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1.
J Nat Prod ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503996

RESUMO

Eleven new pyranochromones, calomembranone A-K (1-11), two new pyranocoumarins, calopolyanolide E and F (12 and 13), together with six known analogues (14-19) were isolated from the leaves of Calophyllum membranaceum. Their structures and absolute configurations were elucidated by analysis of spectroscopic data, computational calculations, as well as X-ray crystallography of 4 and 9. The anti-inflammatory activities of all the isolates were evaluated by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Structure-activity relationships are also discussed. Compound 7 showed the strongest NO inhibition (IC50 = 0.92 µM). Oral administration of 7 dose-dependently reduced the paw swelling and downregulated neutrophil-to-lymphocyte ratio in the carrageenan-induced acute arthritis mice model. Molecular dynamics simulation and cellular thermal shift assay results indicated that 7 participated in a robust and stable interaction with the active site of TLR4. Compound 7 also suppressed the inflammation in arthritis through the regulation of TLR4 mediated signal transduction via IKK/NF-κB signaling pathway and the consequent reduction of IL-2, IL-4, and IL-5.

2.
Microbiol Spectr ; : e0005922, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543560

RESUMO

Candida tropicalis, a nonmodel diploid microbe, has been applied in industry as a chassis cell. Metabolic engineering of C. tropicalis is challenging due to a lack of gene editing and regulation tools. Here, we report a tRNA:guide RNA (gRNA) platform for boosting gene editing and silencing efficiency in C. tropicalis. As the endogenous tRNA-processing system enables autocleavage for producing a large number of mature gRNAs, a tRNAGly sequence from the genome of C. tropicalis ATCC 20336 was selected for constructing the tRNA:gRNA platform. In the CRISPR-Cas9 system, the tRNA:gRNA platform proved to be efficient in single-gene and multi-gene editing. Furthermore, based on the tRNA:gRNA platform, a CRISPR interference (CRISPRi) system was developed to construct an efficient dCas9-mediated gene expression regulation system for C. tropicalis. The CRISPRi system was employed to regulate the expression of the exogenous gene GFP3 (green fluorescent protein) and the endogenous gene ADE2 (phosphoribosylaminoimidazole carboxylase). Different regions of GFP3 and ADE2 were targeted with the gRNAs processed by the tRNAGly, and the transcription levels of GFP3 and ADE2 were successfully downregulated to 23.9% ± 4.1% and 38.0% ± 7.4%, respectively. The effects of the target regions on gene regulation were also investigated. Additionally, the regulation system was applied to silence ERG9 (squalene synthase) to enhance ß-carotene biosynthesis in a metabolically modified C. tropicalis strain. The results suggest that the endogenous tRNAGly and the CRISPRi system have great potential for metabolic engineering of C. tropicalis. IMPORTANCE In the nonmodel yeast Candida tropicalis, a lack of available RNA polymerase type III (Pol III) promoters hindered the development of guide RNA (gRNA) expression platforms for the establishment of CRISPR-Cas-mediated genome editing and silencing strategies. Here, a tRNA:gRNA platform was constructed. We show that this platform allows efficient and precise expression and processing of different gRNAs from a single polycistronic gene capable of mediating multi-gene editing in combination with CRISPR-Cas9. Furthermore, in combination with dCas9, the tRNA:gRNA platform was efficiently used for silencing of exogenous and endogenous genes, representing the first CRISPR interference tool (CRISPRi) in C. tropicalis. Importantly, the established CRISPRi-tRNA:gRNA tool was also used for metabolic engineering by regulating ß-carotene biosynthesis in C. tropicalis. The results suggest that the tRNA:gRNA platform and the CRISPRi system will further advance the application of the CRISPR-Cas-based editing and CRISPRi systems for metabolic engineering in C. tropicalis.

3.
Anal Chim Acta ; 1209: 339509, 2022 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-35569843

RESUMO

Polyoxometalates (POMs) as metal-oxide anions have exceptional properties like high negative charges, remarkable redox abilities, unique ligand properties and availability of organic grafting. Moreover, the amenability of POMs to modification with different materials makes them suitable as precursors to further obtain new composites. Due to their unique attributes, POMs and their composites have been utilized as adsorbents, electrodes and catalysts in extraction, and electrochemical and optical detection methods, respectively. A survey of the recent progress and developments of POM-based materials in these methods is therefore desirable, and should be of great interest. In this review article, POM-based materials, their properties as well as their identification methods, and analytical applications as adsorbents, electrodes and catalysts, and corresponding mechanisms of action, where relevant, are reviewed. Some current issues of the utilization of these materials and their future prospects in analytical chemistry are discussed.

