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1.
Food Chem ; 400: 133961, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36084584

RESUMO

The broad application prospect of fish gelatin makes the traceability and identification of fish gelatin imminent. High performance liquid chromatography and high-resolution mass spectrometry (HPLC-MS/MS) was used to identify fish gelatins in seven commercial cyprinid fishes, namely, black carp, grass carp, silver carp, bighead carp, common carp, crucian carp, and Wuchang bream. By comparison with theoretical mammalian collagen (bovine and porcine collagen), the common and unique theoretical peptides were found in the collagen of grass carp, silver carp, and crucian carp, respectively. HPLC-MS/MS results showed that 7 common characteristic peptides were obtained from seven cyprinid fish gelatins. Moreover, 44, 36, and 42 unique characteristic peptides were detected in the gelatins of grass carp, silver carp, and crucian carp, respectively. The combined use of common and unique characteristic peptides could improve the accuracy and authenticity of traceability and identification of fish gelatin in comparison with mammalian gelatin.


Assuntos
Carpas , Gelatina , Animais , Bovinos , Cromatografia Líquida de Alta Pressão , Colágeno , Peixes , Gelatina/química , Mamíferos , Suínos , Espectrometria de Massas em Tandem
2.
Food Chem ; 400: 134092, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36084600

RESUMO

Chiral analysis of food components can provide important information for food quality, bioactivity and safety. Determination of enantiomeric ratios in food is a tedious task, due to the poor resolution and insufficient sensitivity for simultaneous discrimination and quantification of trace amounts of d-form metabolites. Herein, a high-throughput, high-sensitive and high-resolution method was developed for simultaneously determining enantiomeric ratios of multiple chiral α-hydroxy/amino acids (HA/AAs) from fermented milks in one-run by [d0]/[d5]-estradiol-3-benzoate-17ß-chloroformate labeling-assisted ion mobility - mass spectrometry. Results revealed extensive variation in chiral HA/AA profiles among 15 fermented milks. A total of 14 D-HA/AAs were identified. d-Lactic acid and d-alanine appeared as the most discriminatory in fermented milks with live lactic acid bacteria (LAB). Results suggested that glycolysis, casein hydrolysis and enantioisomerization of HA/AAs were most likely affected by various starter culture LAB. It may contribute to entail a valuable step forward in food quality control and discovering functional-related chiral biomarkers.


Assuntos
Aminoácidos , Caseínas , Alanina/análise , Aminoácidos/análise , Animais , Benzoatos/análise , Caseínas/análise , Estradiol/análise , Hidroxiácidos/análise , Ácido Láctico/análise , Espectrometria de Massas/métodos , Leite/química , Estereoisomerismo
3.
Bioact Mater ; 20: 528-538, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35846840

RESUMO

In this study, a novel artificial intervertebral disc implant with modified "Bucklicrystal" structure was designed and 3D printed using thermoplastic polyurethane. The new implant has a unique auxetic structure with building blocks joined "face-to-face". The accompanied negative Poisson's ratio enables its excellent energy absorption and stability under compression. The deformation and load distribution behavior of the implant under various loading conditions (bending, torsion, extension and flexion) has been thoroughly evaluated through finite element method. Results show that, compared to natural intervertebral disc and conventional 3D implant, our new implant exhibits more effective stress transfer and attenuation under practical loading conditions. The implant's ability to contract laterally under compression can be potentially used to alleviate the symptoms of lumbar disc herniation. Finally, the biocompatibility of the implant was assessed in vitro and its ability to restore the physiological function of the disc segment was validated in vivo using an animal model.

4.
Front Pediatr ; 10: 997274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090575

RESUMO

Background: Spastic paraplegia type 54 (SPG54) is a rare inherited autosomal recessive disorder, and a complex hereditary spastic paraplegia (HSP) caused by mutations in the phospholipase DDHD2 gene. SPG54 is characterized by early onset of spastic paraplegia, intellectual disability and dysplasia of corpus callosum. Case presentation: We report a 9 years and 5 months old Chinese girl with progressive spasm of the lower limbs, muscle weakness and intellectual disability. Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia and thinning of the corpus callosum. According to the Wechsler Intelligence Scale, her IQ is 42. By whole exome sequencing, novel compound heterozygous missense mutations in the DDHD2 gene [c.168G>C, p.(Trp56Cys) and c.1505T>C, p.(Phe502Ser)] were identified in the proband. Comparative amino acid sequence alignment across different species revealed that Trp56 and Phe502 in the DDHD2 protein were highly conserved during evolution. And multiple in silico prediction tools suggested that both mutations were deleterious. Conclusions: Our study reports a very rare case of complicated HSP caused by two novel compound heterozygous mutations in the DDHD2 gene. Our findings expand the genetic spectrum of SPG54.

