Publications by authors named "Ping Zhou"

1,596 Publications

  • Page 1 of 1

Transcription Factor GATA4 Regulates Cell Type-Specific Splicing Through Direct Interaction With RNA in Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitors.

Circulation 2022 Aug 8:CIRCULATIONAHA121057620. Epub 2022 Aug 8.

Gladstone Institutes, San Francisco, CA (L.Z., K.C., B.G-T., Y-S.A., R.T., N.R.S., L.L., P.Z., Y.H., A.P., F.K., A.P., N.S., A.H., M.W.C., C.A.G., J.v.B., R.H., B.R.C., B.G.B., N.J.K., K.S.P., D.S.).

Background: GATA4 (GATA-binding protein 4), a zinc finger-containing, DNA-binding transcription factor, is essential for normal cardiac development and homeostasis in mice and humans, and mutations in this gene have been reported in human heart defects. Defects in alternative splicing are associated with many heart diseases, yet relatively little is known about how cell type- or cell state-specific alternative splicing is achieved in the heart. Here, we show that GATA4 regulates cell type-specific splicing through direct interaction with RNA and the spliceosome in human induced pluripotent stem cell-derived cardiac progenitors.

Methods: We leveraged a combination of unbiased approaches including affinity purification of GATA4 and mass spectrometry, enhanced cross-linking with immunoprecipitation, electrophoretic mobility shift assays, in vitro splicing assays, and unbiased transcriptomic analysis to uncover GATA4's novel function as a splicing regulator in human induced pluripotent stem cell-derived cardiac progenitors.

Results: We found that GATA4 interacts with many members of the spliceosome complex in human induced pluripotent stem cell-derived cardiac progenitors. Enhanced cross-linking with immunoprecipitation demonstrated that GATA4 also directly binds to a large number of mRNAs through defined RNA motifs in a sequence-specific manner. In vitro splicing assays indicated that GATA4 regulates alternative splicing through direct RNA binding, resulting in functionally distinct protein products. Correspondingly, knockdown of GATA4 in human induced pluripotent stem cell-derived cardiac progenitors resulted in differential alternative splicing of genes involved in cytoskeleton organization and calcium ion import, with functional consequences associated with the protein isoforms.

Conclusions: This study shows that in addition to its well described transcriptional function, GATA4 interacts with members of the spliceosome complex and regulates cell type-specific alternative splicing via sequence-specific interactions with RNA. Several genes that have splicing regulated by GATA4 have functional consequences and many are associated with dilated cardiomyopathy, suggesting a novel role for GATA4 in achieving the necessary cardiac proteome in normal and stress-responsive conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.121.057620DOI Listing
August 2022

Metabolic profile and dynamic characteristic of rhubarb during the vitro biotransformation by human gut microbiota.

Food Chem 2022 Aug 2;397:133840. Epub 2022 Aug 2.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16 Nanxiao Lane, Dongzhimennei, Beijing 100700, China. Electronic address:

Rhubarb is a popular food in the world with laxative effects and steamed pieces of rhubarb (SP) have been widely applied to treatment of constipation in China due to its safety and effectiveness. In the study, metabolism in vitro was conducted to study influence of gut microbiota between raw pieces of rhubarb (RP) and SP. The results showed obvious classifications in metabolic profile between RP and SP were revealed by chemometric analysis, and prompted gut microbiota affected metabolism of rhubarb. Furthermore, 16 characteristic components were identified to distinguish the differences in metabolism. Finally, quantitative analysis of 14 components were verified the regulation of gut microbiota on rhubarb and discovered concentration of components affected the rate of metabolism. The study indicated regulation by gut microbiota could be probably responsible for differences of laxative effects between RP and SP, providing new perspective for exploring mechanisms of effectiveness in clinical application for SP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2022.133840DOI Listing
August 2022

Motor unit distribution and recruitment in spastic and non-spastic bilateral biceps brachii muscles of chronic stroke survivors.

J Neural Eng 2022 Aug 4. Epub 2022 Aug 4.

Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2011, Houston, Houston, 77204, UNITED STATES.

Objective- This study aims to characterize the motor units distribution and recruitment pattern in the spastic and non-spastic bilateral biceps brachii muscles (BBMs) of chronic stroke survivors. Approach- High-density surface electromyography (HD-sEMG) signals were collected from both spastic and non-spastic BBMs of fourteen chronic stroke subjects during isometric elbow flexion at 10%, 30%, 50% and 100% maximal voluntary contractions (MVCs). By combining HD-sEMG decomposition and bioelectrical source imaging, motor unit innervation zones (MUIZs) of the decomposed motor units were first localized in the 3D space of spastic and non-spastic BBMs. The motor unit depth defined as the distance between the localized MUIZ and its normal projection on the skin surface was then normalized to the arm radius of each subject and averaged at given contraction level. The averaged MU depth at different contraction levels on a specific arm side (intra-side) and the bilateral depths under a specific contraction level (inter-side) were compared. Main Results- The average depth of decomposed MUs increased with the contraction force and significant differences observed between 10% vs 50% (p < 0.0001), 10% vs 100% (p < 0.0001) and 30% vs 100% MVC (p = 0.0017) on the non-spastic side, indicating that larger MUs with higher recruitment threshold locate in deeper muscle regions. In contrast, no force-related difference in MU depth was observed on the spastic side, suggesting a disruption of orderly recruitment of MUs with increase of force level, or the MU denervation and the subsequent collateral reinnervation secondary to upper motor neuron lesions. Inter-side comparison demonstrated significant MU depth difference at 10% (p=0.0048) and 100% force effort (p=0.0026). Significance-This study represents the first effort to non-invasively characterize the MU distribution inside spastic and non-spastic bilateral BBM of chronic stroke patients by combining HD-sEMG recording, EMG signal decomposition and bioelectrical source imaging. The findings of this study advances our understanding regarding the neurophysiology of human muscles and the neuromuscular alterations following stroke. It may also offer important MU depth information for botulinum toxin (BoNT) injection in clinical post-stroke spasticity management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1741-2552/ac86f4DOI Listing
August 2022

Generation of an induced pluripotent stem cell line AMUFAHi002-A from polycystic ovary syndrome patient.