4.
Front Microbiol ; 13: 869931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572672

RESUMO

Background and Objective: An increasing number of evidence has revealed that the gut microbiome functions in immunity, inflammation, metabolism, and homeostasis and is considered to be crucial due to its balance between human health and diseases such as cancer, leading to the emergence of treatments that target intestinal microbiota. Probiotics are one of them. However, many challenges remain regarding the effects of probiotics in cancer treatment. Berberine (BBR), a natural extract of Rhizoma Coptidis and extensively used in the treatment of gastrointestinal diseases, has been found to have antitumor effects in vivo and in vitro by many recent studies, but its definite mechanisms are still unclear. This study aimed to explore the inhibitory effect of BBR and probiotics on the growth of colon cancer cells in vitro and in vivo, and the regulatory influence on the gut microbiome and butyrate production. Methods: Colon cancer cell line HT29 was used to establish a xenograft model of nude mice and an in vitro model. A total of 44 nude mice and HT29 cells were divided into control, model, model + BBR, model + probiotics, and model + combination of BBR with probiotics (CBPs). Live combined Bifidobacterium, Lactobacillus, and Enterococcus powder (LCBLEP) was used as a probiotic preparation. LCBLEP was cultured in the liquid medium under anaerobic conditions (the number of viable bacteria should reach 1 × 108CFU), and the supernatant was collected, and it is called probiotic supernatant (PS). Model + BBR and model + probiotics groups were treated with BBR and LCBLEP or PS for 4 weeks in vivo or 48, 72, and 96 h in vitro, respectively. Tumor volume or cell proliferation was measured. Gut microbiota was pyrosequenced using a 16S rDNA amplicon. HDAC1 mRNA level in HT29 cells and sodium butyrate (SB) expression in the serum of mice was detected by QPCR and ELISA. Results: The treatment of BBR and CBP reduced the growth of neoplasms in mice to a different extent (p > 0.05), especially at 14 days. The inhibitory effect of LCBLEP on tumor growth was more significant, especially at 11-21 days (p < 0.05). Inhibition of BBR on in vitro proliferation was concentration-dependent. The suppression of 75% probiotic supernatant (PS) on the proliferation was the most significant. The supplement of LCBLEP significantly increased the richness and evenness of the gut microbe. BBR dramatically increased the abundance of Bacteroidetes and Proteobacteria, with reduced Ruminococcus, followed by the LCBLEP. The LCBLEP reduced the relative abundance of Verrucomicrobia and Akkermansia, and the CBP also promoted the relative level of Bacteroidetes but reduced the level of Verrucomicrobia and Akkermansia. BBR and LCBLEP or CBP improved the alpha and beta diversity and significantly affected the biomarker and metabolic function of the gut microbe in nude mice with colon cancer. The level of HDAC1 mRNA was reduced in HT29 cells treated with BBR or PS (p < 0.05), the mice treated with BBR revealed a significantly increased concentration of SB in serum (p < 0.05), and the inhibitory effect of SB on the proliferation of HT29 cells was stronger than panobinostat and TSA. Conclusion: Although the combination of BBR and probiotics has no advantage in inhibiting tumor growth compared with the drug alone, BBR can be used as a regulator of the intestinal microbiome similar to the probiotics by mediating the production of SB during reducing the growth of colon cancer.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35526532

RESUMO

INTRODUCTION: Studies indicate a very low rate of SARS-CoV-2 detection in the placenta or occasionally a low rate of vertical transmission in COVID-19 pregnancy. SARS-CoV-2 Delta variant has become a dominant strain over the world and possesses higher infectivity due to mutations in its spike receptor-binding motif. CASE PRESENTATION: To determine whether SARS-CoV-2 Delta variant has increased potential for placenta infection and vertical transmission, we analyzed SARS-CoV-2 infection in the placenta, umbilical cord, and fetal membrane from a case that unvaccinated mother and her neonate were COVID-19 positive. A 35-year-old primigravida with COVID-19 underwent an emergent cesarean delivery due to placental abruption in the setting of premature rupture of membranes. The neonate tested positive for SARS-CoV-2 within the first 24 hours, and then again on days of life 2, 6, 13, and 21. The placenta exhibited intervillositis, increased fibrin deposition, and syncytiotrophoblast necrosis. Sequencing of viral RNA from fixed placental tissue revealed SAR-CoV-2 B.1.167.2 (Delta) variant. Both spike protein and viral RNA were abundantly present in syncytiotrophoblasts, cytotrophoblasts, umbilical cord vascular endothelium, and fetal membranes. DISCUSSION/CONCLUSION: We report with strong probability the first SARS-CoV-2 Delta variant transplacental transmission. Placental cells exhibited extensive apoptosis, senescence, and ferroptosis after SARS-CoV-2 Delta infection.