5.
J Diabetes Res ; 2022: 2545476, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090589

RESUMO

Traditional Chinese medicine (TCM) has long been used to treat diabetes mellitus and angina. It has also gained widespread clinical applications in China as a common adjuvant treatment. Although there is high-quality evidence that TCM is effective in regulating glucose and lipid metabolism, the cardiovascular protective effect of TCM in the treatment of diabetes mellitus has not been fully elucidated, especially in patients with both diabetes mellitus and coronary heart disease (CHD). We systematically assessed the efficacy and safety of TCM for the adjuvant treatment of patients with CHD and diabetes mellitus and examined the pharmacological effects and potential mechanisms of TCM medication/herbs on diabetes mellitus with CHD. We found that TCM could improve the control effect of conventional treatment on cardiac function, hemorheology, blood glucose, blood lipid, and inflammation, thus reducing the frequency of angina and the incidence of cardiovascular events and all-cause mortality. These findings indicate that TCM may be used as a complementary approach for patients with diabetes mellitus and CHD. Nevertheless, more rigorously designed randomized controlled trials and long-term evaluations are needed to support these findings.


Assuntos
Doença das Coronárias , Diabetes Mellitus , Glicemia , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Humanos , Incidência , Medicina Tradicional Chinesa
6.
Indian J Dermatol ; 67(2): 208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092214
8.
J Gastrointest Oncol ; 13(4): 1753-1760, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092331

RESUMO

Background: The recurrence of polyps after endoscopic treatment is a difficult problem and there may be an association between blood lipid levels and colorectal polyps, but this is controversial and the aim of this study is to explore the risk factors for colorectal polyp recurrence. Methods: A total of 357 patients who underwent intestinal polypectomy from January 1, 2019 to June 1, 2020 in Sichuan Provincial People's Hospital were included in this retrospective study to analyze the potential association between blood indices and recurrence risk. Polyp recurrence was defined as the detection of 1 or more polyps at any time after polypectomy, regardless of site. Follow-up was performed through the electronic medical record system. Patients' age, gender, tobacco and alcohol liking, duration of follow-up, body mass index (BMI), polyp size, number, type of pathology, and lipid profiles (triglycerides, cholesterol, apolipoprotein B, and apolipoprotein A) were collected. Results: Triglycerides (1.54±0.95 vs. 1.25±1.01, P=0.036) and apolipoprotein B (0.87±0.26 vs. 0.79±0.16 mL, P=0.001) were significantly different in both the recurrence and non-recurrence groups. Binary logistic regression identified 3 independent risk factors for recurrence: triglycerides [odds ratio (OR): 1.763, 95% confidence interval (CI): 1.003 to 3.098, P=0.049], apolipoprotein B (OR: 5.438, 95% CI: 1.411 to 20.961, P=0.014), and the number of polyps (OR: 2.540, 95% CI: 1.649 to 3.911, P<0.001). Conclusions: High levels of triglycerides, apolipoprotein B, and the number of colorectal polyps are risk factors for colorectal polyp recurrence after endoscopic resection. Therefore, for patients at high risk of polyp recurrence, we recommend aggressive control of triglyceride and apolipoprotein B levels.