Stem Cell Res 2022 Aug 28;63:102875. Epub 2022 Jul 28.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address:

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women of reproductive age. The PCOS leads to obesity, dyslipidemia, insulin resistance, hyperandrogenism, and infertility. We established an induced pluripotent stem cell line (iPSC) from a PCOS patient. This disease-specific iPSC line will be beneficial to study PCOS in vitro, allowing to understand the pathogenic mechanisms and a cell-based model for drug development for PCOS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scr.2022.102875DOI Listing
August 2022

Oral exposure to DEHP may stimulate prostatic hyperplasia associated with upregulation of COX-2 and L-PGDS expressions in male adult rats.

Reprod Toxicol 2022 Jul 26;112:160-170. Epub 2022 Jul 26.

NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School ️of Pharmacy, Fudan University, China. Electronic address:

Di-(2-ethylhexyl) phthalate (DEHP), a typical environmental endocrine disruptor (EED), can disrupt estrogen and androgen secretion and metabolism process, thus inducing dysfunctional reproduction such as impaired gonadal development and spermatogenesis disorder. Prostaglandin synthases (PGS) catalyze various prostaglandins biosynthesis, involved in inflammatory cascade and tumorigenesis. Yet, little is known about how PGS may impact prostatic hyperplasia development and progression. This study concentrates predominantly on the potential prostatic toxicity of DEHP exposure and the mediating role of PGS. In vivo study, adult male rats were administered via oral gavage 30 μg/kg/d, 90 μg/kg/d, 270 μg/kg/d, 810 μg/kg/d DEHP or vehicle for four weeks. The results elucidated that low-dose DEHP may cause the proliferation of the prostate with an increased PCNA/TUNEL ratio. Given the importance of estrogens and androgens in prostatic hyperplasia, our first objective was to evaluate the levels of sex hormones. DEHP improved the ratio of estradiol (E)/testosterone (T) in a dose-dependent manner and upregulated estrogen receptor alpha (ERα) and androgen receptor (AR) expressions. Prostaglandin synthases, including cyclooxygenase-2 (COX-2) and lipocalin-type prostaglandin D synthase (L-PGDS), were significantly upregulated in the ventral prostate. COX-2 and L-PGDS might mediate the tendency of prostatic hyperplasia induced by low-dose DEHP through estradiol/androgen regulation and imbalance between proliferation and apoptosis in vivo. These findings provide the first evidence that prostaglandin synthases contribute to the tendency toward benign prostatic hyperplasia induced by DEHP. Further investigations will have to be performed to facilitate an improved understanding of the role of prostaglandin synthases in DEHP-induced prostatic lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.reprotox.2022.07.008DOI Listing
July 2022

Deep learning based on ultrasound images assists breast lesion diagnosis in China: a multicenter diagnostic study.

Insights Imaging 2022 Jul 28;13(1):124. Epub 2022 Jul 28.

Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China.

Background: Studies on deep learning (DL)-based models in breast ultrasound (US) remain at the early stage due to a lack of large datasets for training and independent test sets for verification. We aimed to develop a DL model for differentiating benign from malignant breast lesions on US using a large multicenter dataset and explore the model's ability to assist the radiologists.

Methods: A total of 14,043 US images from 5012 women were prospectively collected from 32 hospitals. To develop the DL model, the patients from 30 hospitals were randomly divided into a training cohort (n = 4149) and an internal test cohort (n = 466). The remaining 2 hospitals (n = 397) were used as the external test cohorts (ETC). We compared the model with the prospective Breast Imaging Reporting and Data System assessment and five radiologists. We also explored the model's ability to assist the radiologists using two different methods.

Results: The model demonstrated excellent diagnostic performance with the ETC, with a high area under the receiver operating characteristic curve (AUC, 0.913), sensitivity (88.84%), specificity (83.77%), and accuracy (86.40%). In the comparison set, the AUC was similar to that of the expert (p = 0.5629) and one experienced radiologist (p = 0.2112) and significantly higher than that of three inexperienced radiologists (p < 0.01). After model assistance, the accuracies and specificities of the radiologists were substantially improved without loss in sensitivities.

Conclusions: The DL model yielded satisfactory predictions in distinguishing benign from malignant breast lesions. The model showed the potential value in improving the diagnosis of breast lesions by radiologists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13244-022-01259-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334487PMC
July 2022

Comparative Study of Durability Behaviors of Thermoplastic Polypropylene and Thermosetting Epoxy Exposed to Elevated Temperature, Water Immersion and Sustained Bending Loading.

Polymers (Basel) 2022 Jul 21;14(14). Epub 2022 Jul 21.

Key Laboratory of Structures Dynamic Behavior and Control, Ministry of Education, Harbin Institute of Technology, Harbin 150090, China.

The long-term degradation of epoxy as the matrix and adhesive serviced in harsh environments plays a key role in engineering applications. Understanding how to improve the toughness and durability of epoxy through reasonable material replacement and design is significant to prolong the service life of engineering structures. In the present paper, thermoplastic polypropylene and thermosetting epoxy were exposed in a coupling environment of elevated temperature, water immersion and sustained bending loading. The evolutions of mechanical and thermal properties were further analyzed and compared. Long-term life prediction was conducted to evaluate the corrosive resistances of polypropylene and epoxy. It can be found that polypropylene has better hydrophobic behavior compared to epoxy. At 80 °C, the ratios of the diffusion coefficient and saturated water uptake between the two matrices were 114.4 and 2.94. At the longest immersion time of 90 days, the degradation percentages of tensile strength were 4.7% (40 °C), 7.5% (60 °C) and 8.8% (80 °C), respectively, which had the higher strength retention (>90%). The maximum strength increase in the multiples of polypropylene/epoxy and polypropylene/polyurethane was 1.95 and 1.75, respectively. The bending loading led to a maximum increase in tensile strength (~1.47%) owing to the oxygen isolation effect. The degradation mechanism was attributed to the active functional groups from the production process reacting with oxygen, resulting in the fracture of the local chain segment. By comparison, water molecules reacted with the hydroxyl groups or interrupted the intermolecular Van der Waals force/hydrogen bond of the epoxy, resulting in irreversible hydrolysis and property degradation. Through the comparison, it can be found that polypropylene and its composites have outstanding properties compared to epoxy, which can make them achieve great application prospects in engineering applications when considering a complex service environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym14142953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325122PMC
July 2022

Blood-brain barrier penetrating carbon dots with intrinsic anti-inflammatory and drug-loading properties.

