RESUMO
OBJECTIVE: To explore the factors related to cesarean scar pregnancy (CSP) treatment failure under different treatment strategies. METHODS: This is a cohort study that consecutively included 1637 patients with CSP. Characteristics including age, gravidity, parity, previous uterine curettages, time since the last cesarean section, gestational age, mean sac diameter, initial serum ß-human chorionic gonadotropin, distance between gestational sac and serosal layer, CSP subtype, classification of blood flow abundance, fetal heartbeat presence, and intraoperative bleeding were recorded. Four strategies were performed separately on these patients. Binary logistic regression analysis was used to analyze the risk factors for initial treatment failure (ITF) under the different treatment strategies. RESULTS: The treatment methods failed in 75 CSP patients, and succeeded in 1298 patients. The analysis found that the presence of a fetal heartbeat was significantly associated with ITF of strategy 1, 2 and 4 (P < 0.05); sac diameter was associated with ITF of strategy 1 and 2 (P < 0.05); gestational age was associated with initial treatment failure of strategy 2 (P < 0.05). CONCLUSION: There was no difference of the failure rate between ultrasound-guided evacuation and hysteroscopy-guided evacuation for CSP treatment with or without uterine artery embolization pretreatment. Sac diameter, fetal heartbeat presence, and gestational age were all associated with CSP initial treatment failure.
Assuntos
Cesárea , Cicatriz , Humanos , Gravidez , Feminino , Cesárea/efeitos adversos , Cicatriz/complicações , Cicatriz/terapia , Estudos de Coortes , Fatores de Risco , Número de GestaçõesRESUMO
BACKGROUND: The mechanisms underlying the pathogenesis of preeclampsia (PE) remains unclear. Exploring the molecular players in PE progression can provide insights into targeted therapy. METHODS: The expression levels of circSTAM in placental chorionic tissues of PE patients and normal pregnant women were compared by RT-qPCR. CircSTAM was knocked down by small interfering RNA to investigate its role in migration, invasion and epithelial-mesenchymal transformation (EMT) of trophoblast HTR-8/SVneo cells. The downstream target of circSTAM was predicted using online bioinformatics resources, and their molecular interaction was examined by luciferase reporter assay. RESULTS: CircSTAM was upregulated in PE placenta tissues in comparison to normal placental tissues. CircSTAM knockdown significantly enhanced cellular invasion, migration, as well as EMT. Mir-148a-5p was identified as a target of circSTAM to regulate cell migration and invasion. Mir-148a-5p negatively regulated PTEN expression in trophoblast HTR-8 /SVneo cells. CONCLUSION: In summary, circSTAM upregulation in PE trophoblasts promoted the invasion, migration and EMT. CircSTAM may modulate trophoblast phenotype by impinging on mir-148a-5p/PTEN axis. These data provided novel insights into the pathogenesis of PE.
Assuntos
MicroRNAs , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Interferente Pequeno , Trofoblastos/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Annexin A5 (ANXA5) haplotypes can increase the risk of recurrent pregnancy loss (RPL). This study aimed to investigate the effect of ANXA5 haplotypes on ANXA5 expression in patients with RPL. METHODS: Female subjects with RPL, parous controls (those who intentionally aborted without medical conditions or complications), and population controls (normal delivery) were studied. Real-time polymerase chain reaction was carried out to evaluate ANXA5 expression in the placenta and peripheral blood. Western blotting and immunohistochemistry were used to assess ANXA5 protein expression. The luciferase assay was performed to detect the effect of M1 and M2 haplotypes on transcription efficiency of the ANXA5 promoter. RESULTS: We found that the percentage of the M2 carrier was highest in the RPL group. ANXA5 expression in the placenta and peripheral blood in subjects with RPL was significantly inhibited. Furthermore, ANXA5 expression in subjects carrying the M2 haplotype was remarkably suppressed compared with that in carriers of other haplotypes. Finally, the M2 haplotype decreased the transcription efficiency of the ANXA5 promoter. CONCLUSION: Our findings show that ANXA5 expression is decreased in carriers of the M2 haplotype and that M1/M2 haplotypes in the ANXA5 gene are associated with an increased risk of RPL.