9.
Med Biol Eng Comput ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36097237

RESUMO

In medicine, identifying the indirect immunofluorescence of human epithelial type 2 (HEp-2) cells plays a decisive role in the diagnosis of autoimmune diseases. The manual interpretation of Hep-2 cell images may lead to some limitations, such as subjectivity, inconsistency and low efficiency. Therefore, it is very important to automatically identify HEp-2 images. Inspired by the outstanding performance of neural networks in image classification tasks, we propose a multi-class and multiple-binary classifier (MCMBC) for the classification of HEp-2 cells. MCMBC is an ensemble learner that contains two kinds of sub-classifiers: multi-class (MC) and multiple-binary (MB). The MC sub-classifier adopts a multi-scale convolutional neural network (MSCNN) that increases the efficiency of information transmission between layers. On the basis of classification results of the MC sub-classifier on validation sets, we can find easy-to-confuse class pairs. An easy-to-confuse class pair is two classes that are not easy to be identified from each other. The MB sub-classifiers adopt multiple-binary pre-trained VGG16 networks that are used to deal with these class pairs. The final prediction for a sample possibly belonging to an easy-to-confuse class is decided by the assembled features extracted from the last fully connected layer of MC and the output of MB sub-classifiers. To evaluate the proposed model, experiments were conducted on the ICPR 2014 Task-2 dataset. Experimental results show that MCMBC performs better than the state-of-the-art method (84.68% vs. 83.35% on the criterion of average classification accuracy (ACA) and 82.89% vs. 82.67% on the criterion of mean classification accuracy (MCA)).

10.
Artigo em Inglês | MEDLINE | ID: mdl-36098495

RESUMO

Solar-driven overall water splitting is an ideal way to generate renewable energy while still challenging. For the first time, this work combined covalent organic frameworks (COFs) and piezoelectric material by covalent linkages to form Z-scheme core@shell heterostructure for overall water splitting. Benefiting from the synergistic effect between the polarized electric field and photo-generated charges, as well as the precise adjustment of shell thickness, the carrier separation and utilization efficiency is greatly improved. The optimal BiFeO3@TpPa-1-COF photocatalyst revealed hydrogen (H2) and oxygen (O2) production rates of 1416.4 and 708.2 µmol·h-1·g-1 under the excitation of ultrasonication coupled with light irradiation, which is the best performance among various piezo- and COF-based photocatalysts. This provides a new sight for the practical application of highly efficient photocatalytic overall water splitting.

11.
Cancer Res ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098964

RESUMO

Menin is necessary for the formation of the menin/MLL complex and is recruited directly to chromatin. Menin is an important tumor suppressor in several cancer types, including lung cancer. Here, we investigated the role of MLL in menin-regulated lung tumorigenesis. Ablation of MLL suppressed KrasG12D-induced lung tumorigenesis in a genetically-engineered mouse model. MLL deficiency decreased histone H3 lysine 4 trimethylation (H3K4me3) and subsequently suppressed expression of the Ras protein-specific guanine nucleotide-releasing factor 1 (Rasgrf1) gene. Rasgrf1 was essential for the GTP-bound active state of Kras and the activation of Kras downstream pathways as well as their cancer-promoting activities. MI-3, a small molecule inhibitor targeting MLL, specifically inhibited the growth of Kras-mutated lung cancer cells in vitro and in vivo with minimal effect on wild-type Kras lung cancer growth. Together, these results demonstrate a novel tumor promoter function of MLL in mutant Kras-induced lung tumorigenesis and further indicate that specific blockade of the MLL-Rasgrf1 pathway may be a potential therapeutic strategy for the treatment of tumors containing Kras mutations.