6.
Genomics ; 114(3): 110379, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35526740

RESUMO

Advanced maternal aging has become a worldwide public health issue contributing to female fertility decline. To provide a complete landscape of transcriptome and epigenetic changes during oocyte aging and maturation, we applied a parallel bimodal genomics approach to parallel transcriptome and methylome profiles of mouse oocytes at single-cell and single-base resolution. Age-associated gene expression changes were associated with defective spindle assembly and mitochondrial dysfunction. Parallel sequencing data suggested aged-related defects in mRNA degradation and methylome remodelling during oocyte maturation. Differentially methylated region in aged mature oocyte was associated with trimethylation of Histone H3 at Lysine 4. More importantly, RNA expression-based prediction model for assessing maturation and oocytes age. Taken together, our work provides a better understanding of molecular mechanisms during mouse oocyte aging, points a new direction of oocyte quality assessment and paves the way for developing novel treatments to improve oocyte quality.

7.
Zhongguo Zhen Jiu ; 42(5): 590-4, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35543955

RESUMO

The existing problems in the outcomes of randomized controlled trials (RCTs) of acupuncture for vascular cognitive impairment (VCI) during recent five years are analyzed and suggestions are proposed. The RCTs of acupuncture for VCI were selected in PubMed, EMbase, Cochrane Library, Clinical Trials, CNKI database, Wanfang database, VIP database, SinoMed database and Chinese Clinical Trial Registry (ChiCTR) from January 1, 2015 to September 14, 2020. The outcomes were extracted and analyzed. As a result, 21 RCTs were included and the outcomes used were divided into 9 categories: clinical symptom/sign indexes, quality of life indexes, neuroimaging indexes, neuroelectrophysiology indexes, blood biochemical indexes, hemorheology indexes, TCM syndrome score indexes, clinical efficacy indexes, and safety indexes. Among them, the top three of the most used outcomes were clinical symptoms/signs indexes (21, 100.0%), clinical efficacy indexes (14, 66.7%) and quality of life indexes (12, 57.1%). In the RCTs of acupuncture for VCI, attention should be paid to distinguish the primary outcomes and secondary outcomes, adopt objective and standardized efficacy evaluation, and give consideration to report the outcomes of safety, health economic and TCM characteristic indexes.


Assuntos
Terapia por Acupuntura , Disfunção Cognitiva , Disfunção Cognitiva/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Life Sci ; : 120611, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35526594

RESUMO

AIMS: Organophosphorus pesticide diazinon (DZN) has adverse effects on animals and humans by direct contact or the spread of food chain. The antioxidant melatonin has protective effects on female reproduction. This study aimed to explore the effects of DZN on meiosis maturation in mouse cumulus oocyte complexes (COCs) and the effects of melatonin. MAIN METHODS: Different concentrations of DZN and melatonin were added during the in vitro maturation of COCs. Then we detected the extrusion rate of the first polar body, the number of sperms binding to oocyte, mitochondrial membrane potential, reactive oxygen species (ROS), early apoptosis. Subsequently, the expression of Juno, CX37, CX43 and ERK1/2 were detected by immunofluorescence staining and Western blotting. KEY FINDINGS: DZN exposure results in the failure of nuclear and cytoplasmic maturation of oocyte meiosis. Destruction of repositioning and function of mitochondria increases the levels of ROS and early apoptosis. The DZN-exposed oocytes express less Juno resulting to bind less sperms than normal. The loss of gap junctions and failure to activate ERK1/2 also contribute to the failure of cytoplasmic maturation. All these ultimately lead to the poor oocyte quality and low fertility. Appropriate melatonin can effectively restore all these defects. SIGNIFICANCE: Under DZN exposure, melatonin can significantly improve the quality of oocytes, and melatonin promotes oocyte maturation by protecting gap junction and restoring ERK1/2 pathway, which is a new breakthrough for improving female fertility.