Biomater Adv 2022 Aug 22;139:212995. Epub 2022 Jun 22.

College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China; Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing 400016, PR China; Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, Chongqing 400016, PR China. Electronic address:

The blood-brain barrier (BBB) is the major obstacle limiting the reach of therapeutic drugs into the brain. Herein, an aspirin-based anti-inflammatory replenisher (aspCD) was fabricated by carbonizing aspirin to deliver drugs into the brain visually. The as-prepared aspCD combined the BBB-penetrating and anti-inflammatory effects of aspirin with the fluorescent and drug-loading properties of carbon dots (CDs), thereby delivering therapeutic drugs into the brain and acting as imaging agent as well as anti-inflammatory replenisher. In vivo experiments of mice and zebrafish revealed that fluorescence aspCD could effectively penetrate BBB. In vitro and in vivo inflammatory models demonstrated that aspCD could be regarded as an excellent anti-inflammatory replenisher. In addition, as a functional carrier, aspCD was proved to be capable of loading drugs with different polarity. In summary, carbonization of active precursors (therapeutic drugs) into CDs could be a promising strategy to achieve the loading and visualization of drugs as well as the retainment of their biological activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioadv.2022.212995DOI Listing
August 2022

Targeting Undruggable Transcription Factors with PROTACs: Advances and Perspectives.

J Med Chem 2022 Jul 26. Epub 2022 Jul 26.

Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.

Dysregulation of transcription factors has been implicated in a variety of human diseases. However, these proteins have traditionally been regarded as undruggable and only a handful of them have been successfully targeted by conventional small molecules. Moreover, the development of intrinsic and acquired resistance has hampered the clinical use of these agents. Over the past years, proteolysis-targeting chimeras (PROTACs) have shown great promise because of their potential for overcoming drug resistance and their ability to target previously undruggable proteins. Indeed, several small molecule-based PROTACs have demonstrated superior efficacy in therapy-resistant metastatic cancers. Nevertheless, it remains challenging to identify ligands for the majority of transcription factors. Given that transcription factors recognize short DNA motifs in a sequence-specific manner, multiple novel approaches exploit DNA motifs as warheads in PROTAC design for the degradation of aberrant transcription factors. These PROTACs pave the way for targeting undruggable transcription factors with potential therapeutic benefits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.2c00691DOI Listing
July 2022

Surface-Sensitive Imaging Analysis of Cell-Microenvironment Interactions by Electrochemiluminescence Microscopy.

Anal Chem 2022 Aug 24;94(30):10885-10892. Epub 2022 Jul 24.

Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou 310000, China.

A complex and heterogeneous cell microenvironment offers not only structural support for cells but also myriad biochemical and biophysical cues. These outside-in signals transmit into cells primarily through integrins, which are the important components of cell-matrix adhesions to direct and maintain cell behaviors and fate. In this work, we report a surface-sensitive imaging methodology for evaluating the difference in cell-matrix adhesions at the single cell level to dissect the impact of the chemical microenvironment on cell behaviors. Cells were cultured on silica nanochannel membrane (SNM) modified indium tin oxide (ITO) electrodes (SNM/ITO) with different terminal surfaces and imaged by electrochemiluminescence microscopy (ECLM). The results show that the surface tethered with Arg-Gly-Asp (RGD) groups can mediate robust cell-microenvironment interaction and those coated with silanol and (3-aminopropyl)triethoxysilane (APTES) groups transmit an intermediate adhesion, while oligo(ethylene glycol) (OEG) coated surface conveys the weakest cell-matrix adhesion. Specific recognition of integrins to different surfaces was further explored in conjunction with selective immunoblocking of different subunits. α6, α5, and α1 integrin subunits were found to recognize SNM, RGD/OEG, and APTES surfaces, respectively. The work provides not only insights into cell-microenvironment interaction but also guideline in the design and development of functional and biomimetic surface materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.2c02479DOI Listing
August 2022

Causes of Death in Long-Term Nasopharyngeal Carcinoma Survivors.

Front Public Health 2022 7;10:912843. Epub 2022 Jul 7.

Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Purpose: To assess the causes of death (COD) and long-term survival after nasopharyngeal carcinoma (NPC) diagnosis.

Methods: Using linked data from the Surveillance, Epidemiology, and End Results program, patients with NPC diagnosed from 1990 to 2010 and followed up >5 years were identified. Chi-squared test, the Kaplan-Meier method, and the Cox proportional hazard model were used for analyses.

Results: Among the 3,036 long-term NPC survivors, 1,432 survived for >5-10 years and 1,604 survived for >10 years. The most common COD was primary NPC (36.9%), followed by other causes (28.7%), other cancers (15.3%), cardiac disease (12.9%), and non-malignant pulmonary disease (6.2%). With a median follow-up of 125 months, deaths from NPC decreased with increasing time from diagnosis, while death because of cardiac disease and other causes increased. In those aged <50 years, death due to NPC remained the main COD over time, while cardiopulmonary disease-related death was the leading COD in patients aged ≥50 years. In White patients, death due to NPC decreased, and death due to cardiac disease increased over time. Death from NPC remained significant in Black and Asian patients even 15 years after the diagnosis of NPC, while death due to cardiac disease significantly increased after 9 years of diagnosis in Black patients. Multivariate analyses showed that the independent factors associated with inferior NPC-specific survival were older age, Asians, American Indian/Alaska Native, regional stage, distant stage, and diagnosis in the early years.