12.
J Adv Res ; 40: 109-124, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36100320

RESUMO

INTRODUCTION: Immunochemotherapy using PD-1/PD-L1 antibodies in combination with chemotherapeutic agents has become a mainstream treatment for cancer patients, but it remains unclear which drug combinations would produce best therapeutic outcome. OBJECTIVES: The purpose of this study was to investigate two common chemotherapeutic drugs, gemcitabine and cisplatin, for their impacts on the therapeutic efficacy of PD-1 antibody in K-ras-driven cancers known to overexpress PD-L1. METHODS: Both in vitro assays and syngeneic mouse tumor models were used in this study. Biochemical and molecular assays were used to determine the effects of drugs on T cell functions in cell culture models and in mouse/human tumor tissues. Allograft tumor models with K-ras mutation were used to investigate the combination effect of gemcitabine or cisplatin with immunotherapy. Data of lung cancer patients with K-ras mutation treated with cisplatin and toripalimab were analyzed to evaluate the clinical relevance of the lab findings. RESULTS: Cisplatin and gemcitabine unexpectedly exert opposite effect on the therapeutic activity of PD-1 antibody in vivo. Gemcitabine antagonizes the therapeutic effect of PD-1 antibody due to its significant inhibition on CD8+ T cell infiltration, which was observed both in mouse tumor allografts and in human pancreatic cancer tissues. In contrast, cisplatin shows synergistic activity with PD-1 antibody by activation of CD8+ T cells through the DNA damage-mediated cGAS-STING sensing mechanism, leading to increase of T cell infiltration and secretion of antitumor cytokines. Clinical data show that a combination of cisplatin with PD-1 antibody toripalimab could be effective in advanced lung cancer patients with K-ras mutation who failed prior therapies. CONCLUSIONS: Our study shows that a key factor in selecting chemotherapeutic agents for immunochemotherapy is the drug's impact on T cell functions, and that cisplatin-based chemotherapy is an excellent choice for combination with immune checkpoint antibody to achieve favorable clinical outcome.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Animais , Antineoplásicos/farmacologia , Antígeno B7-H1 , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Humanos , Fatores Imunológicos/farmacologia , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Receptor de Morte Celular Programada 1
13.
Shanghai Kou Qiang Yi Xue ; 31(2): 178-183, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-36110076

RESUMO

PURPOSE: To detect the level of B cell activating factor (B - cell activating factor of the TNF family, BAFF) in the serum of patientes suffering from systemic lupus erythematosus (SLE) with periodontitis, and analyze the relationship between the expression of BAFF with periodontitis and SLE. METHODS: According to the inclusion criteria, patients visiting the Department of Stomatology and Rheumatology, Shengjing Hospital Affiliated to China Medical University were selected, including 19 patients in the periodontitis group(P group), 22 in the systemic lupus erythematosus group (SLE group), 24 in the systemic lupus erythematosus combined with periodontitis group(SLE+P group), and 20 in the healthy control group(H group). The general information, periodontal probing depth (PD), clinical attachment loss (CAL), gingival sulcus bleeding index(SBI) were collected. Serum samples of patients in each group were collected, and BAFF content was determined by Elisa. Rheumatic and immunological indexes of subjects in SLE group and SLE+P group were determined, and the correlation between BAFF content and periodontal indexes was analyzed. SPSS 20.0 software package was used for statistical analysis. RESULTS: CAL in P+SLE group was significantly higher than that in P group(P<0.05). Serum BAFF concentrations in SLE+P group, SLE group and P group were significantly higher than those in the healthy control group (P<0.05). Serum BAFF concentration in SLE+P group was significantly higher than that in SLE group(P<0.05). ESR, SLEDAI and disease duration in SLE+P group were significantly higher than those in SLE group (P<0.05). The expression level of BAFF in serum was positively correlated with CAL and SBI(P<0.01). The expression level of BAFF in serum was positively correlated with PD(P<0.05). There was significant positive correlation between serum BAFF level and duration of disease and hormone use(P<0.01). Serum BAFF level was positively correlated with C3 (P<0.05). CONCLUSIONS: SLE has certain correlation with periodontitis, and serum BAFF in SLE patients with periodontitis is significantly increased.BAFF may be associated with the development of SLE and periodontitis.


Assuntos
Lúpus Eritematoso Sistêmico , Periodontite , Fator Ativador de Células B , Ensaio de Imunoadsorção Enzimática , Hormônios , Humanos
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(9): 994-1000, 2022.
Artigo em Chinês | MEDLINE | ID: mdl-36111717