9.
J Sep Sci ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524724

RESUMO

A method is firstly established for the separation and determination of fenpropathrin enantiomer residues in apple puree, strawberry puree, and tomato puree considered as a supplementary food for infants by supercritical fluid chromatography. After the sample was extracted with acetonitrile and cleaned up by a solid phase extraction column, then it's separated by a CHIRALPAK AD-3 chiral column with a gradient elution at a flow rate of 1.0 mL/min using methanol and supercritical carbon dioxide as the mobile phase, detected by ultraviolet detector at 230 nm wavelength and quantified with the external standard method. The limits of quantification of the two fenpropathrin enantiomers were both 0.2 mg/kg, the linear ranges were 1.0-20.0 mg/L with linear correlation coefficients greater than 0.9992, the recoveries in the spiked samples at 0.2, 0.4 and 2.0 mg/kg were from 80.6% to 105%, and the relative standard deviation reached 2.6%-7.7%. This method has the advantages of convenient operation, good resolution and environmental protection, which can satisfy the requirement of determination for fenpropathrin enantiomer residues in fruit and vegetable puree as a supplementary food for infants. This article is protected by copyright. All rights reserved.

10.
Anal Chem ; 94(20): 7229-7237, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35532756

RESUMO

In order to solve the problem of difficult separation of various biogenic amines (BAs), which have similar structures or very different polarities, in gentamicin, by conventional liquid chromatography, a new ultrahigh-performance supercritical fluid chromatography (UHPSFC) method was developed. In this method, 10 BAs were derivatized precolumn using dansyl chloride and separated using a UHPSFC system. By computational simulation, complete separation of 10 BAs was successfully achieved. Detection was performed using a photodiode array (PDA) and single-quadrupole mass spectrometry (MS) together with electrospray ionization (ESI). A wide linear range (10-2500 ng/mL) was achieved, with the limits of detection (LODs) between 1.2 and 10.0 ng/mL and the limits of quantification (LOQs) between 5.0 and 25.0 ng/mL. Apart from high sensitivity, this UHPSFC-PDA/ESI-MS detection method also displayed high accuracy, the matrix effect was reduced by an appreciable extent, and the recovery rates of the 10 BAs were between 84.1 and 117.1%. For comparison, high-performance liquid chromatography-tandem mass spectrometry (MS/MS) was also used for the detection of underivatized BAs in gentamicin, showing good linearity and high sensitivity (LODs from 0.05 to 1.00 ng/mL and LOQs from 1.00 to 12.50 ng/mL) for all BAs except for spermine and spermidine. Although single-quadrupole MS is inferior to MS/MS in terms of sensitivity, the UHPSFC method could detect more BAs. It also achieved the quantification limits required for impurity determination, demonstrating a potential strategy to offer a map overview of possible BA presence in fermentation antibiotics.

11.
J Clin Lab Anal ; 36(5): e24396, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35373420

RESUMO

BACKGROUNDS: As a regulator of cell cycle, cell division cycle-associated 5 (CDCA5) is involved in the progression of various malignant tumors. However, the potential relationship between CDCA5 and lung cancer has not been reported. METHODS: In our study, we analyzed the expression of CDCA5 in a variety of malignant tumors, performed Kaplan-Meier survival analysis of lung adenocarcinoma (LUAD), explored the potential relationship between CDCA5 expression and clinicopathological characteristics, assessed the predictive capability of at different stages of clinicopathological characteristics, revealed the enriched functions and signaling pathways among LUAD paitents with high CDCA5 expression, and investigated the correlation between PD-1, PD-L1, and CDCA5 through bioinformatics analyses. Subsequently, we performed quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) to demonstrate that CDCA5 mediates the p53-p21 pathway and regulates the cell cycle. RESULT: CDCA5 is probably involved in the occurrence and development of NSCLC, and function as a reliable biomarker for predicting the survival outcomes of patients with early stage of patients with LUAD. Furthermore, CDCA5 may be a promising indicator of immunotherapy efficacy. In addition, silencing the expression of CDCA5 significantly increased the proportion of apoptotic NSCLC cells, and caused NSCLC cells to be arrested in the G1 phase. CONSLUSION: In conclusion, CDCA5 regulated the cell cycle of NSCLC cells by mediating the p53-p21 signaling pathway, participating in the development and progression of NSCLC patients.

