ethnopharmacol ; 329: 118127, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38583728

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Shugan Xiaozhi (SGXZ) decoction is a traditional Chinese medicine used for treating nonalcoholic steatohepatitis (NASH). It has been used clinically for over 20 years and proved to be effective; however, the molecular mechanism underlying the effects of SGXZ decoction remains unclear. AIM OF THE STUDY: We analyzed the chemical components, core targets, and molecular mechanisms of SGXZ decoction to improve NASH through network pharmacology and in vivo experiments. MATERIALS AND METHODS: The chemical components, core targets, and related signaling pathways of SGXZ decoction intervention in NASH were predicted using network pharmacology. Molecular docking was performed to verify chemical components and their core targets. The results were validated in the NASH model treated with SGXZ decoction. Mouse liver function was assessed by measuring ALT and AST levels. TC and TG levels were determined to evaluate lipid metabolism, and lipid deposition was assessed via oil red O staining. Mouse liver damage was determined via microscopy following hematoxylin and eosin staining. Liver fibrosis was assessed via Masson staining. Western blot (WB) and immunohistochemical (IHC) analyses were performed to detect inflammation and the expression of apoptosis-related proteins, including IL-1ß, IL-6, IL-18, TNF-α, MCP1, p53, FAS, Caspase-8, Caspase-3, Caspase-9, Bax, Bid, Cytochrome c, Bcl-2, and Bcl-XL. In addition, WB and IHC were used to assess protein expression associated with the TLR4/MyD88/NF-κB pathway. RESULTS: Quercetin, luteolin, kaempferol, naringenin, and nobiletin in SGXZ decoction were effective chemical components in improving NASH, and TNF-α, IL-6, and IL-1ß were the major core targets. Molecular docking indicated that these chemical components and major core targets might interact. KEGG pathway analysis showed that the pathways affected by SGXZ decoction, primarily including apoptosis and TLR4/NF-κB signaling pathways, interfere with NASH. In vivo experiments indicated that SGXZ decoction considerably ameliorated liver damage, fibrosis, and lipid metabolism disorder in MCD-induced NASH mouse models. In addition, WB and IHC verified the underlying molecular mechanisms of SGXZ decoction as predicted via network pharmacology. SGXZ decoction inhibited the activation of apoptosis-related pathways in MCD-induced NASH mice. Moreover, SGXZ decoction suppressed the activation of TLR4/MyD88/NF-κB pathway in MCD-induced NASH mice. CONCLUSION: SGXZ decoction can treat NASH through multiple targets and pathways. These findings provide new insights into the effective treatment of NASH using SGXZ decoction.


Asunto(s)
Apoptosis , Medicamentos Herbarios Chinos , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Enfermedad del Hígado Graso no Alcohólico , Transducción de Señal , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones , Transducción de Señal/efectos de los fármacos , Deficiencia de Colina/complicaciones , Inflamación/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Modelos Animales de Enfermedad , Farmacología en Red , Antiinflamatorios/farmacología , Metabolismo de los Lípidos/efectos de los fármacos
10.
J Ethnopharmacol ; 328: 118113, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38548119

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Tianma-Gouteng Pair (TGP), commonly prescribed as a pair-herbs, can be found in many Chinese medicine formulae to treat brain diseases. However, the neuroprotective effects and molecular mechanisms of TGP remained unexplored. AIM OF THE STUDY: This study investigated the difference between the TgCRND8 and 5 × FAD transgenic mice, the anti-AD effects of TGP, and underlying molecular mechanisms of TGP against AD through the two mouse models. METHODS: Briefly, three-month-old TgCRND8 and 5 × FAD mice were orally administered with TGP for 4 and 6 months, respectively. Behavioral tests were carried out to determine the neuropsychological functions. Moreover, immunofluorescence and western blotting assays were undertaken to reveal the molecular mechanisms of TGP. RESULTS: Although TgCRND8 and 5 × FAD mice had different beta-amyloid (Aß) burdens, neuroinflammation status, and cognition impairments, TGP exerted neuroprotective effects against AD in the two models. In detail, behavioral tests revealed that TGP treatment markedly ameliorated the anxiety-like behavior, attenuated the recognition memory deficits, and increased the spatial learning ability as well as the reference memory of TgCRND8 and 5 × FAD mice. Moreover, TGP treatment could regulate the beta-amyloid precursor protein (APP) processing by inhibiting the Aß production enzymes such as ß- and γ-secretases and activating Aß degrading enzyme to reduce Aß accumulation. In addition, TGP reduced the Aß42 level, the ratio of Aß42/Αß40, Aß accumulation, and tau hyperphosphorylation in both the 5 × FAD and TgCRND8 mouse models. Furthermore, TGP ameliorated neuroinflammation by decreasing the densities of activated microglia and astrocytes, and inhibiting the production of inflammatory cytokines. TGP upregulated the SIRT1 and AMPK, and downregulated sterol response element binding protein 2 (SREBP2) in the brain of TgCRND8 mice and deactivation of the EPhA4 and c-Abl in the brain tissues of 5 × FAD mice. CONCLUSION: Our experiments for the first time revealed the neuroprotective effects and molecular mechanism of TGP on 5 × FAD and TgCRND8 transgenic mouse models of different AD stages. TGP decreased the level of Aß aggregates, improved the tauopathy, and reduced the neuroinflammation by regulation of the SIRT1/AMPK/SREBP2 axis and deactivation of EPhA4/c-Abl signaling pathway in the brains of TgCRND8 and 5 × FAD mice, respectively. All these findings unequivocally confirmed that the TGP would be promising in developing into an anti-AD therapeutic pharmaceutical.


