Publications by authors named "Jinbo Li"

90 Publications

Effects of secondary polyethylene microplastic exposure on crucian (Carassius carassius) growth, liver damage, and gut microbiome composition.

Sci Total Environ 2021 Aug 19;802:149736. Epub 2021 Aug 19.

School of Chemistry and Chemical Engineering, Xi'an Shiyou University, Xi'an 710000, China.

Microplastics (MPs) have been found in the natural environment and even in the organs of fish, which is attracting worldwide attention. In this study, agricultural film was milled to simulate secondary polyethylene microplastics (PE-MPs) to evaluate their effect and toxicity on the growth, liver damage, and gut microbiome composition of crucian (Carassius carassius), a common freshwater fish, after 30 days of feed exposure. Three fish feed treatments with different PE-MPs concentrations, low, medium, and high, whose PE-MPs intake was 6.38, 12.18, and 22.33 mg MPs/fish/day, respectively, were used. The results indicated that crucian growth was promoted in the low and medium PE-MPs groups due to the increase in Firmicutes and decrease in Bacteroidetes, probably resulting in obesity and lipid accumulation, while the growth rate of crucians in the high PE-MPs group showed a clear downward trend. Severe liver damage was observed in PE-MPs-treated groups. Disordered liver tissue and necrosis of pancreatic acinar epithelial cells were observed in the medium and high PE-MPs groups compared with those of the control group. The gut microbiome composition of crucians showed significant alteration, and some harmful bacteria were found in the gut following PE-MPs exposure. Alpha diversity indices revealed that the diversity of the gut microbiome rose markedly in the low, medium, and high PE-MPs groups. This study suggests that MPs adversely affect crucian growth and health, with increased disease risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.149736DOI Listing
August 2021

Doxorubicin-Near infrared dye conjugate induces immunogenic cell death to enhance cancer immunotherapy.

Int J Pharm 2021 Sep 19;607:121027. Epub 2021 Aug 19.

Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China. Electronic address:

Cancer immunotherapy often fails to result in a favorable outcome owing to poor activation of immune response, the immunosuppressive tumor microenvironment, and systemic toxicity. In this study, indocyanine green (ICG) was conjugated with doxorubicin (DOX) using a hydrazone linker (DOX-ICG). Results of our in vitro and in vivo studies indicated that DOX-ICG could trigger powerful immunogenic cell death (ICD) of tumor cells. Moreover, its use in combination with immune checkpoint inhibitors could effectively inhibit both primary and abscopal tumors growth and suppress tumor metastasis. Therefore, this simple, safe, and efficient prodrug shows great potential for use in photo-activated chemo-immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.121027DOI Listing
September 2021

Defecation delay in patients after lung tumor surgery: a prospective nested case-control study.

Ann Transl Med 2021 Jun;9(12):980

State Key Laboratory of Oncology in South China, Guangzhou, China.

Background: Defecation delay (greater than or equal to 3 days post-surgery) is a common symptom in patients after lung tumor surgery. This study investigated the incidence and relevant risk factors of defecation delay in patients after lung tumor surgery.

Methods: Between October 2019 and March 2020, a prospective nested case-control study was conducted in 80 patients who received lung tumor surgery in the Department of Thoracic Surgery at the Sun Yat-sen University Cancer Center. According to the Rome III criteria for functional constipation and the accepted definitions in the literature, patients with defecation delay time greater than or equal to 3 days post-surgery were classified as the defecation delay group, and the remaining patients were considered the control group. A questionnaire survey was conducted to explore the trait of the stool, defecation time, postoperative activity, diet, and perioperative pain score. Statistical analyses were performed to compare the risk factors affecting defecation time in the two groups.

Results: Out of 80 patients, a total of 44 patients (44/80) experienced defecation delay after the operation. Univariate analysis showed that there were significant differences between the two groups in operation methods (P<0.029), postoperative stool trait (P<0.001), difficulty in defecation (P<0.01), and perioperative pain score (P=0.0178), suggesting that change of stool characteristics and pain were possible factors causing defecation delay. Multivariate analysis also revealed significant differences between the two groups in the postoperative pain score on the first day post-surgery (P=0.03).

Conclusions: Defecation delay is a common symptom in patients after lung cancer surgery, and is related to operation method, pain score, and changes in stool characteristics. This study identified that minimally invasive surgery, postoperative pain relief treatment, and health education may play an important role in preventing delayed defecation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-21-2468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267306PMC
June 2021

Patterns of Immune Infiltration in Endometriosis and Their Relationship to r-AFS Stages.

Front Genet 2021 18;12:631715. Epub 2021 Jun 18.