12.
Gene ; 829: 146511, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35447234

RESUMO

Zearalenone (ZEN), a common non-steroidal estrogenic mycotoxin of the Fusarium genus, is one of the most frequent and powerful contaminant of grains and cereal products representing a serious threat for people and livestock health. In fact, ZEN causes cytotoxicity and genotoxicity in a variety of cell types at least in part through binding to estrogen receptors (ERs). The main pathways through which ZEN induces such effects remain, however, elusive. In particular, how the mycotoxin causes DNA damage, dysregulates DNA repair mechanisms, changes epigenome of targeted cells and, not least, affects chromatin conformation and non-coding RNA (ncRNA), is unclear. In the present paper, following extensive review of the literature about such ZEN effects and our own experience in studying the effects of this compound on reproductive processes, we propose that increased production of reactive oxygen species (ROS) and consequently oxidative stress (OS) are central in ZEN genotoxicity. Besides to shed light on the action mechanisms of the mycotoxin, this notion might help to develop effective strategies to counteract its deleterious biological effects.

14.
World J Clin Cases ; 10(9): 2733-2742, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35434111

RESUMO

BACKGROUND: Despite advances in medical therapy for Crohn's disease (CD), most patients with CD require repeated resection surgeries. AIM: To analyze the perforating and nonperforating indications of repeated CD operations and identify the anastomosis characteristics for postoperative CD. METHODS: We retrospectively reviewed 386 patients who underwent at least one resection for CD between 2003 and 2013.Clinical characteristics of each surgery were collected. Univariate and multivariate analyses were performed to determine risk factors for recurrence. RESULTS: The indication for reoperation in CD tends to be the same as that for primary operation, i.e., perforating disease tends to represent as perforating disease and nonperforating as nonperforating. Concordance was found between the first surgery and second surgery in terms of the indication for the operation (P = 0.006), and the indication for the third surgery was also correlated with that for the second surgery (P = 0.033). Even if the correlation of surgical indications between repeated operations, the rate of perforating indication for the second and third surgeries was significantly higher than that of the first surgery. In addition, the presence of perforating CD was a predictor of recurrence for both the first and second surgeries. Moreover, anastomotic lesions were the most common sites of recurrence after the operation. Based on the importance of anastomosis, anastomosis might be a new type of disease location for the classification of postoperative CD. CONCLUSION: CD not only has stable characteristics but also progresses chronically. Perforation is a progressive surgical indication for Crohn's disease. For CD after surgery, anastomosis may be a new classification of disease location.

15.
Mol Med ; 28(1): 45, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468731

RESUMO

BACKGROUND: Clinical data suggest that male reproductive dysfunction especially infertility is a critical issue for type 1 diabetic patient (T1D) because most of them are at the reproductive age. Gut dysbiosis is involved in T1D related male infertility. However, the improved gut microbiota can be used to boost spermatogenesis and male fertility in T1D remains incompletely understood. METHODS: T1D was established in ICR (CD1) mice with streptozotocin. Alginate oligosaccharide (AOS) improved gut microbiota (fecal microbiota transplantation (FMT) from AOS improved gut microbiota; A10-FMT) was transplanted into the T1D mice by oral administration. Semen quality, gut microbiota, blood metabolism, liver, and spleen tissues were determined to investigate the beneficial effects of A10-FMT on spermatogenesis and underlying mechanisms. RESULTS: We found that A10-FMT significantly decreased blood glucose and glycogen, and increased semen quality in streptozotocin-induced T1D subjects. A10-FMT improved T1D-disturbed gut microbiota, especially the increase in small intestinal lactobacillus, and blood and testicular metabolome to produce n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to ameliorate spermatogenesis and semen quality. Moreover, A10-FMT can improve spleen and liver functions to strengthen the systemic environment for sperm development. FMT from gut microbiota of control animals (Con-FMT) produced some beneficial effects; however, to a smaller extent. CONCLUSIONS: AOS-improved gut microbiota (specific microbes) may serve as a novel, promising therapeutic approach for the improvement of semen quality and male fertility in T1D patients via gut microbiota-testis axis.