Assuntos
Aborto Habitual , Aborto Habitual/epidemiologia , Aborto Habitual/genética , Anexina A5/genética , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Gravidez , Regiões Promotoras Genéticas , Fatores de RiscoRESUMO
BACKGROUND: Recently, the SARS-CoV-2 variant of concern, Omicron (B.1.1.529), was identified as responsible for a novel wave of COVID-19 worldwide. Here, we compared initial clinical features of hospitalized COVID-19 patients during recent wave (Omicron Variant) with those in ancestral variant wave (2020). METHODS: This is a cohort study of electronic health record (EHR) data from a signal center in the China. The clinical data of 116 cases of Omicron hospitalized in 2022 and 87 cases hospitalized in 2020 were collected. The comparisons were performed with the Mann-Whitney U test, Fisher exact test or the chi-square test, and multivariable logistic regression analysis. RESULTS: Clinically, compared with 2020-cohort, Omicron-cohort was more inclined to cluster in younger population and had more nonsymptomatic (25.0%) and nonsevere cases, as well as suffered from comparable extrapulmonary complication. Radiologically, although the major computed tomography (CT) findings of both cohorts were ground-glass opacities (GGOs), crazy-paving pattern was relatively less seen in the Omicron-cohort. Based on multiple logistic regression analysis, Omicron-cohort was associated with a lower risk of complaining with fever, the presence of lung opacity, and increased Sequential Organ Failure Assessment (SOFA) score. CONCLUSION: This study provided the data of different patterns of clinic characteristics and reduced severity from infections that occurred in Omicron variant as compared with the outbreak of the epidemic in 2020 wave (ancestral variant).
Assuntos
COVID-19 , SARS-CoV-2 , Estudos de Coortes , Humanos , Tomografia Computadorizada por Raios X/métodosRESUMO
Recurrent miscarriage (RM) is one of the common complications of pregnancy, which is closely related to gene mutation. The profiling of non-coding RNAs showed that the expression level of long non-coding RNA LINC01347 (LINC01347) in the serum of patients with recurrent abortion was significantly increased, which could serve as a potential marker for early diagnosis. However, the biological functions of LINC01347 in the miscarriage remain to be elucidated. In this study, LINC01347 expression levels in HTR-8/SVneo cells and placenta samples were measured by RT-qPCR. The migration ability of HTR-8/SVneo cells was detected by wound-healing assay. Western blotting (WB) assay was conducted to measure E-cadherin, Vimentin, N-cadherin, PTEN, phospho-AKT(S473), phospho-AKT(T308) and AKT levels. Dual luciferase reporter assay and RNA pull-down analysis were performed to validate the molecular interactions. The results showed an upregulation of LINC01347 in the placenta samples of RM patients and HTR-8/SVneo cells. LINC01347 overexpression impaired the invasion and migration of trophoblast cells, while LINC01347 silencing promoted cell migration and invasion. LINC01347 level was also negatively correlated with the changes of epithelial-mesenchymal transition (EMT) markers in trophoblasts. We further demonstrated that miR-101-3p/PTEN/AKT axis played an important role in mediating the biological roles of LINC01347 in the invasion and migration of trophoblasts. In conclusion, our results revealed that LINC01347 suppresses the migratory ability and regulates the EMT processes in trophoblasts by regulating miR-101-3p/PTEN/AKT axis, suggesting that targeting LINC01347 may serve as a strategy to ameliorate RM.
Assuntos
Aborto Habitual , RNA Longo não Codificante , Trofoblastos , Aborto Habitual/genética , Aborto Habitual/metabolismo , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Trofoblastos/metabolismoRESUMO
Transient receptor potential vanillic acid 2 (TRPV2) are well recognized for their contributions to neuronal development, cardiac function, immunity and cancer. However, the precise roles for this thermo TRPchannels in neurological disorder remain unknown. In this study, we employed the CRISPR/Cas9 system to generate genetic mutations of TRPV2. Genetic mutation of TRPV2 resulted in autistic-like phenotypes in mice accompanied with the disordered electrical signals recorded by multi-channels in vivo. To determine possible molecular mechanisms, western blotting was further used to assess the possible involvement of several autism-related proteins. The significantly decreased expression of the R2 subunit of the GABA-B receptor in the hippocampus was observed. Together, our findings suggest that genetic mutation of TRPV2 induces autism-like behavior, results in decreased expression of the R2 subunit of the GABA-B receptor.