Department of Gynecology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Endometriosis (EMS) is an estrogen-dependent disease in which endometrial glands and stroma arise outside the uterus. Current studies have suggested that the number and function of immune cells are abnormal in the abdominal fluid and ectopic lesion tissues of patients with EMS. The developed CIBERSORT method allows immune cell profiling by the deconvolution of gene expression microarray data. By applying CIBERSORT, we assessed the relative proportions of immune cells in 68 normal endometrial tissues (NO), 112 eutopic endometrial tissues (EU) and 24 ectopic endometrial tissues (EC). The obtained immune cell profiles provided enumeration and activation status of 22 immune cell subtypes. We obtained associations between the immune cell environment and EMS r-AFS stages. Macrophages were evaluated by immunohistochemistry (IHC) in 60 patients with ovarian endometriomas. Total natural killer (NK) cells were significantly decreased in EC, while plasma cells and resting CD4 memory T cells were increased in EC. Total macrophages in EC were significantly increased compared to those of EU and NO, and M2 macrophages were the primary macrophages in EC. Compared to those of EC from patients with r-AFS stage I ~ II, M2 macrophages in EC from patients with stage III ~ IV were significantly increased. IHC experiments showed that total macrophages were increased in EC, with M2 macrophages being the primary subtype. Our data demonstrate that deconvolution of gene expression data by CIBERSORT provides valuable information about immune cell composition in EMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.631715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249861PMC
June 2021

Bisphenols disrupt thyroid hormone (TH) signaling in the brain and affect TH-dependent brain development in Xenopus laevis.

Aquat Toxicol 2021 Aug 24;237:105902. Epub 2021 Jun 24.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, No. 18, Shuangqing Road, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

There is concern about adverse effects of thyroid hormone (TH) disrupting chemicals on TH-dependent brain development. Bisphenol A (BPA) and its analogues, such as bisphenol F (BPF), are known to have the potential to interfere with TH signaling, but whether they affect TH-dependent brain development is not yet well documented. Here, we conducted the T3-induced Xenopus laevis metamorphosis assay, a model for studying TH signaling disruption, to investigate the effects of BPA and BPF (10-1000 nM) on TH signaling in brains and subsequent brain development. While 48-hr treatment with 1 nM T3 dramatically upregulated TH-response gene expression in X. laevis brains at stage 52, 1000 and/or 100 nM BPA also caused significant transcriptional up-regulation of certain TH-response genes, whereas BPF had slighter effects, suggesting limited TH signaling disrupting activity of BPF in brains relative to BPA at the lack of TH. In the presence of 1 nM T3, 1000 and/or 100 nM of BPF as well as BPA antagonized T3-induced TH-response gene expression, whereas lower concentrations agonized T3 actions on certain TH-response genes, displaying an apparently biphasic effect on TH signaling. After 96 h exposure, T3 induced brain morphological remodeling coupled with cell proliferation and neuronal differentiation, whereas both BPA and BPF generally antagonized T3-induced changes in a concentration-dependent manner, with weak or no effects of bisphenol exposure alone. Overall, all results show that BPA and BPF interfered with TH signaling in Xenopus brains, especially in the presence of TH, and subsequently affected TH-dependent brain development. Given the evolutionary conservation of TH-dependent brain development among vertebrates, our findings from X. laevis warrant further studies to reveal potential influences of bisphenols on TH-dependent brain development in higher vertebrates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aquatox.2021.105902DOI Listing
August 2021

Spherical Nucleic Acids for Near-Infrared Light-Responsive Self-Delivery of Small-Interfering RNA and Antisense Oligonucleotide.

ACS Nano 2021 Jun 25. Epub 2021 Jun 25.

State Key Laboratory of Analytical Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.

Herein, we developed a photolabile spherical nucleic acid (PSNA) for carrier-free and near-infrared (NIR) photocontrolled self-delivery of small-interfering RNA (siRNA) and antisense oligonucleotide (ASO). PSNA comprised a hydrophilic siRNA shell with a hydrophobic core containing a peptide nucleic acid-based ASO (pASO) and NIR photosensitizer (PS). The incorporation of a singlet oxygen (O)-cleavable linker between the siRNA and pASO allowed on-demand disassembly of PSNA in tumor cells once O was produced by the inner PS upon NIR light irradiation. The generated O could also concurrently promote lysosomal escape of the released siRNA and pASO to reach cytosolic targets. Both and results demonstrated that, under NIR light irradiation, PSNA could suppress hypoxia inducible factor-1α (HIF-1α) and B-cell lymphoma 2 (Bcl-2) for gene therapy (GT), which further combined photodynamic therapy (PDT) favored by the released PS to inhibit tumor cell growth. Given its carrier-free, NIR-sensitive, designable, and biocompatible merits, PSNA represents a promising self-delivery nanoplatform for cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.1c03072DOI Listing
June 2021

Enhanced adsorption of polystyrene nanoplastics (PSNPs) onto oxidized corncob biochar with high pyrolysis temperature.

Sci Total Environ 2021 Aug 16;784:147115. Epub 2021 Apr 16.

College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642, PR China; College of Resource and Environmental Engineering, Jiangxi University of Science and Technology, Ganzhou, Jiangxi 341000, PR China.