Conclusions: The probability of death from primary NPC remains significant even 15 years after the NPC diagnosis. Our study advocates continued surveillance for NPC survivors beyond the traditional 5 years. Individualized follow-up strategies are required for patients with NPC of different ages and races.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2022.912843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301133PMC
July 2022

Rapid Detection of in Clinical Samples From Different Sources Using RPA-LFS.

Front Cell Infect Microbiol 2022 7;12:898186. Epub 2022 Jul 7.

Department of Central Laboratory, Lianyungang Hospital Affiliated to Jiangsu University (Cancer Hospital of Lianyungang), Lianyungang, China.

is one of the few Candida species besides that is able to produce true hyphae. At present, the commonly used clinical methods for the identification of this organism are traditional fungal culture, CTB staining, and color development. Polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR) are also used to identify this fungus. Since the course of . infection progresses rapidly, there is an urgent need for rapid, sensitive, real-time field assays to meet the needs of clinical diagnosis. Recombinase polymerase amplification (RPA) combined with lateral flow strip (LFS) can rapidly amplify and visualize target genes within 20 min, and by pre-processing samples from different sources, the entire process can be controlled within 30 min. In this study, RPA-LFS was used to amplify the internal transcribed spacer-2 () gene of . , and primer-probe design was optimized by introducing base mismatches to obtain a specific and sensitive primer-probe combination for clinical sample detection. LFS assay for 37 common clinical pathogens was performed, sensitivity and specificity of the detection system was determined, reaction temperature and time were optimized, and 191 actual clinical samples collected from different sources were tested to evaluate the detection performance of the established RPA-LFS system to provide a reliable molecular diagnostic method for the detection of . , the results show that the RPA-LFS system can specifically detect without cross-reacting with other fungi or bacterial, with a sensitivity of 9.94 CFU/µL, without interference from genomic DNA of other species, at an optimal reaction temperature of 39°C, and the whole reaction process can be controlled within 20 min, and to meet the clinical need for rapid, sensitive, real-time, and portable field testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2022.898186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301490PMC
July 2022

Gain-of-function mutations in cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.

Ann Rheum Dis 2022 Jul 22. Epub 2022 Jul 22.

Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.

Objectives: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in , is an autoinflammatory disease.

Methods: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of mutations on protein function and immune signalling.

Results: The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys.Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients).Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the T237M mutation exhibited subclinical inflammation.Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow.

Conclusion: ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in and some features of disease are amenable to immunomodulatory therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2022-222629DOI Listing
July 2022

Earlier or heavier spinal loading is more likely to lead to recurrent lumbar disc herniation after percutaneous endoscopic lumbar discectomy.

J Orthop Surg Res 2022 Jul 16;17(1):356. Epub 2022 Jul 16.

Department of Orthopedic Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China.

Purpose: To evaluate the clinical features of and risk factors for recurrent lumbar disc herniation (rLDH) after percutaneous endoscopic lumbar discectomy (PELD) in our clinical practice.

Methods: A total of 942 consecutive patients who underwent single-level PELD from January 2013 to August 2019 were included. Patients were divided into the recurrence group and the nonrecurrence group. Patient characteristics, radiographic parameters and surgical variables were compared between the two groups. Univariate analysis and multiple logistic regression analysis were adopted to determine the risk factors for recurrence after PELD.

Results: The prevalence of rLDH was 6.05%. Age, sex, tobacco use, duration of low back pain, body mass index (BMI), occupational lifting, herniated disc type, facet joint degeneration, operation time and time to ambulation were significantly different between the two groups. Univariate analysis showed that age (P < 0.001), sex (P = 0.019), BMI (P = 0.001), current smoking (P < 0.001), occupational lifting (P < 0.001), facet joint degeneration (P = 0.001), operation time (P = 0.002), and time to ambulation (P < 0.001) could be significantly associated with the incidence of rLDH after PELD. Multivariate analysis suggested that an older age (P < 0.001), the male sex (P = 0.017), a high BMI (P < 0.001), heavy work (P = 0.003), grade II facet joint degeneration (P < 0.001) and early ambulation (P < 0.001) were significantly related to rLDH after PELD.

Conclusions: An older age, the male sex, a higher BMI, heavy work, grade II facet joint degeneration, and early ambulation are independent significant risk factors for rLDH after PELD. Great importance should be attached to these risk factors to prevent rLDH. We suggest that patients control their weight, avoid heavy work, ambulate at an appropriate time, and perform strengthening rehabilitation exercises to reduce the incidence of rLDH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13018-022-03242-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288683PMC
July 2022

UC-MSCs promote frozen-thawed ovaries angiogenesis via activation of the Wnt/β-catenin pathway in vitro ovarian culture system.

Stem Cell Res Ther 2022 07 15;13(1):296. Epub 2022 Jul 15.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.

Background: Ovarian tissue cryopreservation and transplantation are novel therapeutic approaches for fertility preservation. However, follicle loss caused by ischemic and hypoxic damage is one of the issues after frozen-thawed ovarian tissue transplantation. Promoting angiogenesis in grafts is the key to restore cryopreserved ovarian function. Mesenchymal stem cells (MSCs) have been reported to facilitate angiogenesis in the cryopreserved ovarian tissue transplantation. However, the risk of embolization, immunogenic effect and tumorigenesis hinders the clinical application of MSCs to human organ transplantation. In this study, we established an in vitro ovarian culture system to restore frozen-thawed ovarian function before transplantation with the application of umbilical cord mesenchymal stem cells (UC-MSCs), and explored the effects of UC-MSCs on frozen-thawed ovaries in vitro ovarian culture system and the mechanisms of UC-MSCs on the angiogenesis of frozen-thawed ovaries.

Methods: A simple in vitro three dimensional (3D) ovarian culture system using Matrigel was established to support to an ideal niche, and ovary was alone cultured in the 24-well plate as a control. We also evaluated the effects of UC-MSCs treatment on ovarian function with or without Matrigel support. All thawed ovaries were randomly divided into control group (Matrigel-/UC-MSCs-), Matrigel group (Matrigel+/UC-MSCs-), UC-MSCs group (Matrigel-/UC-MSCs+) and UC-MSCs + Matrigel group (Matrigel+/UC-MSCs+). HE staining was used to detect the histological structure of follicles and TUNEL staining was used to detect cell apoptosis. The number of microvessels was counted to evaluate neovascularization. The mRNA expression of VEGFA, IGF1 and ANGPT2 were detected by RT-PCR. Western blotting was used to measure the expression of GSK-3β, β-catenin and p-β-catenin.