Assuntos
Ansiedade/genética , Receptores de GABA-B , Canais de Cátion TRPV , Animais , Canais de Cálcio/metabolismo , Hipocampo/metabolismo , Camundongos , Mutação , Receptores de GABA-B/metabolismo , Canais de Cátion TRPV/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Recurrent spontaneous abortion (RSA) is a common complication during early gestation, which is associated with aberrant DNA methylation. Zinc Finger and BTB Domain Containing 24 (ZBTB24) plays a critical role in facilitating DNA methylation and cell proliferation. However, the regulatory role of ZBTB24 on trophoblast development in RSA remains unclear. In this study, ZBTB24 expression was compared between decidua tissues of RSA patients and induced abortion controls from a published dataset, which was further validated in placental villi tissues by RT-qPCR and Western blot. The roles of ZBTB24 in trophoblast proliferation, differentiation, and migration were investigated by functional assays after ZBTB24 knockdown or overexpression in HTR-8/SVneo cells. Our results showed that ZBTB24 expression was significantly decreased in RSA patients, and ZBTB24 expression level positively regulated cell viability, differentiation, and migration in HTR-8/SVneo cells. We further demonstrated that ZBTB24 modulated the expression of E-cadherin by altering the DNA methylation at the promoter region. Overall, the downregulation of ZBTB24 is implicated in RSA by inhibiting trophoblast proliferation, differentiation, and migration. Therefore, ZBTB24 may serve as a promising therapeutic target and diagnostic marker for RSA.
Assuntos
Aborto Habitual/metabolismo , Aborto Habitual/prevenção & controle , Movimento Celular , Proliferação de Células , Proteínas Repressoras/biossíntese , Trofoblastos/metabolismo , Aborto Habitual/genética , Decídua/metabolismo , Feminino , Humanos , Gravidez , Proteínas Repressoras/genéticaRESUMO
PURPOSE: Nanomaterial-based drug-delivery systems allowing for effective targeted delivery of smallmolecule chemodrugs to tumors have revolutionized cancer therapy. Recently, as novel nanomaterials with outstanding physicochemical properties, boron nitride nanospheres (BNs) have emerged as a promising candidate for drug delivery. However, poor dispersity and lack of tumor targeting severely limit further applications. In this study, cancer cell-membrane biomimetic BNs were designed for targeted anticancer drug delivery. METHODS: Cell membrane extracted from HeLa cells (HM) was used to encapsulate BNs by physical extrusion. Doxorubicin (Dox) was loaded onto HM-BNs as a model drug. RESULTS: The cell-membrane coating endowed the BNs with excellent dispersibility and cytocompatibility. The drug-release profile showed that the Dox@HM-BNs responded to acid pH, resulting in rapid Dox release. Enhanced cellular uptake of Dox@HM-BNs by HeLa cells was revealed because of the homologous targeting of cancer-cell membranes. CCK8 and live/dead assays showed that Dox@HM-BNs had stronger cytotoxicity against HeLa cells, due to self-selective cellular uptake. Finally, antitumor investigation using the HeLa tumor model demonstrated that Dox@HM-BNs possessed much more efficient tumor inhibition than free Dox or Dox@BNs. CONCLUSION: These findings indicate that the newly developed HM-BNs are promising as an efficient tumor-selective drug-delivery vehicle for tumor therapy.
Assuntos
Materiais Biomiméticos/química , Compostos de Boro/química , Membrana Celular/patologia , Terapia de Alvo Molecular , Nanosferas/química , Neoplasias/patologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Células HEK293 , Humanos , Camundongos Endogâmicos BALB C , Nanosferas/ultraestrutura , Neoplasias/tratamento farmacológico , Espectrometria por Raios X , Distribuição Tecidual/efeitos dos fármacosRESUMO
Preeclampsia (PE) is characterized by the impaired invasive ability of trophocytes, which can be modulated by microRNAs (miRs). In the current study, the effects of rhynchophylline (Rhy) on the viability and invasive ability of trophocytes were explored by focusing on miR-141-3p/ZEB1 axis. The level of miR-141-3p was modulated in human trophocytes and the changes in cell viability, apoptosis, invasive ability, and ZEB1 level were detected. Then the trophocytes with miR-141-3p overexpression were treated with Rhy and the effects on trophocyte phenotypes were assessed. The induced miR-141-3p level suppressed cell viability, induced apoptosis, and inhibited invasion and ZEB1 level in trophocytes. The treatment of Rhy restored the viability and invasive ability of trophocytes under the overexpression of miR-141-3p, indicating the protective effects of Rhy on trophocytes. The findings in the current study highlighted the protective effects of Rhy on trophocytes during PE progression, which was associated with the inhibition of miR-141-3p.