Plastic pollution has become a global threat in the natural environment, and an urgent remedial measure is needed to reduce the negative effects caused by plastic pollutants. In the current study, the effects of pyrolysis temperature (500 °C, 700 °C, and 900 °C) and aging on the adsorption of polystyrene nanoplastics (PSNPs) onto corncob biochar were systematically assessed with kinetic, isotherm, pH-dependent adsorption experiments, FTIR and XPS spectroscopy, and DLVO calculations. The oxidation was done with 5% of HNO/HSO to simulate long-term oxidative aging of biochar in the environment. The results showed that the specific surface area, hydrophobicity, and aromaticity of biochar increased with pyrolysis temperature, whereas the specific surface area and amounts of oxygen-containing groups increased after oxidation. The adsorption mechanism of PSNPs onto the biochar was explored based on the correlation between biochar properties and adsorption parameters derived from adsorption isotherms. Overall, the adsorption capacity of biochar for PSNPs increased with increased pyrolysis temperature and after aging. While the increase of specific surface area was considered the major factor leading to the increase of the adsorption, the variation in surface properties also played an important role. Pore filling, hydrophobic interaction, and hydrogen bonding may all be involved in PSNPs adsorption to biochar. However, the hydrophobic interaction might be more important for the fresh biochar, whereas hydrogen bonding involving oxygen-containing groups might make a bigger contribution to PSNPs adsorption to oxidized biochar. The pH experiments revealed that PSNPs adsorption decreased in general with the increase of pH, indicating that electrostatic repulsion played a vital role in the PSNPs adsorption process. The results of this study indicate that biochar can be potentially applied to immobilize plastic particles in terrestrial ecosystems such as in soil or groundwater, and the immobilization could be enhanced via artificial oxidation or aging of biochar in the natural environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.147115DOI Listing
August 2021

Low dose shikonin and anthracyclines coloaded liposomes induce robust immunogenetic cell death for synergistic chemo-immunotherapy.

J Control Release 2021 07 31;335:306-319. Epub 2021 May 31.

Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China. Electronic address:

Chemo-immunotherapy based on immunogenic cell death (ICD) is a promising strategy for cancer therapy. However, the effective ICD requires a high dosage of ICD stimulus, which could be associated to a dose-dependent toxicity. Therefore, in this study, a liposome remote-loaded with shikonin (a potent ICD stimulus) was developed, with the ability to effectively induce ICD at high dosage in vivo. However, a hepatotoxic effect was observed. To circumvent this problem, shikonin was combined with the anthracycline mitoxantrone or doxorubicin to develop co-loaded liposomes inducing a synergistic ICD effect and cytotoxicity to tumor cells. Cytotoxicity and uptake experiment in vitro were performed to analyze the optimal synergistic ratio of shikonin and anthracyclines based on a "formulated strategy". Interestingly, copper mediated co-loaded liposomes resulted in a pH and GSH dual-responsive release property. More importantly, pharmacokinetics and tumor biodistribution studies revealed an outstanding capacity of ratiometric delivery of dual drugs. Thus, the dual-loaded liposome enhanced the antitumor effect by the stimulation of a robust immune response at lower doses of the drugs with a higher safety compared to single-loaded liposomes. Summarized, the current work provided a reference for a rational design and development of liposomal co-delivery system of drugs and ICD-induced chemo-immunotherapy, and established a potential clinical application of shikonin-based drug combinations as a new chemo-immunotherapeutic strategy for cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2021.05.040DOI Listing
July 2021

Association between AMPKα1 gene polymorphisms and gestational diabetes in the Chinese population: A case-control study.

Diabet Med 2021 May 30:e14613. Epub 2021 May 30.

Department of Epidemiology, School of Public Health, Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, China.

Aim: The aim is to examine the association between seven candidate single nucleotide polymorphisms in AMPKα1 and gestational diabetes in Chinese people.

Method: We used a matched nested case-control study design, individuals including 334 participants with gestational diabetes and 334 healthy pregnant women. Confirmed 334 gestational diabetes cases and maternal age and district of residence matched controls (1:1) were enrolled. We examined seven candidate single nucleotide polymorphisms in AMPKα1 gene and the risk of gestational diabetes. The associations were estimated in Co-dominant, Dominant, Recessive, and Alleles models. The odds ratios (ORs) and their 95% confidence intervals (95% CI) were estimated by unconditional logistical regression as a measure of the associations between genotypes and gestational diabetes adjusting for maternal age, prepregnancy body mass index (BMI), fetal sex and parity.

Result: At the gene level, we found that AMPKα1 was associated with gestational diabetes (p = 0.008). After adjusting the covariates and multiple comparison correction, AMPKα1 (rsc1002424, rs10053664, rs13361707) polymorphisms were associated with the risk of gestational diabetes. In addition, gestational diabetes was related to the AAGGA haplotype comprising rs1002424, rs2570091, rs10053664, rs13361707 and rs3805486 in the haplotype models (p = 0.011).

Conclusions: This study provides evidence that the AMPKα1 genotypes (rs1002424 G/A, rs10053664 A/G, rs13361707 A/G) and the haplotype (AAGGA) are relevant genetic factors in a Chinese population with gestational diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dme.14613DOI Listing
May 2021

Disulfide bond based cascade reduction-responsive Pt(IV) nanoassemblies for improved anti-tumor efficiency and biosafety.

