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The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.
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INTRODUCTION: Early identification of patients with sepsis at high risk of death remains a challenge, and whether brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a prognostic effect on patients with sepsis is controversial. Here, we clarified the prognostic value of BNP and NT-proBNP and sought to establish suitable cutoff values and intervals. METHODS: We searched five databases to identify studies that met the inclusion criteria. The primary outcomes were the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and corresponding 95% credible interval (95% CI) of BNP and NT-proBNP. The secondary outcomes were the sensitivity and specificity of BNP or NT-proBNP in subgroup analyses. RESULTS: Forty-seven studies were included in our meta-analysis. The pooled sensitivity of NT-proBNP (0.77 [0.68, 0.84]) was weaker than that of BNP (0.82 [0.76, 0.87]), the pooled specificity of NT-proBNP (0.70 [0.60, 0.77]) was less than that of BNP (0.77 [0.71, 0.82]), and the AUC of BNP (0.87 [0.83-0.89]) was greater than that of NT-proBNP (0.80 (0.76-0.83]). The results of the subgroup analysis showed that the cutoff range of 400-800 pg/mL for BNP had high sensitivity (0.86 [0.74-0.98]) and specificity (0.87 [0.81-0.93]) and was probably the most appropriate cutoff range. CONCLUSIONS: Elevated levels of BNP and NT-proBNP were significantly related to the mortality of patients with sepsis and had a moderate prognostic value in predicting the mortality of patients with sepsis. In addition, our meta-analysis preliminarily established appropriate cutoff values for BNP and NT-proBNP.
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Biomarcadores , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Sepse , Humanos , Peptídeo Natriurético Encefálico/sangue , Sepse/mortalidade , Sepse/sangue , Sepse/diagnóstico , Biomarcadores/sangue , Fragmentos de Peptídeos/sangue , Prognóstico , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). METHODS: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Between July 16, 2019, and September 9, 2022, 62 patients (AS, nâ =â 32; AG, nâ =â 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; Pâ =â .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; Pâ <â .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; Pâ =â .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. CONCLUSION: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).
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Our study investigates the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the spl43 mutant. This mutant is characterized by persistent reddish-brown leaf spots from the seedling stage to maturity, leading to extensive leaf necrosis. Using map-based cloning, we localized the responsible locus to a 330 Kb region on chromosome 2. We identified LOC_Os02g56000, named OsRPT5A, as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and the generation of CRISPR/Cas9-mediated knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. The qPCR results from different parts of the rice plant revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by the mutation. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in spl43 mutants by examining the physiological indexes of leaves, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the spl43 mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice pathogen resistance mechanisms. Overall, our results suggest that OsRPT5A plays a critical role in regulating ROS homeostasis and enhancing pathogen resistance in rice.
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Mapeamento Cromossômico , Oryza , Doenças das Plantas , Folhas de Planta , Proteínas de Plantas , Espécies Reativas de Oxigênio , Xanthomonas , Oryza/genética , Oryza/microbiologia , Oryza/metabolismo , Folhas de Planta/genética , Folhas de Planta/microbiologia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Xanthomonas/patogenicidade , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Espécies Reativas de Oxigênio/metabolismo , Resistência à Doença/genética , Mutação , Fenótipo , Regulação da Expressão Gênica de PlantasRESUMO
Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.
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Background: Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. Methods: We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. Results: The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. Conclusion: The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.
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AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.
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Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.
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Globally, most high-grade ores have already been exploited. Contemporary mining tends to focus on the extraction of lower-grade ores thereby leaving large stored tailings open to the environment. As a result, current mines have emerged as hotspots for the migration of metal(loid)s and resistance genes, thereby potentially contributing to a looming public health crisis. Therefore, the management and remediation of tailings are the most challenging issues in environmental ecology. Bioremediation, a cost-effective solution for the treatment of multi-element mixed pollution (co-contamination), shows promise for the restoration of mine tailings. This review focuses on the bioremediation technologies developed to untangle the issues of non-ferrous metal mine tailings. These technologies address the environmental risks of multi-element exposure to the ecosystem and human health risks. It provides a review and comparison of current bioremediation technologies used to mineralize metal(loid)s. The role of plant-microorganisms and their mechanisms in the remediation of tailings are also discussed. The importance of "treating waste with wastes" is crucial for advancing bioremediation technologies. This approach underscores the potential for waste materials to contribute to environmental cleanup processes. The concept of a circular economy is pertinent in this context, emphasizing recycling and reuse. There's an immediate need for international collaboration. Collaboration is needed in policy-making, funding, and data accessibility. Sharing data is essential for the growth of bioremediation globally.