Results: In the absence of UC-MSCs, 3D culture system supported by Matrigel showed significantly improved follicular development and microvascular number. Additionally, UC-MSCs were also found to effectively improve follicular development and microvascular number regardless of the culture condition used. However, alleviated follicular apoptosis, increased mRNA expression of angiogenesis-related gene and activated Wnt/β-catenin pathway occurred only in the UC-MSCs + Matrigel group. Besides, with the application of IWP-2 in UC-MSCs + Matrigel group, Wnt//β-catenin pathway could be blocked by IWP-2 serving as one of Wnt/β-catenin pathway inhibitors.

Conclusions: This in vitro study showed the beneficial effects of UC-MSCs on thawed ovaries and explored a potential mechanism inducing angiogenesis. In particular, 3D ovarian culture system supported by Matrigel further improved UC-MSCs treatment. The in vitro culture system using Matrigel and UC-MSCs may provide a potential treatment strategy for improving the success rate of thawed ovaries transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-022-02989-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284710PMC
July 2022

Integrative Analyses of m6A Regulators Identify that METTL3 is Associated with HPV Status and Immunosuppressive Microenvironment in HPV-related Cancers.

Int J Biol Sci 2022 3;18(9):3874-3887. Epub 2022 Jun 3.

Department of Gynecology and Obstetrics, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Although m6A modifications are associated with tumor progression, and anti-tumor immune responses, the role of m6A regulators in HPV-related carcinogenesis has not been well resolved. To provide evidence for the role of m6A regulators in HPV-related carcinogenesis and identify potential therapeutic targets for HPV-related cancers, integrative analyses of m6A regulators in 1,485 head and neck squamous cell carcinoma (HNSC) patients and 507 cervical squamous cell carcinoma (CESC) patients was performed and identified that an m6A regulator, METTL3, was highly expressed in tumors and was related to the poor prognosis in HNSC and CESC. In HPV-positive tumors, METTL3 was positively associated with tumor HPV status, such as HPV integration status, E6 and unspliced-E6 expression, and p16 expression. Further analysis demonstrated that METTL3 status was negatively correlated with tumor immune cell infiltrations and facilitated the expression of immunosuppressive immune checkpoint molecules (i.e., PD-L1). Cell-derived xenograft models demonstrated that METTL3 inhibitor combined with anti-PD1 therapy promoted immunotherapy of CESC . Overall, this study identified that METTL3 status, is associated with poor prognosis and HPV status, and serves as a mediator of the immunosuppressive tumor microenvironment in HPV-associated cancer, which provides a promising therapeutic target for anti-cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.70674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254478PMC
July 2022

HDACs regulate the differentiation of endothelial cells from human iPSCs.

Cell Biochem Funct 2022 Jul 5. Epub 2022 Jul 5.

Stem Cell Program, University of California Davis Medical Center, Sacramento, California, USA.

Human induced pluripotent stem cells (hiPSCs) possess the potential to differentiate toward vascular cells including endothelial cells (ECs), pericytes, and smooth muscle cells. Epigenetic mechanisms including DNA methylation and histone modification play a crucial role in regulating lineage differentiation and specification. Herein, we utilized a three-stage protocol to induce differentiation of mesoderm, vascular progenitors, and ECs from hiPSCs and investigated the regulatory effects of histone acetylation on the differentiation processes. We found that the expression of several histone deacetylases (HDACs), including HDAC1, HDAC5, and HDAC7, were greatly upregulated at the second stage and downregulated at the third stage. Interestingly, although HDAC1 remained in the nucleus during the EC differentiation, HDAC5 and HDAC7 displayed cytosol/nuclear translocation during the differentiation process. Inhibition of HDACs with sodium butyrate (NaBt) or BML210 could hinder the differentiation of vascular progenitors at the second stage and facilitate EC induction at the third stage. Further investigation revealed that HDAC may modulate the stepwise EC differentiation via regulating the expression of endothelial transcription factors ERG, ETS1, and MEF2C. Opposite to the expression of EC markers, the smooth muscle/pericyte marker ACTA2 was upregulated at the second stage and downregulated at the third stage by NaBt. The stage-specific regulation of ACTA2 by HDAC inhibition was likely through regulating the expression of TGFβ2 and PDGFB. This study suggests that HDACs play different roles at different stages of EC induction by promoting the commitment of vascular progenitors and impeding the later stage differentiation of ECs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbf.3729DOI Listing
July 2022

Porcine Fibrin Sealant Promotes Skin Wound Healing in Rats.

Evid Based Complement Alternat Med 2022 23;2022:5063625. Epub 2022 Jun 23.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.

Objective: Fibrin sealant (FS) is widely used for skin wound healing, but data on porcine FS (PFS), a new type of FS, are limited. This study investigated the effects and potential mechanisms of porcine fibrin sealant (PFS) on skin wound healing in rats. Traumatic rats were randomly divided into three groups: control, PFS, and medical Vaseline. The wound area and wound index of the rats were measured within 14 days after surgery. Hematoxylin-eosin (H&E) staining and Masson staining were used to observe the pathological images and collagen formation on the wounded skin, respectively. To investigate the healing mechanisms, the enzyme-linked immunosorbent assay (ELISA) was used to detect platelet endothelial cell adhesion molecule-1 (CD31) and cluster of differentiation 34 (CD34) expression in the wounded skin. Additionally, quantitative real-time PCR (qRT-PCR) was used to evaluate the mRNA levels of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF), and transforming growth factor-1 (TGF-1). Meanwhile, TGF-1 protein expression was assessed by Western blot analysis.