RESUMO

OBJECTIVES: To study the changes in the mortality rate and cause of death of hospitalized neonates in grade A tertiary hospitals in Weifang City of Shandong Province during a 10-year period. METHODS: A retrospective analysis was performed on 461 neonates who died in three grade A tertiary hospitals in Weifang City of Shandong Province from January 1, 2012 to December 31, 2021. The related clinical data were collected to examine the changes of neonatal mortality with time, gestational age (GA) and birth weight (BW). The main causes of death of the neonates were compared between the first 5 years (2012-2016) and the last 5 years (2017-2021) in the period. RESULTS: A total of 43 037 neonates were admitted from 2012 to 2021, among whom 461 died, resulting in a mortality rate of 1.07%. The mortality rate in the last 5 years was significantly lower than that in the first 5 years [0.96% (211/22 059 vs 1.19% (250/20 978); P<0.05]. The mortality rate of neonates decreased with the increases in GA and BW (P<0.05). In the first 5 years, the top three main causes of neonatal death were respiratory distress syndrome (RDS), sepsis, and pneumorrhagia, while in the last 5 years, the top three causes were sepsis, pneumorrhagia, and RDS. The leading cause of death was severe asphyxia for the neonates with a GA of <26 weeks and a BW of <750 g in both the first and last 5 years. For the neonates with a GA of 26-<28 weeks, the leading cause of death changed from RDS in the first 5 years to pneumorrhagia in the last 5 years. For the neonates with a BW of 750-<1 000 g, the leading cause of death changed from pneumorrhagia in the first 5 years to RDS in the last 5 years. For the neonates with a GA of 28-<32 weeks and a BW of 1 000-<1 500 g, the leading cause of death was RDS in both the first and last 5 years. For the neonates with a GA of 32-<37 weeks and a BW of 1 500-<2 500 g, the leading cause of death changed from RDS in the first 5 years to sepsis in the last 5 years. The leading cause of death was sepsis for the neonates with a GA of 37-<42 weeks and a BW of 2 500-<4 000 g in both the first and last 5 years. CONCLUSIONS: The mortality rate of neonates in the grade A tertiary hospitals in Weifang City of Shandong Province has been decreasing in the past 10 years, and it decreases with the increases in GA and BW. Sepsis, RDS, and pneumorrhagia are the leading causes of neonatal death. The mortality rate caused by RDS decreases from the first 5 years to the last 5 years, while the mortality rate caused by sepsis or pneumorrhagia increases from the first 5 years to the last 5 years. Therefore, reducing the incidence rates of sepsis, RDS, and pneumorrhagia is the key to reducing neonatal mortality.


Assuntos
Morte Perinatal , Síndrome do Desconforto Respiratório do Recém-Nascido , Sepse , Peso ao Nascer , Causas de Morte , Feminino , Humanos , Recém-Nascido , Estudos Retrospectivos
15.
J Hazard Mater ; 441: 129945, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36113345

RESUMO

Given the large amount of toxic Cr(VI) wastewater from various industries, it is urgent to take effective treatment measures. Adsorption has been regarded as highly desirable for Cr(VI) removal, but the effectiveness of most adsorbents is significantly dependent on pH value, in which precipitous performance drop and even structural collapse generally occur in strong acidic/alkaline aqueous. Thus, maintaining high adsorption performance and structural integrity over a wide pH range is challenging. To efficiently remove Cr(VI), we designed and prepared of an acid-base resistant metal-organic framework (MOF) Zr-BDPO, by introducing weak acid-base groups (-NH-, -N= and -OH) onto the ligand. Zr-BDPO achieved a maximum adsorption capacity of 555.6 mg·g-1 and retained skeletal structure at pH= 1-11. Interestingly, all these groups can generate conjugate acid-base pairs by means of H+ and OH- in the external solution and then form buffer layer. The removal of Cr(VI) at a broad range of pH values primarily via hydrogen bonds between -NH- and -OH, and the oxoanion species of Cr(VI) is unusual. This strategy that insulating high concentrations of acids and bases and relying on hydrogen bonds to capture Cr(VI) oxoanions provides a new perspective for actual Cr(VI) wastewater treatment.