Colloids Surf B Biointerfaces 2021 Jul 15;203:111766. Epub 2021 Apr 15.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:

The platinum-based drugs prevail in the therapy of malignant tumors treatment. However, their clinical outcomes have been heavily restricted by severe systemic toxicities. To ensure biosafety and efficiency, herein, we constructed a disulfide bond inserted Pt(IV) self-assembled nanoplatform that is selectively activated by rich glutathione (GSH) in tumor site. Disulfide bond was introduced into the conjugates of oxaliplatin (IV) and oleic acid (OA) which conferred cascade reduction-responsiveness to nanoassemblies. Disulfide bond cleavage and reduction of Pt(IV) center occur sequentially as a cascade process. In comparison to oxaliplatin solution, Pt(IV) nanoparticles (NPs) achieved prolonged blood circulation and higher maximum tolerated doses. Furthermore, Oxa(IV)-SS-OA prodrug NPs exhibited potent anti-tumor efficiency against 4T1 cells and low toxicities in other normal tissues, which offers a promising nano-platform for potential clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2021.111766DOI Listing
July 2021

Species packing and the latitudinal gradient in beta-diversity.

Proc Biol Sci 2021 04 14;288(1948):20203045. Epub 2021 Apr 14.

Center of Conservation Biology, Core Botanical Gardens, Chinese Academy of Sciences, Wuhan 430074.

The decline in species richness at higher latitudes is among the most fundamental patterns in ecology. Whether changes in species composition across space (beta-diversity) contribute to this gradient of overall species richness (gamma-diversity) remains hotly debated. Previous studies that failed to resolve the issue suffered from a well-known tendency for small samples in areas with high gamma-diversity to have inflated measures of beta-diversity. Here, we provide a novel analytical test, using beta-diversity metrics that correct the gamma-diversity and sampling biases, to compare beta-diversity and species packing across a latitudinal gradient in tree species richness of 21 large forest plots along a large environmental gradient in East Asia. We demonstrate that after accounting for topography and correcting the gamma-diversity bias, tropical forests still have higher beta-diversity than temperate analogues. This suggests that beta-diversity contributes to the latitudinal species richness gradient as a component of gamma-diversity. Moreover, both niche specialization and niche marginality (a measure of niche spacing along an environmental gradient) also increase towards the equator, after controlling for the effect of topographical heterogeneity. This supports the joint importance of tighter species packing and larger niche space in tropical forests while also demonstrating the importance of local processes in controlling beta-diversity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rspb.2020.3045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059527PMC
April 2021

Jasmonic acid-responsive RRTF1 transcription factor controls DTX18 gene expression in hydroxycinnamic acid amide secretion.

Plant Physiol 2021 03;185(2):369-384

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Jasmonates (JAs) are plant hormones that regulate the biosynthesis of many secondary metabolites, such as hydroxycinnamic acid amides (HCAAs), through jasmonic acid (JA)-responsive transcription factors (TFs). HCAAs are renowned for their role in plant defense against pathogens. The multidrug and toxic compound extrusion transporter DETOXIFICATION18 (DTX18) has been shown to mediate the extracellular accumulation of HCAAs p-coumaroylagmatine (CouAgm) at the plant surface for defense response. However, little is known about the regulatory mechanism of DTX18 gene expression by TFs. Yeast one-hybrid screening using the DTX18 promoter as bait isolated the key positive regulator redox-responsive TF 1 (RRTF1), which is a member of the AP2/ethylene-response factor family of proteins. RRTF1 is a JA-responsive factor that is required for the transcription of the DTX18 gene, and it thus promotes CouAgm secretion at the plant surface. As a result, overexpression of RRTF1 caused increased resistance against the fungus Botrytis cinerea, whereas rrtf1 mutant plants were more susceptible. Using yeast two-hybrid screening, we identified the BTB/POZ-MATH (BPM) protein BPM1 as an interacting partner of RRTF1. The BPM family of proteins acts as substrate adaptors of CUL3-based E3 ubiquitin ligases, and we found that only BPM1 and BPM3 were able to interact with RRTF1. In addition, we demonstrated that RRTF1 was subjected to degradation through the 26S proteasome pathway and that JA stabilized RRTF1. Knockout of BPM1 and BPM3 in bpm1/3 double mutants enhanced RRTF1 accumulation and DTX18 gene expression, thus increasing resistance to the fungus B. cinerea. Our results provide a better understanding of the fine-tuned regulation of JA-induced TFs in HCAA accumulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/plphys/kiaa043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133619PMC
March 2021

Association of CPT1A gene polymorphism with the risk of gestational diabetes mellitus: a case-control study.

J Assist Reprod Genet 2021 Jul 9;38(7):1861-1869. Epub 2021 Mar 9.

Department of Epidemiology, Shanxi Medical University School of Public Health, Center of Clinical Epidemiology and Evidence-Based Medicine, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China.