Asunto(s)
Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Ratones Transgénicos , Sirtuina 1 , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Enfermedades Neuroinflamatorias , Proteínas Quinasas Activadas por AMP , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Cognición , Modelos Animales de Enfermedad
11.
World J Stem Cells ; 16(2): 176-190, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38455106

RESUMEN

BACKGROUND: Cartilage defects are some of the most common causes of arthritis. Cartilage lesions caused by inflammation, trauma or degenerative disease normally result in osteochondral defects. Previous studies have shown that decellularized extracellular matrix (ECM) derived from autologous, allogenic, or xenogeneic mesenchymal stromal cells (MSCs) can effectively restore osteochondral integrity. AIM: To determine whether the decellularized ECM of antler reserve mesenchymal cells (RMCs), a xenogeneic material from antler stem cells, is superior to the currently available treatments for osteochondral defects. METHODS: We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70% confluence; 50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition. Decellularized sheets of adipocyte-derived MSCs (aMSCs) and antlerogenic periosteal cells (another type of antler stem cells) were used as the controls. Three weeks after ascorbic acid stimulation, the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints. RESULTS: The defects were successfully repaired by applying the ECM-sheets. The highest quality of repair was achieved in the RMC-ECM group both in vitro (including cell attachment and proliferation), and in vivo (including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues). Notably, the antler-stem-cell-derived ECM (xenogeneic) performed better than the aMSC-ECM (allogenic), while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells. CONCLUSION: Decellularized xenogeneic ECM derived from the antler stem cell, particularly the active form (RMC-ECM), can achieve high quality repair/reconstruction of osteochondral defects, suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

12.
Ear Hear ; 45(4): 827-836, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38351499

RESUMEN

OBJECTIVES: Recent studies have suggested that older adults with hearing loss (HL) are at a greater risk of postural instability than those with normal hearing. However, little is known regarding this association in middle-aged individuals. The relationships between HL laterality, asymmetric hearing, and posture control are similarly unclear. The purpose of this study was to investigate the effects of hearing status on postural control and to explore the dose-response relationship between the hearing threshold and postural instability risk in middle-aged adults. DESIGN: This cross-sectional study included 1308 participants aged 40 to 69 years with complete audiometric and standing balance function data from the 2001-2004 National Health and Nutrition Examination Survey. Speech-frequency HL was defined as a pure-tone average at 0.5, 1, 2, and 4 kHz of >25 dB in the better-hearing ear; high-frequency HL was defined as a pure-tone average at 3, 4, and 6 kHz of >25 dB. Asymmetric hearing was defined as a difference in the pure-tone average >15 dB between ears. Postural instability was defined as participants ending the modified Romberg test in condition 4. RESULTS: After adjustment for sociodemographic variables, lifestyle, and comorbidities, speech-frequency HL, except for unilateral HL, was associated with increased postural instability (mild HL: odds ratio [OR], 2.33; 95% confidence interval [CI], 1.25-4.35; moderate-to-severe HL: OR, 3.59; 95% CI, 1.61-8.03). Compared with individuals with normal bilateral hearing, participants with bilateral HL also showed a higher risk of postural instability (OR, 2.88; 95% CI, 1.61-5.14). The OR for postural instability among participants with asymmetric hearing compared with those with symmetric hearing was 2.75 (95% CI, 1.37-5.52). Furthermore, each 10 dB increase in the speech-frequency hearing threshold was associated with a 44% higher risk of postural instability. CONCLUSIONS: Hearing loss is associated with poorer postural control. Individuals with asymmetric hearing have a higher postural instability risk compared with those with symmetric hearing. Further studies are needed to confirm these findings and the causality. Moreover, future studies are warranted to assess whether hearing aids are beneficial for the restoration of impaired balance functions.