Assuntos
Movimento Celular/efeitos dos fármacos , MicroRNAs/genética , Oxindóis/farmacologia , Regulação para Cima/efeitos dos fármacos , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , HumanosRESUMO
The abnormal function of the voltage-gated potassium channel Kv10.2 can induce epilepsy. However, the physiological function of Kv10.2 in the central nervous system remains unclear. In this study, we found that Kv10.2 knockout (KO) increased the complexity of neurons in the CA3 subarea of hippocampus. Kv10.2 KO led to enlarged somata, elongated dendritic length, and increased the number of dendritic tips in cultured rat hippocampus neurons. Kv10.2 KO also increased Synapsin I and PSD95 protein density in cultured rat hippocampal neurons. Whole cell patch-clamp recordings of brain slices in the CA3 subarea of hippocampus revealed that Kv10.2 KO increased the amplitude of spontaneous excitatory postsynaptic currents (sEPSC) and miniature excitatory postsynaptic currents (mEPSC), depolarized the resting membrane potential and increased the action potential firing, reduced the rheobase and increased the input resistance, which results in enhanced neuronal excitability. Furthermore, we made electroencephalogram (EEG) recordings of brain activity in freely moving rats before and after inducing seizures by pentylenetetrazole (PTZ) injection. Kv10.2 KO rats dramatically increased the EEG amplitude during epilepsy. Behavioral observation after seizure induction revealed that Kv10.2 KO rats demonstrated shortened onset latency, prolonged duration, and increased seizure severity when compared with wild type rats. Therefore, this study provides a new link between Kv10.2 and neuronal morphology and higher intrinsic excitability.
Assuntos
Dendritos/metabolismo , Epilepsia/genética , Canais de Potássio Éter-A-Go-Go/deficiência , Predisposição Genética para Doença , Plasticidade Neuronal/genética , Animais , Região CA3 Hipocampal/metabolismo , Região CA3 Hipocampal/patologia , Dendritos/genética , Dendritos/patologia , Proteína 4 Homóloga a Disks-Large/metabolismo , Epilepsia/patologia , Canais de Potássio Éter-A-Go-Go/genética , Potenciais Pós-Sinápticos Excitadores/fisiologia , Técnicas de Inativação de Genes , Ratos , Sinapsinas/metabolismoRESUMO
The role of potassium channels provides suggestive evidence for the etiology of autism. The voltage-gated potassium channel Kv10.2 (KCNH5) is widely expressed in the brain. However, the inherent relationship between Kv10.2 and autism is still unclear. Herein, a rat valproic acid (VPA)-induced autism spectrum disorder model was established. The expression level of Kv10.2 was obviously decreased in the hippocampus of VPA rats. Kv10.2 was mainly localized in neurons. Subsequently, a recombinant lentivirus expressing Kv10.2 was used to upregulate the expression of Kv10.2 in the hippocampus of VPA-exposed rats. The results were promising as injection of the Kv10.2 lentivirus in the hippocampus relieved anxiety and stereotypical behavior, and improved the social and exploratory abilities of rats that were prenatally exposed to VPA. In addition, spectral analysis of electroencephalogram data revealed that animals exposed to VPA exhibited increased high-frequency activity compared with the control rats, and this activity recovered to a certain extent after upregulation of Kv10.2 expression by lentivirus injection. These results suggest that changes in Kv10.2 may play an important role in the etiology of autism, thus providing a promising direction for further research on autism.