Purpose: Gestational diabetes mellitus (GDM) is a growing public health problem worldwide and its etiology remains unclear. The pathophysiology of GDM is similar to that of type 2 diabetes (T2DM) and insulin resistance (IR) is the main reason for the development of GDM. Carnitine palmitoyltransferase 1A (CPT1A) is a candidate gene for metabolic disorders; however, the association of the CPT1A gene and GDM has not yet been studied. We aimed to explore whether single-nucleotide polymorphisms (SNPs) of the CPT1A gene could influence the risk of GDM.

Methods: We examined 18 single-nucleotide polymorphisms (SNPs) in the CPT1A gene and the risk of GDM in a nested case-control study of 334 GDM patients and 334 controls. The controls who had no GDM were randomly selected through matching to cases by age and residence.

Results: After adjusting the family history of diabetes, pre-pregnancy body mass index, and multiple comparison correction, the CPT1A rs2846194 and rs2602814 were associated with reduced GDM risk while rs59506005 was associated with elevated GDM risk. Moreover, the GGAC haplotype in the CPT1A gene (rs17399246 rs1016873 rs11228450 rs10896396) was associated with a reduced risk of GDM.

Conclusion: Our study provides evidence for an association between genetic polymorphisms in the CPT1A and the risk of GDM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10815-021-02143-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324722PMC
July 2021

Development of Testis Cords and the Formation of Efferent Ducts in Xenopus laevis: Differences and Similarities with Other Vertebrates.

Sex Dev 2020 4;14(1-6):66-79. Epub 2021 Mar 4.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China,

The knowledge of testis development in amphibians relative to amniotes remains limited. Here, we used Xenopus laevis to investigate the process of testis cord development. Morphological observations revealed the presence of segmental gonomeres consisting of medullary knots in male gonads at stages 52-53, with no distinct gonomeres in female gonads. Further observations showed that cell proliferation occurs at specific sites along the anterior-posterior axis of the future testis at stage 50, which contributes to the formation of medullary knots. At stage 53, adjacent gonomeres become close to each other, resulting in fusion; then (pre-)Sertoli cells aggregate and form primitive testis cords, which ultimately become testis cords when germ cells are present inside. The process of testis cord formation in X. laevis appears to be more complex than in amniotes. Strikingly, steroidogenic cells appear earlier than (pre-)Sertoli cells in differentiating testes of X. laevis, which differs from earlier differentiation of (pre-)Sertoli cells in amniotes. Importantly, we found that the mesonephros is connected to the testis gonomere at a specific site at early larval stages and that these connections become efferent ducts after metamorphosis, which challenges the previous concept that the mesonephric side and the gonadal side initially develop in isolation and then connect to each other in amphibians and amniotes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513416DOI Listing
March 2021

Heating behavior using household air-conditioners during the COVID-19 lockdown in Wuhan: An exploratory and comparative study.

Build Environ 2021 May 23;195:107731. Epub 2021 Feb 23.

School of Civil Engineering, Chongqing University, Chongqing, 400044, PR China.

Wuhan is located in China's hot summer and cold winter (HSCW) zone, where the average temperature of the city from January to February 2020 is only 6.6 °C. This study aimed to explore and compare the air conditioner (AC) heating behavior of Wuhan residents before and after the COVID-19 lockdown. The date of commencement of the Wuhan lockdown (January 23, 2020) was considered the demarcation point to divide the AC monitoring data from the Internet of Things cloud platform into two groups; before and after Wuhan lockdown. Statistical methods were applied to analyze AC heating behavior of Wuhan residents from a total of 378 air conditioners during these two periods. The daily AC usage rate and average daily AC usage duration following the lockdown had a stronger correlation with daily outdoor temperature than that before the lockdown. AC heating behavior continued to demonstrate a part-time intermittent operation during the lockdown period, despite residents staying at home for a longer period. Trigger temperatures for occupants to turn on or adjust their AC during the lockdown period were overall 1-2 °C higher than before the lockdown. The AC heating demand in the HSCW zone has been increasing in recent years. These research results inform research on household energy demand and thermal comfort in China's HSCW zone, and provide a reference on the household behavioral changes in the occupants in the context of a lockdown as a result of the global COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.buildenv.2021.107731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900759PMC
May 2021

Unique flower-like Cur-metal complexes loaded liposomes for primary and metastatic breast cancer therapy.

Mater Sci Eng C Mater Biol Appl 2021 Feb 29;121:111835. Epub 2020 Dec 29.

Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China. Electronic address:

Mounting researches continue to support a favorable role for the drug metal complex against cancer progress and metastasis. However, pharmaceutical barriers were encountered when drug metal complexes needed further pre-clinical and clinical evaluations due to their poor aqueous solubility. In this research, liposomes loaded metal ion as nano-scaled reaction vehicles were used to carry out a synthesis reaction between metal ion and curcumin (Cur) to prepare Cur-metal drug liposomal formulations. The unique flower-like conformation of Cur-M liposomes was observed for the first time and dominated in the Cur-M liposomal formulations system by the cryo-transmission electron microscopy. Different metal ions behaved significant differences in formulations' appearance, release profile, cytotoxic effect against various cell lines, pharmacokinetic profiles, biodistribution and antitumor efficiency. Cur-M liposomes presented enhanced cellular uptake and ROS generation effects, thus augmenting the cytotoxicity of Cur. Superior performances of Cur-copper complexes liposomes were observed in improving Cur stability, promoting apoptosis, inhibiting the proliferation and angiogenesis, therefore enhancing therapeutic effect for primary and metastatic breast cancer. Overall, the current work highlights the potentially significant development value of Cur-M liposomes as an injectable agent for cancer treatment, even superior to the commercial agent Doxil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2020.111835DOI Listing
February 2021

A facile and universal method to achieve liposomal remote loading of non-ionizable drugs with outstanding safety profiles and therapeutic effect.