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Biodegradação Ambiental , Metais , Mineração , Humanos , ReciclagemRESUMO
Prior studies indicate that the reaction wave can propagate from the impact surface, but the possibility and the influencing factors of the reaction wave formation are still unclear. This work investigates the propagation behavior of the shock-induced reaction wave for Ni/Al clad particle composites with varying stoichiometry (from 0.5 to 0.75 of the Ni mole fraction) through molecular dynamics simulations. It is found that the solid-state reaction processes with or without wave propagation strongly depend on the conjunction of stoichiometry and shock intensity. Within the cases of wave propagation, the calculated propagation velocity (in the range of 135-170 m/s) increases linearly or exponentially with the Ni mole fraction. Furthermore, the thermodynamic criteria for the reaction wave formation, including Al melting at the collision surface and higher temperature gradient, are established by analysis of the shock-induced high-entropy layer. In addition, microstructural characterization reveals the intrinsic mechanisms of the propagation of the reaction wave and the formation of additional reaction wave, namely, the dissolution of Ni into Al and the coalescence of reaction zones. Apart from the propagation behavior, the initial stoichiometry influences the crystallization-dissolution of B2-NiAl during reaction processes, notably through an exponential growth relationship between maximum crystallinity and the Ni mole fraction. These findings may provide a physical basis for improving traditional reaction rate models to break through phenomenological understanding.
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HD-Zip (Homeodomain-Leucine Zipper) is a family of transcription factors unique to higher plants and plays a vital role in plant growth and development. Increasing research results show that HD-Zip transcription factors are widely involved in many life processes in plants. However, the HD-Zip transcription factor for cannabis, a valuable crop, has not yet been identified. The sequence characteristics, chromosome localization, system evolution, conservative motif, gene structure, and gene expression of the HD-Zip transcription factor in the cannabis genome were systematically studied. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify its function. The results showed that cannabis contained 33 HD-Zip gene members. The number of amino acids is 136-849aa, the isoelectric point is 4.54-9.04, and the molecular weight is 23264.32-93147.87Da. Many cis-acting elements are corresponding to hormone and abiotic stress in the HD-Zip family promoter area of cannabis. Sequencing of the transcriptome at 5 tissue sites of hemp, stems, leaves, bracts, and seeds showed similar levels of expression of 33 members of the HD-Zip gene family at 5 tissue sites. Bioinformatics results show that HD-Zip expression is tissue-specific and may be influenced by hormones and environmental factors. This lays a foundation for further research on the gene function of HD-Zip.
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MAIN CONCLUSION: A stable genetic transformation system for Erigeron breviscapus was developed. We cloned the EbYUC2 gene and genetically transformed it into Arabidopsis thaliana and E. breviscapus. The leaf number, YUC2 gene expression, and the endogenous auxin content in transgenic plants were significantly increased. Erigeron breviscapus is a prescription drug for the clinical treatment of cardiovascular and cerebrovascular diseases. The rosette leaves have the highest content of the major active compound scutellarin and are an important component in the yield of E. breviscapus. However, little is known about the genes related to the leaf number and flowering time of E. breviscapus. In our previous study, we identified three candidate genes related to the leaf number and flowering of E. breviscapus by combining resequencing data and genome-wide association study (GWAS). However, their specific functions remain to be characterized. In this study, we cloned and transformed the previously identified full-length EbYUC2 gene into Arabidopsis thaliana, developed the first stable genetic transformation system for E. breviscapus, and obtained the transgenic plants overexpressing EbYUC2. Compared with wild-type plants, the transgenic plants showed a significant increase in the number of leaves, which was correlated with the increased expression of EbYUC2. Consistently, the endogenous auxin content, particularly indole-3-acetic acid, in transgenic plants was also significantly increased. These results suggest that EbYUC2 may control the leaf number by regulating auxin biosynthesis, thereby laying a foundation for revealing the molecular mechanism governing the leaf number and flowering time of E. breviscapus.