Assuntos
Diabetes Mellitus Tipo 1 , Microbioma Gastrointestinal , Animais , Diabetes Mellitus Tipo 1/terapia , Transplante de Microbiota Fecal , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Análise do Sêmen , Estreptozocina , Testículo
16.
Nat Biomed Eng ; 6(4): 339-350, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35437313

RESUMO

Mitochondrial replacement therapy (MRT) has been used to prevent maternal transmission of disease-causing mutations in mitochondrial DNA (mtDNA). However, because MRT requires nuclear transfer, it carries the risk of mtDNA carryover and hence of the reversion of mtDNA to pathogenic levels owing to selective replication and genetic drift. Here we show in HeLa cells, mouse embryos and human embryos that mtDNA heteroplasmy can be reduced by pre-labelling the mitochondrial outer membrane of a donor zygote via microinjection with an mRNA coding for a transmembrane peptide fused to an autophagy receptor, to induce the degradation of the labelled mitochondria via forced mitophagy. Forced mitophagy reduced mtDNA carryover in newly reconstructed embryos after MRT, and had negligible effects on the growth curve, reproduction, exercise capacity and other behavioural characteristics of the offspring mice. The induction of forced mitophagy to degrade undesired donor mtDNA may increase the clinical feasibility of MRT and could be extended to other nuclear transfer techniques.


Assuntos
Terapia de Substituição Mitocondrial , Animais , DNA Mitocondrial/genética , Células HeLa , Heteroplasmia , Humanos , Camundongos , Mitocôndrias/genética , Terapia de Substituição Mitocondrial/métodos , Mitofagia/genética
17.
Front Pharmacol ; 13: 839305, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401232

RESUMO

Background: Xingnaojing injection (XNJ) is derived from a traditional Chinese prescription named Angong Niuhuang pill. As an adjuvant treatment widely used in acute ischemic stroke (AIS), XNJ has proven to be effective with certain clinical evidence. The aim of this study is to collect the latest evidence and evaluate efficacy and safety of XNJ for emergency treatment of AIS. Methods: We searched seven literature databases and two clinical trial registries from their inception to November 14, 2021 for randomized controlled trials (RCTs) examining the efficacy of XNJ for AIS. Two reviewers independently selected relevant trials, extracted data, and assessed the risk of bias. We pooled data into a meta-analysis using RevMan 5.4 software. Results: Thirty-eight RCTs were included in this review, with a total of 3,677 participants. XNJ plus conventional treatments (CTs) showed a significant advantage, compared with CTs alone, in improving functional independence at 14 days (RR = 1.70, 95% CI = 1.03 to 2.81, p = 0.04), neurological function (MD NIHSS < 6h = -3.81, 95% CI = -5.25 to -2.38, p < 0.00001; MD NIHSS < 24h = -3.75, 95% CI = -4.92 to -2.59, p < 0.00001; MD NIHSS < 72h = -3.74, 95% CI = -5.48 to -2.00, p < 0.0001; MD NIHSS < 14d = -1.97, 95% CI = -3.25 to -0.69, p = 0.003), and activities of daily living on the Barthel index (MD BI-14day = 9.97, 95% CI = 9.29 to 10.65, p < 0.00001; MD BI-30day = 10.04, 95% CI = 5.82, to 14.26, p < 0.00001). In addition, the results showed that XNJ plus CTs was superior to CTs alone in reducing IL-6, TNF-α, hs-CRP, and MMP-9. Regarding safety of XNJ, the incidence of adverse reactions in the XNJ group was lower than that in the control group (RR = 0.57, 95% CI = 0.38 to 0.87, p = 0.009). The certainty of evidence was evaluated as low or very low for all. Conclusion: XNJ appears to be effective and safe for emergency treatment of AIS. The first 72 h after the onset of stroke, in particular the first 6 hours, may be the optimum initiation time. However, further high-quality RCTs are warranted to determine an appropriate initiation time. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=233211], identifier [CRD42021233211].