Acta Pharm Sin B 2021 Jan 13;11(1):258-270. Epub 2020 Aug 13.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apsb.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838024PMC
January 2021

Identification of estrogen receptor target genes involved in gonadal feminization caused by estrogen in Xenopus laevis.

Aquat Toxicol 2021 Jan 21;232:105760. Epub 2021 Jan 21.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Estrogens and estrogenic endocrine disrupting chemicals can cause gonadal feminization in some vertebrates mainly through estrogen receptor (ER), but the underlying molecular mechanisms are unclear. The present study aimed to identify ER target genes involved in estrogen-caused gonadal feminization in Xenopus laevis. Based on our recent transcriptomic data that 10 nM 17β-estradiol (E2) altered gene transcription in feminizing gonads of male X. laevis at NF stages 48, 50, and 52, we searched estrogen response element (ERE) using the Dragon ERE Finder software in the promoter region of all the E2-regulated genes. As a result, 163 genes containing ERE sequence were identified as predicted ER target genes at NF stage 50 (on the 14th day postfertilization), a crucial stage for gonadal feminization. Then, some of these predicted ER target genes were further investigated, mainly including the genes that were suggested to be involved in E2-caused gonadal feminization and genes being dramatically up or down-regulated by E2. Fifteen genes were demonstrated to be responsive to E2, in turn ER antagonist blocked the E2-regulated transcription. Finally, we identified 10 genes that can bind to ERα by a chromatin immunoprecipitation-qPCR. Taken together, we identified the 10 genes that contain predicted ERE sequences, are responsive to estrogen and ER antagonist, and have ability to bind to ER as ER target genes, including pglyrp2, apoa1, fgb, tdo2, ca6, nags, cpb2, tmprss6, nudc, zwilch. Our results could help to improve the understanding of the molecular mechanisms for gonadal feminization caused by estrogenic endocrine disrupting chemicals in X. laevis, and even in other species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aquatox.2021.105760DOI Listing
January 2021

Polymorphisms in oxidative stress, metabolic detoxification, and immune function genes, maternal exposure to ambient air pollution, and risk of preterm birth in Taiyuan, China.

Environ Res 2021 03 24;194:110659. Epub 2020 Dec 24.

Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA; Section of Surgical Outcomes and Epidemiology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA. Electronic address:

Exposure to air pollutants may be associated with preterm birth (PB) through oxidative stress, metabolic detoxification, and immune system processes. However, no study has investigated the interactive effects of maternal air pollution and genetic polymorphisms in these pathways on risk of PB. The study included 126 PB and 310 term births. A total of 177 single nucleotide polymorphisms (SNPs) in oxidative stress, immune function, and metabolic detoxification-related genes were examined and analyzed. The China air quality index (AQI) was used as an overall estimation of ambient air pollutants. Among 177 SNPs, four SNPs (GPX4-rs376102, GLRX-rs889224, VEGFA-rs3025039, and IL1A-rs3783550) were found to have significant interactions with AQI on the risk of PB (P were 0.001, 0.003, 0.03, and 0.04, respectively). After being stratified by the maternal genotypes in these four SNPs, 1.38 to 1.76 times of the risk of PB were observed as per interquartile range increase in maternal AQI among women who carried the GPX4-rs376102 AC/CC genotypes, the GLRX-rs889224 TT genotype, the VEGFA-rs3025039 CC genotype, or the IL1A-rs3783550 GT/TT genotypes. After adjustment for multiple comparisons, only GPX4-rs376102 and AQI interaction remained statistically significant (false discovery rate (FDR)=0.17). After additional stratification by preeclampsia (PE) status, a strongest association was observed in women who carried the GPX4-rs376102 AC/CC genotypes (OR, 2.26; 95% CI, 1.41-3.65, P=0.0002, FDR=0.035) in the PE group. Our study provided the first evidence that association between maternal air pollution and PB risk may be modified by the genetic polymorphisms in oxidative stress and immune function genes. Future large studies are necessary to replicate and confirm the observed associations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2020.110659DOI Listing
March 2021

CRISPR/Cas9 induces exon skipping that facilitates development of fragrant rice.

Plant Biotechnol J 2021 04 8;19(4):642-644. Epub 2020 Dec 8.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pbi.13514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051596PMC
April 2021

Remote loading paclitaxel-doxorubicin prodrug into liposomes for cancer combination therapy.