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Arabidopsis , Erigeron , Erigeron/genética , Arabidopsis/genética , Estudo de Associação Genômica Ampla , Ácidos Indolacéticos , Folhas de Planta/genética , Plantas Geneticamente Modificadas , Transformação GenéticaRESUMO
Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on-target off-tumor toxicity limits Ab-based therapeutics. Cluster of differentiation 147 (CD147) is a tumor-associated membrane antigen overexpressed in cancer cells. Ab-based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia-activation strategies, we developed a conditional Ab-dependent cellular cytotoxicity (ADCC)-enhanced humanized anti-CD147 Ab, HcHAb18-azo-PEG5000 (HAP18). Afucosylated ADCC-enhanced HcHAb18 Ab was produced by a fed-batch cell culture system. Azobenzene (Azo)-linked PEG5000 conjugation endowed HAP18 Ab with features of hypoxia-responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement-dependent cytotoxicity, and Ab-dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor-inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia-activated ADCC-enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti-CD147 Ab drugs.
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Postoperative cognitive dysfunction (POCD) remains a major issue that worsens the prognosis of elderly surgery patients. This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients, aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols, ultimately reducing the incidence of POCD in elderly surgery patients.
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Anestesia , Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Humanos , Idoso , Complicações Cognitivas Pós-Operatórias/induzido quimicamente , Complicações Cognitivas Pós-Operatórias/epidemiologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Anestesia/efeitos adversos , Anestésicos IntravenososRESUMO
Environmental stress at high altitudes drives the development of distinct adaptive mechanisms in plants. However, studies exploring the genetic adaptive mechanisms of high-altitude plant species are scarce. In the present study, we explored the high-altitude adaptive mechanisms of plants in the Himalayas through whole-genome resequencing. We studied two widespread members of the Himalayan endemic alpine genus Roscoea (Zingiberaceae): R. alpina (a selfing species) and R. purpurea (an outcrossing species). These species are distributed widely in the Himalayas with distinct non-overlapping altitude distributions; R. alpina is distributed at higher elevations, and R. purpurea occurs at lower elevations. Compared to R. purpurea, R. alpina exhibited higher levels of linkage disequilibrium, Tajima's D, and inbreeding coefficient, as well as lower recombination rates and genetic diversity. Approximately 96.3% of the genes in the reference genome underwent significant genetic divergence (FST ≥ 0.25). We reported 58 completely divergent genes (FST = 1), of which only 17 genes were annotated with specific functions. The functions of these genes were primarily related to adapting to the specific characteristics of high-altitude environments. Our findings provide novel insights into how evolutionary innovations promote the adaptation of mountain alpine species to high altitudes and harsh habitats.
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Altitude , Zingiberaceae , Himalaia , Genômica , Evolução Biológica , Adaptação Fisiológica/genéticaRESUMO
Aster tataricus L.f. is highly valued for its rich reserves of bioactive compounds. Our research focused on the identification of previously unreported compounds found within the ethanol extract of A. tataricus. Through meticulous spectroscopic analyses and computational methods like NMR calculations and ECD, we successfully elucidated the structures of five novel compounds termed tatarisides A-E (1-5), alongside two known compounds (6, 7). The anti-inflammatory assays conducted yielded noteworthy results, particularly in relation to compounds 1 and 5. These compounds exhibited significant potential in inhibiting the release of NO in LPS-induced RAW 264.7 cells, as evidenced by their respective IC50 values of 17.81 ± 1.25 µM and 13.32 ± 0.84 µM. The discovery of these new compounds adds to the existing knowledge of A. tataricus's chemical composition and potential applications.
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Aster , Estrutura Molecular , Aster/química , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , EtanolRESUMO
Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.