Assuntos
Transtorno Autístico/terapia , Canais de Potássio Éter-A-Go-Go/metabolismo , Canais de Potássio Éter-A-Go-Go/uso terapêutico , Hipocampo/metabolismo , Animais , Ansiedade/metabolismo , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/etiologia , Comportamento Animal/fisiologia , Terapia Biológica , Canais de Potássio Éter-A-Go-Go/genética , Feminino , Hipocampo/patologia , Lentivirus/genética , Masculino , Gravidez , Ratos , Ácido ValproicoRESUMO
Research on anticervical cancer is urgently required to enhance clinical outcomes. As a main anticancer drug for cervical carcinoma, cisplatin (CIS) has been used for a lot of years in clinical therapy. However, serious adverse effects including nephrotoxicity and neurotoxicity limit its long-term treatment. Our main goal of this study is to investigate the improvement of Ganoderma lucidum polysaccharides (GPS) on CIS-induced antitumor effect of in U14 cervical carcinoma-bearing mice. The results showed that GPS + CIS could not only inhibit the growth of the tumor but also improve the spleen and thymus indexes. Moreover, little toxicological effects were observed on hepatic function and renal function in GPS + CIS treated mice bearing U14 tumor cells. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly, the expression of Bax increased and the expression of Bcl-2 decreased dramatically in cervical cancer sections after oral administration of GPS + CIS for 14 days. This GPS/CIS combined therapy represents intriguing therapeutic strategy for U14 cervical carcinoma providing not only superior efficacy but also a higher safety level.
Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Polissacarídeos/uso terapêutico , Reishi/química , Neoplasias do Colo do Útero/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Creatinina/sangue , Feminino , Contagem de Leucócitos , Camundongos , Polissacarídeos/farmacologia , Análise de Sobrevida , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Proteína X Associada a bcl-2/metabolismoRESUMO
Long noncoding RNAs (lncRNAs) have been discovered as significant regulators in a wide range of human cancers. Among them, lncRNA MNX1-AS1 has been proved to be an oncogene in ovarian cancer and glioblastoma. However, the regulatory mechanism of MNX1-AS1 in cervical cancer remains to be understood. Therefore, this study planned to explore the role of MNX1-AS1 in cervical cancer. In the beginning, we found that the expression of MNX1-AS1 was obviously upregulated in cervical cancer tissues and cell lines. Kaplan-Meier survival analysis revealed that patients with higher MNX1-AS1 expression level suffered from shorter overall survival time than those with lower MNX1-AS1 level. Moreover, by loss-of-function and gain-of-function assay, the effect of MNX1-AS1 on cell proliferation and apoptosis was examined on cellular level. Results showed that the proliferation of Hela cells was significantly inhibited and apoptosis enhanced by the transfection of shMNX1-AS1, while overexpressing MNX1-AS1 in E6E7 cells presented the contrary results. As for mechanism investigation, it was demonstrated that overexpression of MNX1-AS1 significantly improved the expression of p-ERK1/2 and p-JNK. And the effects of MNX1-AS1 on cell proliferation and apoptosis would be diminished after inactivating the phosphorylation of either ERK or JNK. Taken together, it was identified that MNX1-AS1 promoted proliferation and inhibited apoptosis of cervical cancer cells through MAPK pathway.
Assuntos
Progressão da Doença , Proteínas de Homeodomínio/genética , Sistema de Sinalização das MAP Quinases , RNA Antissenso , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/metabolismo , Adulto , Apoptose/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Feminino , Células HeLa , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Transfecção , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
The present study aims to reveal the mechanisms of hepatocyte apoptosis induced by dietary feeding. Eighteen midlactating goats were randomly divided into three groups: the low concentrate group (LC), the high concentrate group (HC), and the sodium butyrate (SB)-supplemented group (SHC). After 10 weeks, the HC diet successfully induced subacute ruminal acidosis (SARA), which increased the lipopolysaccharide (LPS) and cytokine concentrations and the expression of genes and proteins related to inflammation and apoptosis. The addition of SB to the HC diet notably decreased the levels of those parameters. Additionally, Bcl2 mRNA and protein expression was lower in the HC group than those in the LC and SHC groups. Furthermore, the HC diet reduced the percentages of caspase 3 and 8 promoter methylation compared to those of goats fed the LC diet, whereas the SHC diet partially recovered the methylation ratio to reduce caspase 3 and 8 expression. Collectively, HC diet-induced SARA caused hepatocyte apoptosis via activating the extrinsic apoptosis pathway, whereas dietary addition of SB depressed the inflammatory response and attenuated hepatocyte apoptosis. DNA methylation contributed to regulation of the expression of key apoptotic genes in the livers of lactating goats.