Results: Compared with the control group, both PFS and medical Vaseline treatment significantly reduced the wounded area and increased the wound closure rate. H&E staining showed that the cells in the PFS group proliferated rapidly, and the epidermis and dermis were thickened to some extent with a clear epidermal cell structure. Moreover, PFS promoted the formation of collagen and significantly increased the levels of CD31 and CD34 and the growth factors in the skin tissues of the traumatic rats.

Conclusion: PFS effectively promoted skin wound healing, especially in tissue formation, reepithelialization, angiogenesis, and collagen deposition, in traumatic rat models. This study provides a new strategy and scientific foundation for PFS application in skin wound healing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/5063625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246592PMC
June 2022

Lysosomal dysfunction is associated with NLRP3 inflammasome activation in chronic unpredictable mild stress-induced depressive mice.

Behav Brain Res 2022 08 1;432:113987. Epub 2022 Jul 1.

Department of Medical Psychology, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, China. Electronic address:

NLRP3 inflammasome pathway-mediated inflammatory response is closely associated with depression. Increasing attention has been recently paid to the links between autophagy and depression, however, the relationship between autophagy and NLRP3 inflammasome in depressive behavior remain poorly understood. In the present study, the potential roles of autophagy-lysosome pathway in NLRP3 inflammasome regulation were investigated both in vivo (chronic unpredictable mild stress (CUMS)-induced depressive mouse model) and in vitro (LPS-induced cellular model) model. It demonstrated that CUMS induces depressive-like behaviors in mice, accompanied by increased expression of NLRP3 inflammasome and inflammatory responses. Meanwhile, it promoted the autophagosome marker LC3 and autophagic adapter protein p62 accumulation, accompanied by the decrease of lysosomal cathepsins B and D expression in the prefrontal cortex of mice. Notably, a significant colocalization of NLRP3 and LC3 in CUMS mice by immunofluorescence co-staining were observed. For the in vitro study, disrupting the lysosomal function with Baf A1 significantly increased the LPS-induced NLRP3 inflammasome accumulation and pro-inflammatory factors (IL-1β and IL-18) production in BV2 cells. Collectively, our results suggested that the autophagic process is related to NLRP3 inflammasome activation, and dysfunctional lysosome in autophagy-lysosomal pathway may retard NLRP3 inflammasome degradation, facilitating the production of pro-inflammatory factors, thereby contributing to depressive behavior in CUMS mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2022.113987DOI Listing
August 2022

An Analysis of the Effect of Abrasive/Tool Wear on the Ductile Machining of Fused Silica from the Perspective of Stress.

Micromachines (Basel) 2022 May 25;13(6). Epub 2022 May 25.

Key Laboratory for Precision and Non-Traditional Machining Technology of Ministry of Education, School of Mechanical Engineering, Dalian University of Technology, Dalian 116024, China.

Understanding the influence mechanism of abrasive/tool wear on machining is the key to realize high-efficiency ultra-precision machining of fused silica. To explore the effect of abrasive/tool wear on ductile machining, the smoothed particle hydrodynamics (SPH) cutting models with different edge radii are established. Through the analysis of equivalent rake angle, hydrostatic pressure, cutting force and maximum principal stress with the Flamant's formula, the influence of edge radii on ductile-brittle transition (DBT) is discussed for the first time. The simulation results show that when the edge radius increases from less to larger than the cutting depth, the equivalent rake angle changes from positive to negative, and the maximum hydrostatic pressure gradually increases, which is beneficial to promote the ductile processing. Meanwhile, with the rise of edge radius (i.e., abrasive/tool wear), both the cutting force and crack initiation angle increase, while the friction coefficient and normalized maximum principal decrease. When the value of normalized maximum principal stress exceeds 2.702, the crack in the workpiece begins to initiate, and its initiation angle calculated by the Flamant's formula is in good agreement with the simulation results as well as less than 50°. Finally, the nano-scratch experiment was carried out, and the material removal mechanism and friction coefficient similar to the simulation were obtained, which further proved the accuracy of SPH model. This study is meaningful for understanding the effect of abrasive/tool wear on the removal mechanism of brittle materials and improving the quality and efficiency of cutting and grinding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/mi13060820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227195PMC
May 2022

Neural network interpolation operators optimized by Lagrange polynomial.

Neural Netw 2022 Sep 10;153:179-191. Epub 2022 Jun 10.

Department of Mathematics and Statistics, St. Francis Xavier University, Antigonish, NS B2G 2W5, Canada. Electronic address:

In this paper, we introduce a new type of interpolation operators by using Lagrange polynomials of degree r, which can be regarded as feedforward neural networks with four layers. The approximation rate of the new operators can be estimated by the (r+1)-th modulus of smoothness of the objective functions. By adding some smooth assumptions on the activation function, we establish two important inequalities of the derivatives of the operators. With these two inequalities, by using the K-functional and Berens-Lorentz lemma in approximation theory, we establish the converse theorem of approximation. We also give the Voronovskaja-type asymptotic estimation of the operators for smooth functions. Furthermore, we extend our operators to the multivariate case, and investigate their approximation properties for multivariate functions. Finally, some numerical examples are given to demonstrate the validity of the theoretical results obtained and the superiority of the operators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neunet.2022.06.007DOI Listing
September 2022

Pulmonary granulomatous inflammation after ceritinib treatment in advanced ALK-rearranged pulmonary adenocarcinoma.

Invest New Drugs 2022 Jun 21. Epub 2022 Jun 21.

Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan, Chengdu, China.

Ceritinib is a new anaplastic lymphoma kinase (ALK) inhibitor that has shown greater potency in patients with advanced ALK-rearranged non-small cell lung cancer, including those who had disease progression in crizotinib treatment. Here we reported, after several months of ceritinib treatment, two patients with advanced ALK-rearranged pulmonary adenocarcinoma exhibited a spectrum of respiratory symptoms like cough and dyspnea, with significantly higher inflammatory indicators. Chest computed tomography (CT) showed multiple bilateral and peripheral lesions in lungs. The prior considerations taken into account were disease progression or infection. However, biopsies of the pulmonary nodules revealed features of granulomatous inflammation without definite cancer cells. We documented for the first time that ceritinib might be associated with pulmonary granulomatous inflammation, and clinicians should be alert to the possibility that the rare adverse event emerged during ceritinib treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-022-01270-2DOI Listing
June 2022

Caution Is Necessary for Acceptance of Motor Units With Intermediate Matching in Surface EMG Decomposition.