Asunto(s)
Audiometría de Tonos Puros , Equilibrio Postural , Humanos , Persona de Mediana Edad , Masculino , Equilibrio Postural/fisiología , Femenino , Anciano , Estudios Transversales , Adulto , Pérdida Auditiva Unilateral/fisiopatología , Umbral Auditivo , Pérdida Auditiva de Alta Frecuencia/fisiopatología , Pérdida Auditiva/fisiopatología
13.
BMC Cancer ; 24(1): 217, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38360572

RESUMEN

OBJECTIVE: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer. METHODS: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared. RESULTS: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001). CONCLUSION: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.


Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Niño , Humanos , Neoplasias del Cuello Uterino/patología , Quimioradioterapia/efectos adversos , Ganglios Linfáticos/patología , Supervivencia sin Enfermedad , Escisión del Ganglio Linfático , Estudios Retrospectivos , Estadificación de Neoplasias , Histerectomía
14.
J Asian Nat Prod Res ; 26(1): 26-37, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38196236

RESUMEN

Eight new caffeoyl derivatives, elephantomentosides A-H (1 - 8), together with ten known ones (9 - 18), were isolated from the whole plant of Elephantopos tomentosus L. Their structures were elucidated using detailed spectroscopic analysis. Structurally, compounds 1 - 8 are composed of ß-D-glucopyranose, and almost all of the substituent positions are at the C-1' and C-4' of glucopyranose. The anti-inflammatory and antioxidant activities of all isolated compounds were evaluated in vitro. Compounds 9-10, 13-15, and 17-18 exhibited significant DPPH scavenging capacity with IC50 values in the range of 10.01-25.07 µM, in comparison with Vc (IC50, 17.98 µM).


Asunto(s)
Antioxidantes , Asteraceae , Estructura Molecular , Antioxidantes/farmacología , Antioxidantes/química , Asteraceae/química , Antiinflamatorios/farmacología , Antiinflamatorios/química
15.
Virol J ; 21(1): 10, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-38183109

RESUMEN

Human papillomavirus (HPV) infection poses a significant threat to public health worldwide. Targeting the function of HPV E6 and E7 proteins and activating the host immune response against these proteins represent promising therapeutic strategies for combating HPV-related diseases. Consequently, the efficient production of soluble, high-purity E6 and E7 proteins is crucial for function and host immune response studies. In this context, we selected the pMCSG19 protein expression vector for Escherichia coli to produce soluble MBP-His6 tagged HPV11/16 E6/E7 proteins, achieving relatively high purity and yield. Notably, these proteins exhibited low toxicity to peripheral blood mononuclear cells (PBMCs) and did not compromise their viability. Additionally, the recombinant proteins were capable of inducing the secretion of multiple cytokines by immune cells in peripheral blood, indicating their potential to elicit immune responses. In conclusion, our study offers a novel approach for the production of HPV11/16 E6/E7 fusion proteins with relatively high purity and yield. The fusing HPV11/16 E6/E7 proteins to MBP-His6 tag may serve as a valuable method for large-scale protein production in future research endeavors.


Asunto(s)
Leucocitos Mononucleares , Infecciones por Papillomavirus , Humanos , Citocinas , Escherichia coli/genética , Proteínas Recombinantes/genética
16.
J Transl Med ; 22(1): 7, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167140

RESUMEN

BACKGROUND: Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in preterm birth (PTB) pathophysiology, increasing the incidence of neurodevelopmental disorders. Gut microbiota and metabolite profile alterations have been reported to be involved in PTB pathophysiology. METHOD AND RESULTS: In this study, IUI-exposed PTB mouse model was established and verified by PTB rate and other perinatal adverse reactions; LPS-indued IUI significantly increased the rates of PTB, apoptosis and inflammation in placenta tissue samples. LPS-induced IUI caused no significant differences in species richness and evenness but significantly altered the species abundance distribution. Non-targeted metabolomics analysis indicated that the metabolite profile of the preterm mice was altered, and differential metabolites were associated with signaling pathways including pyruvate metabolism. Furthermore, a significant positive correlation between Parasutterella excrementihominis and S4572761 (Nb-p-coumaroyltryptamine) and Mreference-1264 (pyruvic acid), respectively, was observed. Lastly, pyruvic acid treatment partially improved LPS-induced IUI phenotypes and decreased PTB rates and decreased the apoptosis and inflammation in placenta tissue samples. CONCLUSION: This study revealed an association among gut microbiota dysbiosis, metabolite profile alterations, and LPS-induced IUI and PTB in mice models. Our investigation revealed the possible involvement of gut microbiota in the pathophysiology of LPS-induced IUI and PTB, which might be mediated by metabolites such as pyruvic acid. Future studies should be conducted to verify the findings through larger sample-sized animal studies and clinical investigations.