16.
Sci Total Environ ; : 158819, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36116661

RESUMO

Increasingly drastic global change is expected to cause hydroclimatic changes, which will influence vegetation productivity and pose a threat to the terrestrial carbon sink. Asymmetry represents an imbalance between vegetation growth and loss of growth during dry and wet periods, respectively. However, the mechanisms of asymmetric plant responses to hydrological changes remain poorly understood. Here, we examined the spatiotemporal patterns of asymmetric responses of vegetation productivity across terrestrial ecosystems in China. We analyzed several observational and satellite-based datasets of plant productivity and several reanalyzed datasets of hydroclimatic variables from 2001 to 2020, and used a random forest model to assess the importance of hydroclimatic variables for these responses. Our results showed that the productivity of >50 % of China's vegetated areas showed a more positive asymmetry (2.3 ±â€¯9.4 %) over the study period, which were distributed broadly in northwest China (mainly grasslands and sparse vegetation ecosystems). Negative asymmetries were most common in forest ecosystems in northeast China. We demonstrated that one-third of vegetated areas tended to exhibit significant changes in asymmetry during 2001-2020. The trend towards stronger positive asymmetry (0.95 % yr-1) was higher than that towards stronger negative asymmetry (-0.55 % yr-1), which is beneficial for the carbon sink. We further showed that in China, soil moisture was a more important driver of spatiotemporal changes in asymmetric productivity than precipitation. We identified thresholds of surface soil moisture (20-30 %, volume water content) and root-zone soil moisture (200-350 mm, equivalent water height) that were associated with changes in asymmetry. Our findings highlight the necessity of considering the dynamic responses of vegetation to hydrological factors in order to fully understand the physiological growth processes of plants and avoid the possible loss of productivity due to future climate change.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36117387

RESUMO

T lymphocytes (T cells) are essential for tumor immunotherapy. However, the insufficient number of activated T cells greatly limits the efficacy of tumor immunotherapy. Herein, we proposed an oncolytic virus-mimicking strategy to enhance T cell recruitment and activation for tumor treatment. We constructed an oncolytic virus-like nanoplatform (PolyIC@ZIF-8) that was degraded in the acidic tumor environment to release PolyIC and Zn2 +. The released PolyIC exhibited an oncolytic virus-like function that induced tumor cell apoptosis and promoted T cell recruitment and activation through a tumor antigen-dependent manner. More importantly, the released Zn2+ not only enhanced T cell recruitment by inducing CXCL9/10/11 expression but also promoted T cell activation to increase interferon-γ (INF-γ) expression by i nducing the phosphorylation of ZAP-70 via a tumor antigen-independent manner. This Zn2+-enhanced oncolytic virus-mimicking strategy provides a new approach for tumor immunotherapy .

18.
J Neurosci ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127134

RESUMO

The chromatin remodeler CHD8 represents a high-confidence risk factor in autism, a multistage progressive neurological disorder, however the underlying stage-specific functions remain elusive. In this study, by analyzing Chd8 conditional knockout mice (male and female), we find that CHD8 controls cortical neural stem/progenitor cell (NSC) proliferation and survival in a stage-dependent manner. Strikingly, inducible genetic deletion reveals that CHD8 is required for the production and fitness of transit-amplifying intermediate progenitors (IPCs) essential for upper-layer neuron expansion in the embryonic cortex. p53 loss-of-function partially rescue apoptosis and neurogenesis defects in the Chd8-deficient brain. Further, transcriptomic and epigenomic profiling indicates that CHD8 regulates the chromatin accessibility landscape to activate neurogenesis-promoting factors including TBR2, a key regulator of IPC neurogenesis, while repressing DNA damage- and p53-induced apoptotic programs. In the adult brain, CHD8 depletion impairs forebrain neurogenesis by impeding IPC differentiation from NSCs in both subventricular and subgranular zones, however, unlike in embryos, it does not affect NSC proliferation and survival. Treatment with an FDA-approved antidepressant fluoxetine partially restores adult hippocampal neurogenesis in Chd8-ablated mice. Together, our multistage functional studies identify temporally-specific roles for CHD8 in developmental and adult neurogenesis, pointing to a potential strategy to enhance neurogenesis in the CHD8-deficient brain.SIGNIFICANCE STATEMENT:The role of the high-confidence autism gene CHD8 in neurogenesis remains incompletely understood. Here, we identify a stage-specific function of CHD8 in development of neural stem/progenitors (NSC) in developing and adult brains by conserved, yet spatiotemporally distinct, mechanisms. In embryonic cortex, CHD8 is critical for the proliferation, survival, and differentiation of both NSC and intermediate progenitors (IPC) during cortical neurogenesis. In adult brain, CHD8 is required for IPC generation but not the proliferation and survival of adult NSCs. Treatment with an FDA approved antidepressant fluoxetine partially rescues the adult neurogenesis defects in CHD8-mutants. Thus, our findings help resolve CHD8 functions throughout life during embryonic and adult neurogenesis, and point to a potential avenue to promote neurogenesis in CHD8 deficiency.