Front Neurosci 2022 26;16:876659. Epub 2022 May 26.

Biomedical and Rehabilitation Engineering Program, University of Health and Rehabilitation Sciences, Qingdao, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2022.876659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199354PMC
May 2022

A database of animal metagenomes.

Sci Data 2022 06 16;9(1):312. Epub 2022 Jun 16.

State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, Xinjiang, China.

With the rapid development of high-throughput sequencing technology, the amount of metagenomic data (including both 16S and whole-genome sequencing data) in public repositories is increasing exponentially. However, owing to the large and decentralized nature of the data, it is still difficult for users to mine, compare, and analyze the data. The animal metagenome database (AnimalMetagenome DB) integrates metagenomic sequencing data with host information, making it easier for users to find data of interest. The AnimalMetagenome DB is designed to contain all public metagenomic data from animals, and the data are divided into domestic and wild animal categories. Users can browse, search, and download animal metagenomic data of interest based on different attributes of the metadata such as animal species, sample site, study purpose, and DNA extraction method. The AnimalMetagenome DB version 1.0 includes metadata for 82,097 metagenomes from 4 domestic animals (pigs, bovines, horses, and sheep) and 540 wild animals. These metagenomes cover 15 years of experiments, 73 countries, 1,044 studies, 63,214 amplicon sequencing data, and 10,672 whole genome sequencing data. All data in the database are hosted and available in figshare https://doi.org/10.6084/m9.figshare.19728619 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41597-022-01444-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203544PMC
June 2022

Can Artificial Intelligence Be Applied to Diagnose Intracerebral Hemorrhage under the Background of the Fourth Industrial Revolution? A Novel Systemic Review and Meta-Analysis.

Int J Clin Pract 2022 24;2022:9430097. Epub 2022 Feb 24.

Department of Neurosurgery, Qinghai Provincial People's Hospital, Xining 810007, Qinghai, China.

Aim: We intended to provide the clinical evidence that artificial intelligence (AI) could be used to assist doctors in the diagnosis of intracerebral hemorrhage (ICH).

Methods: Studies published in 2021 were identified after the literature search of PubMed, Embase, and Cochrane. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to perform the quality assessment of studies. Data extraction of diagnosis effect included accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), area under curve (AUC), and Dice scores (Dices). The pooled effect with its 95% confidence interval (95%CI) was calculated by the random effects model. -Square ( ) was used to test heterogeneity. To check the stability of the overall results, sensitivity analysis was conducted by recalculating the pooled effect of the remaining studies after omitting the study with the highest quality or the random effects model was switched to the fixed effects model. Funnel plot was used to evaluate publication bias. To reduce heterogeneity, recalculating the pooled effect of the remaining studies after omitting the study with the lowest quality or perform subgroup analysis.

Results: Twenty-five diagnostic tests of ICH via AI and doctors with overall high quality were included. Pooled ACC, SEN, SPE, PPV, NPV, AUC, and Dices were 0.88 (0.83∼0.93), 0.85 (0.81∼0.89), 0.90 (0.88∼0.92), 0.80 (0.75∼0.85), 0.93 (0.91∼0.95), 0.84 (0.80∼0.89), and 0.90 (0.85∼0.95), respectively. There was no publication bias. All of results were stable as revealed by sensitivity analysis and were accordant as outcomes via subgroups analysis.

Conclusion: Under the background of the fourth industrial revolution, AI might be an effective and efficient tool to assist doctors in the clinical diagnosis of ICH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/9430097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159188PMC
June 2022

Effects of the Pre-Consolidated Materials Manufacturing Method on the Mechanical Properties of Pultruded Thermoplastic Composites.

Polymers (Basel) 2022 May 31;14(11). Epub 2022 May 31.

Center for Materials Technologies, Skolkovo Institute of Science and Technology, 30/1 Bolshoi Boulevard, 121205 Moscow, Russia.

The choice of a manufacturing process, raw materials, and process parameters affects the quality of produced pre-consolidated tapes used in thermoplastic pultrusion. In this study, we used two types of pre-consolidated GF/PP tapes-commercially available (ApATeCh-Tape Company, Moscow, Russia) and inhouse-made tapes produced from commingled yarns (Jushi Holdings Inc., Boca Raton, FL, USA)-to produce pultruded thermoplastic Ø 6 mm bars and 75 mm × 3.5 mm flat laminates. Flat laminates produced from inhouse-made pre-consolidated tapes demonstrated higher flexural, tensile, and apparent interlaminar shear strength compared to laminates produced from commercial pre-consolidated tapes by as much as 106%, 6.4%, and 27.6%, respectively. Differences in pre-consolidated tape manufacturing methods determine the differences in glass fiber impregnation and, thus, differences in the mechanical properties of corresponding pultruded composites. The use of commingled yarns (consisting of matrix and glass fibers properly intermingled over the whole length of prepreg material) makes it possible to achieve a more uniform impregnation of inhouse-made pre-consolidated tapes and to prevent formation of un-impregnated regions and matrix cracks within the center portion of the fiber bundles, which were observed in the case of commercial pre-consolidated tapes. The proposed method of producing pre-consolidated tapes made it possible to obtain pultruded composite laminates with larger cross sections than their counterparts described in the literature, featuring better mechanical properties compared to those produced from commercial pre-consolidated tapes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym14112246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182644PMC
May 2022

Ginsenoside Rb1 inhibits oxidative stress-induced ovarian granulosa cell injury through Akt-FoxO1 interaction.

Sci China Life Sci 2022 Jun 1. Epub 2022 Jun 1.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.