Asunto(s)
Microbioma Gastrointestinal , Nacimiento Prematuro , Recién Nacido , Embarazo , Humanos , Femenino , Animales , Ratones , Lipopolisacáridos/farmacología , Nacimiento Prematuro/etiología , Ácido Pirúvico/efectos adversos , Inflamación/metabolismo , Inseminación Artificial
17.
Environ Pollut ; 342: 123090, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38072026

RESUMEN

Perfluorooctanoic acid (PFOA) is a widely used industrial compound that has been found to induce intestinal toxicity. However, the underlying mechanisms have not been fully clarified and effective interventions are rarely developed. Inulin, a prebiotic, has been used as a supplement in human daily life as well as in gastrointestinal diseases and metabolic disorders. In this study, male mice were exposed to PFOA with or without inulin supplementation to investigate the enterotoxicity and potential intervention effects of inulin. Mice were administered PFOA at 1 mg/kg/day, PFOA with inulin at 5 g/kg/day, or Milli-Q water for 12 weeks. Histopathological analysis showed that PFOA caused colon shortening, goblet cell reduction, and inflammatory cell infiltration. The expression of the tight junction proteins ZO-1, occludin and claudin5 significantly decreased, indicating impaired barrier function. According to the RNA-sequencing analysis, PFOA exposure resulted in 917 differentially expressed genes, involving 39 significant pathways, such as TNF signaling and cell cycle pathways. In addition, the protein expression of TNF-α, IRG-47, cyclinB1, and cyclinB2 increased, while Gadd45γ, Lzip, and Jam2 decreased, suggesting the involvement of the TNF signaling pathway, cell cycle, and cell adhesion molecules in PFOA-associated intestinal injury. Inulin intervention alleviated PFOA-induced enterotoxicity by activating the PI3K/AKT/mTOR signaling pathway and increasing the protein expression of Wnt1, ß-catenin, PI3K, Akt3, and p62, while suppressing MAP LC3ß, TNF-α, and CyclinE expression. These findings suggested that PFOA-induced intestinal injury, including inflammation and tight junction disruption, was mitigated by inulin through modifying the PI3K/AKT/mTOR signaling pathways. Our study provides valuable insights into the enterotoxic effects of PFOA and highlights the potential therapeutic role of inulin.


Asunto(s)
Caprilatos , Fluorocarburos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Humanos , Masculino , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Inulina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
18.
J Ethnopharmacol ; 322: 117637, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38135226

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Constipation is one of the most prevalent gastrointestinal tract diseases that seriously affects health-related quality of human life and requires effective treatments without side effect. The rhizome of Atractylodes macrocephala Koidz. (Compositae), called Atractylodes Macrocephala Rhizome (AMR), a commonly used traditional Chinese medicine, has been used to relieve the clinical symptoms of patients with constipation. AIM OF THE STUDY: To reveal the dose-dependent laxative effect and potential mechanism of AMR on loperamide-induced slow transit constipation (STC) rats. MATERIALS AND METHODS: Loperamide-induced constipation rat model was established and the dose-dependent laxative effect of AMR was investigated. Untargeted metabolomics based on an UPLC-Q/TOF-MS technique combined with western blot analysis was used to explain the potential mechanism of AMR relieve loperamide-induced constipation in rats. RESULTS: The results showed that medium dose of AMR (AMR-M, 4.32 g raw herb/kg) and high dose of AMR (AMR-H, 8.64 g raw herb/kg) treatments significantly increased the fecal water content, Bristol score, gastrointestinal transit rate, and recovered the damaged colon tissues of constipated rats, but low dose of AMR (AMR-L, 2.16 g raw herb/kg) did not show laxative effect. Both AMR-M and AMR-H treatments also remarkably reduced the serum levels of vasoactive intestinal peptide (VIP), somatostatin (SS) and dopamine (DA), and increased the levels of motilin (MTL), gastrin (GAS) and 5-hydroxytryptamine (5-HT). Urine metabolomics revealed that constipation development was mainly ascribed to the perturbed tryptophan metabolism, and AMR-M and AMR-H markedly corrected the abnormal levels of five urine tryptophan metabolites, namely 4,6-dihydroxyquinoline, indole, 4,8-dihydroxyquinoline, 5-hydroxytryptamine, and kynurenic acid. Additionally, western blot analysis confirmed that the abnormal expression of rate-limiting enzyme involving in tryptophan metabolism, including tryptophan hydroxylase (TPH), monoamine oxidase (MAO) and indoleamine-2,3-dioxygenase (IDO) in the colon of constipated rats, were mediated by AMR-M and AMR-H. CONCLUSIONS: The findings provide insight into the mechanisms of STC and AMR could be developed as new therapeutic agent for prevention or healing of constipation.