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Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Sepse , Animais , Sepse/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Ratos , Administração IntravenosaRESUMO
Objective: Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that can develop after experiencing or witnessing a traumatic event. Exposure therapy is a common treatment for PTSD, but it has varying levels of efficacy depending on sex. In this study, we aimed to compare the sexual dimorphism in brain activation during the extinction of fear conditioning in male and female rats by detecting the c-fos levels in the whole brain. Methods: Thirty-two rats (Male: n = 16; Female: n = 16) were randomly separated into the extinction group as well as the non-extinction group, and fear conditioning was followed by extinction and non-extinction, respectively. Subsequently, brain sections from the sacrificed animal were performed immunofluorescence and the collected data were analyzed by repeated two-way ANOVAs as well as Pearson Correlation Coefficient. Results: Our findings showed that most brain areas activated during extinction were similar in both male and female rats, except for the reuniens thalamic nucleus and ventral hippocampi. Furthermore, we found differences in the correlation between c-fos activation levels and freezing behavior during extinction between male and female rats. Specifically, in male rats, c-fos activation in the anterior cingulate cortex was negatively correlated with the freezing level, while c-fos activation in the retrosplenial granular cortex was positively correlated with the freezing level; but in female rats did not exhibit any correlation between c-fos activation and freezing level. Finally, the functional connectivity analysis revealed differences in the neural networks involved in extinction learning between male and female rats. In male rats, the infralimbic cortex and insular cortex, anterior cingulate cortex and retrosplenial granular cortex, and dorsal dentate gyrus and dCA3 were strongly correlated after extinction. In female rats, prelimbic cortex and basolateral amygdala, insular cortex and dCA3, and anterior cingulate cortex and dCA1 were significantly correlated. Conclusion: These results suggest divergent neural networks involved in extinction learning in male and female rats and provide a clue for improving the clinical treatment of exposure therapy based on the sexual difference.
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BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare highly heterogeneous disease. In this paper, we present a case of NIID featured in cortical involvement in left hemisphere of brain and the imaging changes in the process of the disease. CASE PRESENTATION: A 57-year-old female was hospitalized due to recurrent attacks of headache with cognitive impairment and tremor for 2 years. The symptoms of headache episodes were reversible. The characteristic radiologic change was high intensity signal involving the grey matter-white matter junction on the brain diffusion-weighted imaging (DWI), which existed in the frontal lobe and then extended backwards. Atypical features on fluid-attenuated inversion recovery (FLAIR) sequences showing small patchy high signals in the cerebellar vermis. High signals and edema were detected on FLAIR images along the cortex of the left occipito-parieto-temporal lobes, expanding and gradually shrinking in the follow-up visit. Besides, cerebral atrophy and bilateral symmetrical leukoencephalopathy were also detected. Skin biopsy and genetic testing confirmed the diagnosis of NIID. CONCLUSION: Except for typical radiological change strongly suggesting NIID, it is also necessary to notice the insidious symptoms of NIID combining with some atypical imaging features to make an early diagnosis. Skin biopsies or genetic testing should be carried out early in patients with highly suspected NIID.
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Doenças Neurodegenerativas , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/patologia , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , CefaleiaRESUMO
BACKGROUND: Previous studies of brown planthopper (BPH), Nilaparvata lugens, showed that carrying the plant pathogenic virus, rice ragged stunt virus (RRSV), enhanced the lethality of the entomopathogenic fungus, Metarhizium anisopliae (YTTR). The underlying mechanism for this was not established but a serine protease cascade was hypothesized to be involved. RESULTS: Two immune response genes, NlKPI and NlVenomase, were identified and shown to be involved. The synthesized double-strand RNA (dsRNA) techniques used in this study to explore gene function revealed that treatment with dsRNA to silence either gene led to a higher BPH mortality from M. anisopliae infection than the dsRNA control treatment. NlKPI and NlVenomase play vital roles in BPH immunity to defend against alien pathogens. Both genes participate in the immune response process of BPH against co-infection with RRSV and M. anisopliae YTTR by regulating the expression of antimicrobial peptides and phenoloxidase activity. CONCLUSION: Our study provided new targets for BPH biocontrol and laid a solid foundation for further research on the interaction of virus-insect-EPF (entomopathogenic fungus). © 2023 Society of Chemical Industry.