Assuntos
Acidose/veterinária , Apoptose/efeitos dos fármacos , Ácido Butírico/administração & dosagem , Suplementos Nutricionais/análise , Doenças das Cabras/tratamento farmacológico , Hepatócitos/citologia , Rúmen/metabolismo , Acidose/tratamento farmacológico , Acidose/metabolismo , Acidose/fisiopatologia , Ração Animal , Animais , Doenças das Cabras/metabolismo , Doenças das Cabras/fisiopatologia , Cabras , Hepatócitos/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacosRESUMO
Animals nurtured with a high-concentrate diet for a more extended period can cause subacute ruminal acidosis (SARA). In this study, twelve mid-lactating goats were separated into two groups (nâ¯=â¯6): a high concentrate diet (HC) control and a high concentrate with buffer (HCB) treatment group. Rumen fistula was installed in all lactating goats in the 14th week of the experiment. Goats were slaughtered in the 24th week. Our results showed that a pH valueâ¯<â¯5.8 sustained at different periods of time for more than 3â¯h/day in the group HC, which confirms that SARA was prompted efficiently. Additionally, the group HCB exhibited lower concentration of LPS in peripheral blood than the group HC. Radioimmunoassay revealed a substantial reduction in the concentration level of proinflammatory cytokines in the lacteal blood of the group HCB compared to group HC. The transcriptional profiles in mammary gland following different treatments showed a significant decrease in the expression of NOD1, IKß, and NF-κB in HCB group, followed by a decreased transcriptional level of (TNF-α, IL-1ß and IL-6). Our research explores that HC diet nurtured to lactating goats for a more extended period can induce SARA by increasing the LPS and proinflammatory cytokine concentrations in plasma, that ultimately triggers the NOD1/NF-κB inflammatory pathway and induce mammary cell inflammation. Additionally, oral supplementation of sodium butyrate can decrease the concentrations of LPS and proinflammatory cytokines and inhibits NOD1/NF-κB inflammatory pathway.
Assuntos
Acidose/veterinária , Dieta/métodos , Doenças das Cabras/patologia , Glândulas Mamárias Animais/patologia , NF-kappa B/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acidose/patologia , Animais , Ácido Butírico/metabolismo , Dieta/efeitos adversos , Perfilação da Expressão Gênica , CabrasRESUMO
Eighteen lactating goats (38.86 ± 2.06 kg) were randomly allocated to three groups. One group was fed a low-concentrate (LC) diet (forage:concentrate = 6:4), while the other two groups were fed a high-concentrate (HC) diet (forage:concentrate = 4:6) or an HC diet supplemented with sodium butyrate (BHC) for 20 weeks. Samples of ruminal fluid, milk, hepatic blood plasma, and mammary gland tissue were prepared for the experimental analysis. The lipopolysaccharide (LPS) concentration, caspase-3 and -8 enzymatic activity, caspase-3 and -8 mRNA expression, and NF-κB (p65), phosphorylated-p65, bax, cytochrome c, and caspase-3 protein expression were higher in the HC group than those in the LC group; however, the levels of these parameters were lower in the BHC group than those in the HC group. Moreover, bcl-2 mRNA and protein expression was higher in the BHC group than that in the HC or LC groups, and no significant difference was observed between the HC and LC groups. Thus, feeding lactating goats an HC diet induces apoptosis in mammary cells, and supplementing the diet with sodium butyrate reduces the concentrations of LPS and proinflammatory cytokines, subsequently attenuating the activation of NF-κB and caspase-3 and eventually inhibiting apoptosis in mammary cells.