Asunto(s)
Atractylodes , Loperamida , Ratas , Humanos , Animales , Loperamida/uso terapéutico , Laxativos/farmacología , Atractylodes/química , Triptófano , Rizoma/química , Serotonina , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico
19.
Work ; 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38160380

RESUMEN

BACKGROUND: In a previous study, more attention has been given to the psychological state of doctors than to that of nurses although the workload, working hours, and patient contact time are generally higher for nurses than doctors. The current status of nurses' perceived stress, work engagement, and perceived professional benefit during the routine management of the Corona Virus Disease 2019(COVID-19) pandemic and how their perceived stress affects the other two variables are topics that merit research attention. OBJECTIVE: In this study, the status of nurses' perceived stress, work engagement, and perceived professional benefit during the routine management of the Corona Virus Disease 2019 pandemic was investigated to explore whether their perceived stress level has any effect on the other two variables. METHODS: The convenience sampling method was adopted, and 669 nurses from the First People's Hospital of Jingzhou were selected to participate in this study. Questionnaires on perceived stress, work engagement, and perceived professional benefit were used in the survey, and the data were processed using the SPSS 20.0 program for the descriptive statistics, independent sample t-test, analysis of variance. RESULTS: The total score of the nurses' perceived stress was 18.58±4.37 points. The total scores of their work engagement (43.32±14.01) and perceived professional benefit (140.23±17.75). CONCLUSION: The nurses' total perceived stress score was at an upper-middle level, and their total work engagement and perceived professional benefit scores were relatively high. Overall, perceived stress has a negative effect on nurses' work engagement and perceived professional benefit. That is, the higher the pressure perception of nurses, the lower the degree of work engagement and perceived professional benefit.

20.
Placenta ; 144: 45-54, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37992596

RESUMEN

INTRODUCTION: Selective intrauterine growth restriction (sIUGR), which specifically occurs in monochorionic (MC) twins, usually has a poor prognosis and the underlying mechanisms are not well understood. It is an ideal model for exploring epigenetic-modified mechanisms for fetal development in MCDA twins due to eliminating the interference of different heritable backgrounds and intrauterine environments among individuals. METHODS: The levels of ten-eleven translocation 2 (TET2) and its upstream and downstream targets miR-29b-3p and transforming growth factor beta 1 (TGFB1) were determined using RT‒qPCR, western blotting, and immunohistochemistry. Using TET2 overexpression and knockdown methods, we investigated the role of TET2 in trophoblast functions. The regulatory relationships among TET2, miR-29b-3p, and TGFB1 were explored by cell migration assay, invasion assay, apoptotic ratio assays, Western blot, hMeDIP-qPCR and dual-luciferase assay. RESULTS: A consistent upregulation of TET2 and TGFB1 was observed in the smaller placental shares compared to the larger placental shares in sIUGR. Gain-of-function studies of TET2 in trophoblasts showed decreased cell invasion and increased apoptosis, whereas loss-of-function studies of TET2 rescued this effect. Mechanistic studies revealed that miR-29b-3p and TGFB1 were the upstream factor and downstream target of TET2, respectively. Furthermore, miR-29b-3p/TET2/TGFB1-smad was identified as a unique axis that regulates trophoblast invasion, migration, and apoptosis in a DNA hydroxymethylation-dependent manner. DISCUSSION: We elucidated the functional roles of TET2 and DNA hydroxymethylation in trophoblasts and identified a novel DNA regulatory mechanism, providing a basis for further exploration of DNA epigenetic regulatory patterns in sIUGR.


Asunto(s)
Dioxigenasas , MicroARNs , Femenino , Humanos , Embarazo , Dioxigenasas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Retardo del Crecimiento Fetal/genética , Retardo del Crecimiento Fetal/metabolismo , MicroARNs/metabolismo , Placenta/metabolismo , Embarazo Gemelar , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Trofoblastos/metabolismo , Gemelos Monocigóticos , Metilación de ADN
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