Acta Pharm Sin B 2020 Sep 26;10(9):1730-1740. Epub 2020 Apr 26.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX--DOX (PSD). The prodrug displayed comparable cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apsb.2020.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564015PMC
September 2020

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro-inflammatory responses in rats.

J Sci Food Agric 2021 Mar 17;101(4):1598-1608. Epub 2020 Sep 17.

Faculty of Thai Traditional Medicine, Prince of Songkla University, Hat Yai, Thailand.

Background: Literature has demonstrated that diabetes is associated with renal complication and testicular dysfunctions. The current study explored the potential of Tiliacora triandra extract and its major component against diabetic kidney and testicular damages in rats.

Methods: Diabetes was induced by high fat diet/streptozotocin (HFD/STZ) and treated orally with Tiliacora triandra extract (TTE, 100 and 400 mg kg body weight) and its major component, 5,7-dihydroxy-6-oxoheptadecanoic acid (DHA, 25 mg kg body weight) for 30 consecutive days. Testicular activities of testicular enzymes, serum levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), sperm parameters and urinalysis for protein and albumin levels were evaluated. Renal and testicular biomarkers of oxidative stress and pro-inflammation were analysed along with histology.

Results: The experimental diabetes induced significant alterations in the levels and activities of indices evaluated compared to non-diabetic normal rats. The 28-day treatment of diabetic rats with TTE and DHA markedly improved activities of testicular enzymes, restored levels of testosterone, LH and FSH and sperm parameters compared to untreated diabetic rats. TTE and DHA abrogated proteinuria and reversed urine albumin level. Testicular and renal oxidative stress and pro-inflammation were attenuated in diabetic rats treated with TTE and DHA. The diabetes-mediated histopathological damage was alleviated in the kidney and testis.

Conclusion: The protective effect of TTE and DHA against diabetes induced kidney and testicular damages may be related to its antioxidant and anti-inflammatory activities. © 2020 Society of Chemical Industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jsfa.10779DOI Listing
March 2021

Development and validation of a preoperative noninvasive predictive model based on circular tumor DNA for lymph node metastasis in resectable non-small cell lung cancer.

Transl Lung Cancer Res 2020 Jun;9(3):722-730

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Background: Clinical lymph node staging in resectable non-small cell lung cancer (NSCLC) patients not only indicates prognosis, but also determines primary treatment strategy. The demand of noninvasive tool for preoperative lymph node metastasis prediction remains significant. This study aimed to develop and externally validate a preoperative noninvasive predictive model based on circular tumor DNA (ctDNA) for the lymph node metastasis in resectable NSCLC patients.

Methods: Resectable NSCLC patients in TRACERx cohort were included as training group. Potential preoperative noninvasively accessible predictors were incorporated into the development of a nomogram via multivariate logistic regression. The predictive model was externally validated by a similar cohort from our hospital.

Results: Overall, 58 patients from TRACERx cohort were included as training group and 37 patients from our hospital were included as external validation group. Variant allele frequency (VAF) level of ctDNA was significantly associated with lymph node metastasis (OR: 4.89, 95% CI: 1.22-19.54, P=0.03). The predictive model incorporating age, tumor size and VAF demonstrated satisfactory discrimination and calibration in both training group (AUC =0.77, 95% CI: 0.65-0.90, P=0.001) and external validation group (AUC =0.84, 95% CI: 0.70-0.99, P=0.005).

Conclusions: High VAF level in preoperative ctDNA may indicate lymph node metastasis of resectable NSCLC. And a preoperative noninvasive predictive model based on ctDNA for the lymph node metastasis in resectable NSCLC patients was developed and externally validated with satisfactory discrimination and calibration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tlcr-20-593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354122PMC
June 2020

Transcriptomic analysis identifies early cellular and molecular events by which estrogen disrupts testis differentiation and causes feminization in Xenopus laevis.

Aquat Toxicol 2020 Sep 30;226:105557. Epub 2020 Jun 30.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Extensive studies have shown that estrogenic endocrine-disrupting chemicals (EDCs) can disrupt testis differentiation and even cause feminization in vertebrates. However, little is known about the mechanisms by which estrogenic EDCs disrupt testis differentiation. Here, we employed Xenopus laevis, a model amphibian species sensitive to estrogenic EDCs, to explore the molecular and cellular events by which 17β-estradiol (E2) disrupts testis differentiation and causes feminization. Following waterborne exposure to E2 from stage 45/46, genetically male X. laevis were confirmed to undergo testis differentiation inhibition and ovary differentiation activation at stages 52 and 53, ultimately displaying gonadal feminization at stage 66. Using a time-course RNA sequencing approach, we then identified thousands of differentially expressed transcripts (DETs) in genetically male gonad-mesonephros complexes at stages 48, 50 and 52 (the window for testis differentiation) between E2 treatment and the control. Enrichment analysis suggests alterations in cell proliferation, extracellular matrix, and cell motility following E2 exposure. Further verification by multiple methods demonstrated that E2 inhibited cell proliferation, disrupted extracellular matrix, and altered cell motility in the genetically male gonads compared with controls, implying that these events together contributed to testis differentiation disruptions and feminization in X. laevis. This study for the first time uncovered some of the early molecular and cellular events by which estrogen disrupts testicular differentiation and causes feminization in X. laevis. These new findings improve our understanding of the mechanisms by which estrogenic EDCs disrupt testicular differentiation in vertebrates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aquatox.2020.105557DOI Listing
September 2020

Targeting anti-cancer agents to bone using bisphosphonates.