18.
Hum Pathol ; 124: 85-95, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35378115

RESUMO

Most spermatocytic tumors (STs) have an excellent prognosis. In rare instances, metastatic disease has been documented. However, it is unclear if aggressive tumors have specific molecular alterations. Herein, we have studied primary STs with (n = 4) and without (n = 3) anaplastic features, including single-nucleotide polymorphism microarrays for 5 ST (nonanaplastic: 3; anaplastic: 2). The mean age at orchiectomy and tumor size was 49 years and 6.5 cm, respectively. Lymphovascular invasion and necrosis were identified in 3 (of 4, 75%) anaplastic STs, including one with clinically metastatic disease and one with locally aggressive disease. None of the cases in this study exhibited sarcomatoid change. The mean mitotic count was higher in anaplastic tumors (59/10 versus 10/10 high-power fields). All STs in this study were positive for SALL4 and CD117 and negative for OCT3/4 and CD30 (7/7, 100%). SSX-C positivity was identified in all but the locally aggressive anaplastic ST (5 of 6, 83%). All STs showed a consistent gain of chromosome 9 including the locus for the DMRT1 gene (5 of 5 cases, 100%), while gains of chromosome 12p were only seen in 2 (of 2) anaplastic variants. Gains of 12p in anaplastic STs may represent a biomarker of transformation into more aggressive tumors. Alternatively, STs with gain of 12p may represent an intermediate state between type II and type III germ cell tumors. Future studies are needed to validate whether gain of 12p is a consistent feature of STs with anaplastic morphology and its association with aggressive clinical behavior.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Aberrações Cromossômicas , Cromossomos , Cromossomos Humanos Par 12 , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Masculino , Neoplasias Embrionárias de Células Germinativas/genética , Seminoma/patologia , Neoplasias Testiculares/patologia
19.
Environ Pollut ; 305: 119269, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405219

RESUMO

Endocrine-disrupting chemicals (EDCs) are ubiquitous in daily life, but their harmful effects on the human body have not been fully explored. Recent studies have shown that EDCs exposure could lead to infertility, menstrual disorder and menopause, resulting in subsequent effects on female health. Therefore, it is of great significance to clarify and summarize the impacts of EDCs on ovarian aging for explaining the etiology of ovarian aging and maintaining female reproductive health. Here in this review, we focused on the impacts of ten typical environmental contaminants on the progression of ovarian aging during adult exposure, including epidemiological data in humans and experimental models in rodents, with their clinical phenotypes and underlying mechanisms. We found that both persistent (polychlorinated biphenyls, perfluoroalkyl and polyfluoroalkyl substances) and non-persistent (phthalates) EDCs exposure could increase an overall risk of ovarian aging, leading to the diminish of ovarian reserve, decline of fertility or fecundity, irregularity of the menstrual cycle and an earlier age at menopause, and/or premature ovarian insufficiency/failure in epidemiological studies. Among these, the loss of follicles can also be validated in experimental studies of some EDCs, such as BPA, phthalates, parabens and PCBs. The underlying mechanisms may involve the impaired ovarian follicular development by altering receptor-mediated pro-apoptotic pathways, inducing signal transduction and cell cycle arrest and epigenetic modification. However, there were inconsistent results in the impacts on fertility/fecundity, menstrual/estrous cycle and hormone changes response to different EDCs, and differences between human and animal studies. Our review summarizes the current state of knowledge on ovarian disrupters, highlights their risks to ovarian aging and identifies knowledge gaps in humans and animals. We therefore propose that females adopt healthy lifestyle changes to minimize their exposure to both persistent and non-persistent chemicals, that have the potential damage to their reproductive function.


Assuntos
Disruptores Endócrinos , Reserva Ovariana , Bifenilos Policlorados , Envelhecimento , Animais , Disruptores Endócrinos/toxicidade , Exposição Ambiental , Feminino , Ovário , Bifenilos Policlorados/farmacologia
20.
Sci Total Environ ; : 155130, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35405229

RESUMO

Comprehensive knowledge on the biotransformation of tetracycline (TC) is critical for the improvement of TC removal in the bioremediation process. This work isolated a novel TC-degrading bacterial strain Alcaligenes sp. T17 and explored its degradation ability under different conditions. Temperature and pH could affect the degradation efficiency, and higher temperature as well as neutral and weakly acidic conditions were conducive to the biotransformation. Response surface methodology predicted the maximum degradation rate of TC (94.35%) under the condition of 25.15 mg/L TC, pH 7.23, and inoculation dosage 1.17% at 40 °C. According to the result of disk diffusion tests, the biodegradation products had lower antimicrobial potency than the parent compound. Five potential biodegradation products were identified, and a possible degradation pathway (degrouping, oxidation and ring-opening) was proposed. The draft genome of strain T17 was also determined. Genomic analysis indicated that strain T17 harbored multiple genes that participated in the metabolism of aromatic compounds as well as genes encoding oxygenases. These functional genes may be relevant to TC biotransformation. This study could provide new insights towards the biotransformation of TC mediated by bacteria.

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