Assuntos
Ração Animal/análise , Apoptose , Ácido Butírico/metabolismo , Suplementos Nutricionais/análise , Cabras/metabolismo , Glândulas Mamárias Animais/citologia , Animais , Apoptose/efeitos dos fármacos , Ácido Butírico/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Feminino , Cabras/genética , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Rúmen/efeitos dos fármacos , Rúmen/metabolismoRESUMO
To investigate the effect of sodium butyrate on high-concentrate diet-induced local inflammation of the rumen epithelium, 18 midlactating dairy goats were randomly assigned to 3 groups: a low-concentrate diet group as the control (concentrate:forage = 4:6), a high-concentrate (HC) diet group (concentrate:forage = 6:4), and a sodium butyrate (SB) group (concentrate:forage = 6:4, with 1% SB by weight). The results showed that, with the addition of sodium butyrate, the concentration of lipopolysaccharide (LPS) in rumen fluid (2.62 × 104 ± 2.90 × 103 EU/mL) was significantly lower than that in the HC group (4.03 × 104 ± 2.77 × 103 EU/mL). The protein abundance of pp65, gene expression of proinflammatory cytokines, and activity of myeloperoxidase (MPO) and matrix metalloproteinase (MMP)-2,9 in the rumen epithelium were significantly down-regulated by SB compared with those in the HC group. With sodium butyrate administration, the concentration of NH3-N (19.2 ± 0.890 mM) in the rumen fluid was significantly higher than that for the HC group (12.7 ± 1.38 mM). Severe disruption of the rumen epithelium induced by HC was also ameliorated by dietary SB. Therefore, local inflammation and disruption of the rumen epithelium induced by HC were alleviated with SB administration.
Assuntos
Ração Animal/efeitos adversos , Ácido Butírico/administração & dosagem , Dieta/efeitos adversos , Epitélio/imunologia , Doenças das Cabras/tratamento farmacológico , Rúmen/efeitos dos fármacos , Animais , Citocinas/genética , Citocinas/imunologia , Epitélio/efeitos dos fármacos , Feminino , Doenças das Cabras/imunologia , Doenças das Cabras/metabolismo , Cabras/crescimento & desenvolvimento , Cabras/imunologia , Cabras/metabolismo , Lactação , Rúmen/imunologia , Rúmen/metabolismoRESUMO
OBJECTIVE: To observe the diagnosis and treatment of bone marrow edema syndrome and summarize its features, mechanisms and its differences from avascular necrosis of femoral head. METHODS: From 2004.1, 19 patients (12 patients were males and 7 patients were females, with a mean age of (46.70 +/- 10.36) years) with bone marrow edema syndrome of hip treated with Ibandronate and physical therapy, as well as scored with Harris system before and after treatment. RESULTS: Average score before treatment was (43.17 +/- 12.62), and (86.73 +/- 14.29) after treatment, and the difference was significant (P < 0.05). CONCLUSION: Bone marrow edema syndrome of hip is different from avascular necrosis of the hip, it is a distinct clinical entity.
Assuntos
Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/tratamento farmacológico , Necrose da Cabeça do Fêmur/diagnóstico , Articulação do Quadril/patologia , Adulto , Conservadores da Densidade Óssea/uso terapêutico , Doenças da Medula Óssea/patologia , Doenças da Medula Óssea/terapia , Difosfonatos/uso terapêutico , Feminino , Necrose da Cabeça do Fêmur/patologia , Articulação do Quadril/efeitos dos fármacos , Humanos , Ácido Ibandrônico , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To observe the clinical effect of Astragalus Injection (, AI) and its immuno-regulatory action in treating chronic aplastic anemia (CAA). METHODS: Sixty patients with CAA were randomly assigned to two groups equally, both were treated with Stanozolol three times a day, 2 mg each time through oral intake, but AI was given additionally to the patients in the treated group once a day via intravenous dripping. All were treated for 15 days as one therapeutic course and the whole medication lasted for more than 4 months totally, with follow-up adopted. The clinical efficacy was estimated and the changes of T-lymphocyte subsets in peripheral blood as well as the serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) were observed. RESULTS: The total effective rate in the treated group was 83.3% (25/30), which was higher than that in the control group 66.7% (20/30), showing significant difference between them (P<0.05). Levels of hemoglobin, WBC, reticular cell and platelet were elevated in both groups after treatment, but the improvement was significantly better in the treated group than that in the control group with respect to the former three indexes (P<0.05). The level of CD4(+) increased and that of CD8(+) decreased significantly after treatment in the treated group (P<0.05), which showed significant difference as compared with those in the control group (P<0.05). Levels of serum TNF-alpha and IL-2 lowered after treatment in both groups, but significance only showed in the treated group (P<0.05). The degree of proliferation in bone marrow got raised significantly and the percentage of non-hemopoietic cells reduced significantly in the treated group after treatment, also showing significant difference to those in the control group (P<0.05). CONCLUSION: AI could promote the recovery of hemopoietic function, which might be through improving T-lymphocyte subsets and reducing the release of negative regulatory factors such as TNF-alpha and IL-2 to alleviate the inhibition on hemopoietic function.