Ginsenoside Rb1 shows a strong antioxidant effect and has potential activation effects on Akt. The aim of the present study was to investigate the protective effect of Rb1 on age-related ovarian granulosa cell injury. Ovarian granulosa cells (GCs) were obtained from 50 young women (≤30 years) and 50 aged women (≥38 years) at an IVF center. Young and aged ICR mice were administered with or without Rb1 (10 mg kg, i.p.) for 2 weeks. The protective effects of Rb1 were investigated and the role of Rb1 on the modulation of Akt-FoxO1 interaction was determined with immunofluorescence, Western blotting, immunoprecipitation, siRNA silencing and pharmacological inhibitor. Rb1 effectively decreased LDH and MDA, and reversed the apoptotic-related protein levels in hGL cells from old patients. Similar results were found in mice. In addition, the mitochondrial membrane potential was restored and the overaccumulation of ROS was reversed by Rb1. Rb1 preserved peroxide-impaired Akt activation, to some extent, by increasing phosphorylation at Ser473. Rb1 also facilitated p-Akt binding to FoxO1 and promoted the phosphorylation of FoxO1. SiRNA silencing of Akt, Akt inhibitor LY294002, and FoxO1 inhibitor AS1842856 attenuated the effects of Rb1. Ginsenoside Rb1 inhibits age-related GCs oxidative damage by activating Akt phosphorylation at Ser473 and by further interaction with FoxO1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-021-2080-xDOI Listing
June 2022

ZIF-based carbon dots with lysosome-Golgi transport property as visualization platform for deep tumour therapy hierarchical size/charge dual-transform and transcytosis.

Nanoscale 2022 Jun 16;14(23):8510-8524. Epub 2022 Jun 16.

College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

The poor penetration of nanomaterials in solid tumours and difficulty in monitoring their penetration depth are major obstacles in their application for the treatment of solid tumours. Herein, pH-responsive carbon dots (ZCD) based on a zeolitic imidazolate framework (ZIF-8) were fabricated to achieve the deep delivery of the chemotherapeutic doxorubicin (DOX) a hierarchical size/charge dual-transformation and transcytosis. The as-prepared ZCD accumulated in the solid tumour and the acidic tumour microenvironment further triggered its decomposition. Firstly, ZCD was decomposed by the weakly acidic extracellular microenvironment of the solid tumour, enabling it to transform into small and neutrally charged particles. Subsequently, these particles were endocytosed by lysosomes, and further disintegrated into smaller and positively charged particles, which could target the Golgi apparatus. Consequently, ZCD delivered DOX deep into the solid tumour a size-shrinking strategy and Golgi-mediated transcytosis, thus significantly improving its antitumour efficacy. In addition, carbonization endowed ZCD with superior fluorescence property, which was enhanced in the acidic microenvironment, thus improving the sensitivity and accuracy of monitoring of the penetration depth of the nanomedicine in real time. Collectively, our results confirmed that the carbon dots obtained the direct carbonization of ZIF-8 simultaneously exhibited enhanced deep penetration into solid tumours and fluorescence, which could be monitored, and that the carbonization of functional materials is effective to enhance their fluorescence, and further broaden their applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2nr02134jDOI Listing
June 2022

Development and Clinical Application of a Recombinase Polymerase Amplification-Lateral Flow Strip Assay for Detection of Carbapenem-Resistant .

Front Cell Infect Microbiol 2022 11;12:876552. Epub 2022 May 11.

Department of Central Laboratory, Department of Laboratory Medicine, the Second People's Hospital of Lianyungang City (Cancer Hospital of Lianyungang), Lianyungang, China.

is a worldwide, primary cause of respiratory tract infections, septicemia, urinary apparatus infections, and secondary meningitis. It can be fatal. Rapid and accurate detection methods are needed to control the spread of carbapenem-resistant (CRAB). Current molecular diagnostic methods are limited and not suitable for on-site detection. In this study, an isothermal detection method using recombinase polymerase amplification (RPA) combined with a lateral flow strip (LFS) was developed to target the and genes of . . The reaction was completed in about 40 min at 37°C. This method can also effectively distinguish and CRAB. The limit of detection of 10-10 CFU/reaction was equal to that of other detection methods. The detection accuracy was equal to that of the qPCR method with the use of clinical samples. The RPA-LFS assay is portable, rapid, and accurate and could replace existing detection methods for on-site detection of . and CRAB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2022.876552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131934PMC
May 2022

Proteins Involved in Synaptic Plasticity Are Downregulated in the Cerebrospinal Fluid of Infants With Clinical Sepsis Complicated by Neuroinflammation.

Front Cell Neurosci 2022 11;16:887212. Epub 2022 May 11.

Department of Neonatology, Bao'an Women and Children's Hospital, Jinan University, Shenzhen, China.

Newborn infants are prone to sepsis and related inflammation of different organs. Neuroinflammation has been associated with long-term adverse neuronal (neuropsychiatric/neurodegenerative) outcomes, including attention deficit hyperactivity disorder (ADHD) or even Alzheimer's disease. Despite a vast number of findings on sepsis-induced inflammatory responses in the central nervous system (CNS), how neuroinflammation affects brain development remains largely elusive. In this study, neonates with clinical sepsis and screened for meningitis were included and classified by the neuroinflammation status based on cerebrospinal fluid (CSF) parameters (INF vs. NOINF). CSF samples collected from clinical screening were subjected to proteomics analysis. Proteins with differential abundance were subjected to enrichment analysis to reveal affected biological pathways. INF and NOINF infants had similar demographic data and hematological and biochemical parameters in blood and CSF. The CSF proteomes were essentially different between the two groups. All 65 proteins with differential abundance showed lower abundance in the INF group and functionally covered pivotal developmental processes, including axonal and synaptic function and extracellular homeostasis. CSF proteins, PTPRZ1 and IGFBP4, were correlated with C-reactive protein (CRP) and ratios of immature/total neutrophils in blood. In general, a substantial change in the CSF protein profile was found under neuroinflammation, and these changes are related to systemic conditions. The results suggest that changes in CSF proteins may be involved in sepsis-affected neurodevelopment, such as disturbances in circuit formation, which has the potential to predispose neonates to long-term adverse outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2022.887212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130476PMC
May 2022
-->