19.
Cancer Med ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127626

RESUMO

OBJECTIVE: Despite the availability of new agents, elderly patients with multiple myeloma (MM) usually present with poor outcomes due to the heterogeneity of disease conditions, especially immune deficiency. Regulatory B cells (Bregs) can be involved in immune defects by exerting immune regulatory functions in MM. In order to provide more evidence-based practice for the elderly MM, the study established and assessed a stratified therapeutic model with studies on Bregs for Chinese Elderly Multiple Myeloma in 2021 (CEMM2021). METHODS: In this open-label, non-interventional, prospective study in the real world, 159 newly diagnosed MM (NDMM) patients over 65 years old were sequentially recruited and bone marrow aspirates prior to treatment were obtained to detect the ratios of Bregs by flow cytometry. RESULTS: Based on the CEMM2021 model, 147 patients had received at least one cycle of induction therapy, including bortezomib/dexamethasone (Bd) (n = 80), lenalidomide/dexamethasone (Rd) (n = 27), Bd with a third agent X (Bd + X) (n = 27), and other regimens (n = 13). The proportions of patients achieving very good partial response or better were comparable among Bd, Bd + X, and Rd groups (41.9% vs. 54.5% vs. 44.0%, p = 0.472). Besides, the progression-free survival (PFS) and overall survival (OS) were not significantly different among Rd, Bd, and Bd + X groups. Multivariable analysis showed that induction efficacy less than partial response (PR) were poor prognostic factors for PFS, while Revised-International Staging System (R-ISS) III and efficacy less than PR were poor prognostic factors for OS. This study also found that the ratios of bone marrow Bregs <10% (p = 0.036) and SUVmax of PET-CT scan >4.2 (p = 0.000) were closely correlated with OS in the elderly MM. CONCLUSIONS: For the elderly NDMM, the CEMM2021 algorithm in our center might provide a valuable reference for the guidance of therapeutic strategies, with the combination of Bregs resulting in an effective and clinically meaningful prediction in contemporary treatment.

20.
Front Pharmacol ; 13: 974995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120312

RESUMO

Objective: To evaluate the efficacy and safety of Zhibitai (ZBT) in the treatment of patients with hyperlipidemia (HLP). Methods: A search of 8 electronic databases was conducted to find randomized controlled trials (RCTs), to evaluate the efficacy and safety of ZBT for the treatment of HLP. The risk of bias in randomized controlled trials was assessed by using the Cochrane Collaboration Risk of Bias tool for randomized controlled trials 2.0 (RoB 2.0). The primary outcomes were the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The total effective rate served as the secondary outcome. The incidence of adverse events was considered the safety outcome. Review Manager 5.4 was used to conduct meta-analyses. Data were pooled by random-effects or fixed-effects model to obtain the mean difference (MD), risk ratio (RR), odds ratio (OR), and 95% confidence interval (CI). Results: There were 28 eligible RCTs with a total of 2,952 participants. Overall, we verified that ZBT plus conventional therapy (CT) was superior to CT for the treatment of HLP [TC: MD = -0.50, 95% CI (-0.80, -0.19); TG: MD = -0.38, 95% CI (-0.49, -0.27); LDL-C: MD = -0.50, 95% CI (-0.69, -0.31); HDL-C: MD = 0.17, 95% CI (0.11, 0.24); total effective rate: OR = 4.26, 95% CI (2.28, 7.95)]. There were no significant differences in the primary outcomes between ZBT alone vs. CT (p > 0.05). For safety, the ZBT group (with CT or alone) outperformed the CT group [ZBT alone: RR = 0.51, 95% CI (0.32, 0.81); ZBT plus CT: RR = 0.51, 95% CI (0.30, 0.89)]. For each outcome, the subgroups and the sensitivity analysis matched the overall results. Conclusion: ZBT may be safe and beneficial to HLP patients, especially for serum lipid management. ZBT can be used along with CT for the treatment of HLP. However, it is necessary to conduct more rigorous RCTs to confirm these findings. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022316251].

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