Bone 2020 09 23;138:115492. Epub 2020 Jun 23.

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address:

The skeleton is affected by numerous primary and metastatic solid and hematopoietic malignant tumors, which can cause localized sites of osteolysis or osteosclerosis that can weaken bones and increase the risk of fractures in affected patients. Chemotherapeutic drugs can eliminate some tumors in bones or reduce their volume and skeletal-related events, but adverse effects on non-target organs can significantly limit the amount of drug that can be administered to patients. In these circumstances, it may be impossible to deliver therapeutic drug concentrations to tumor sites in bones. One attractive mechanism to approach this challenge is to conjugate drugs to bisphosphonates, which can target them to bone where they can be released at diseased sites. Multiple attempts have been made to do this since the 1990s with limited degrees of success. Here, we review the results of pre-clinical and clinical studies made to target FDA-approved drugs and other antineoplastic small molecules to bone to treat diseases affecting the skeleton, including osteoporosis, metastatic bone disease, multiple myeloma and osteosarcoma. Results to date are encouraging and indicate that drug efficacy can be increased and side effects reduced using these approaches. Despite these successes, challenges remain: no drugs have gone beyond small phase 2 clinical trials, and major pharmaceutical companies have shown little interest in the approach to repurpose any of their drugs or to embrace the technology. Nevertheless, interest shown by smaller biotechnology companies in the technology suggests that bone-targeting of drugs with bisphosphonates has a viable future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2020.115492DOI Listing
September 2020

Treatment of tubal heterotopic pregnancy with viable intrauterine pregnancy: Analysis of 81 cases from one tertiary care center.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 8;252:56-61. Epub 2020 Jun 8.

Department of Gynecology and Obstetrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, Guangzhou, 510080, PR China. Electronic address:

Objectives: The aim of our study was to analyze the treatment and pregnancy outcome of tubal heterotopic pregnancy (HP) patients with a viable intrauterine pregnancy (IUP) in our center.

Study Design: This was a retrospective analysis of 81 patients with tubal HP and a viable IUP. Patients were divided into either an expectant treatment group (29 patients) or a surgical treatment group (52 patients, 36 laparoscopy and 16 laparotomy). Data related to the basal clinical characteristic of all patients, rescue treatment and ectopic pregnancy (EP) rupture rate in the expectant treatment group, operation details in the surgical treatment group and pregnancy outcomes were collected and analyzed. Subgroup analyses were also performed.

Results: In the expectant treatment group, the abortion rate, EP rupture rate and rescue treatment rate were 10.34 % (3/29), 21.14 % (7/29) and 34.48 % (10/29), respectively; subgroup analysis revealed that the rescue treatment rate in patients with EP mass enlargement ≥50 % was 71.43 % (5/7), which was significantly higher than that in patients with EP mass enlargement <50 % (15.00 %, 3/20), with P = 0.011. In the surgical treatment group, the abortion rate of all patients was 15.38 % (8/52); the abortion rate was 22.22 % (8/36) in the laparoscopy subgroup, which was significantly higher than that in the laparotomy subgroup (0.00 %, 0/16), with P = 0.038.

Conclusions: Surgical treatment is a safe treatment option for tubal HP with a viable IUP, and laparoscopic surgery may be a potential risk factor for abortion. A high risk of failure exists for expectant management of tubal HP with a viable IUP, and EP mass enlargement ≥50 % may be a potential predictor of rescue treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.06.005DOI Listing
September 2020

Chemical Knockdown of MicroRNA with Small-Molecule Chimeras.

Chembiochem 2020 11 7;21(22):3180-3185. Epub 2020 Jul 7.

State Key Laboratory of Analytical Chemistry for Life Sciences Jiangsu Key Laboratory of Advanced Organic Materials School of Chemistry and Chemical Engineering Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, 210023, China.

This concept article introduces the emerging area of small-molecule chimeras (SMCs) for knocking down microRNAs (miRNAs), which are endogenous gene silencers involved in diverse pathological processes. Compared with agents for genetic knockdown, small-molecules hold significant promise in this field due to their ideal pharmacokinetic and pharmacodynamic properties. The SMCs introduced here are hetero-bifunctional molecules comprising small-molecule binders (SMBs) of miRNAs and chemical functionalities that either directly cleave RNAs or recruit ribonucleases to destroy RNAs. Binding of SMBs to miRNAs brings SMCs' chemical functionalities close to the miRNA, eventually causing miRNA degradation. Compared with parent SMBs, SMCs exhibit remarkably enhanced potency and specificity in miRNA inhibition. The development and application of SMCs for miRNAs will be discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbic.202000287DOI Listing
November 2020

Multidisciplinary treatment of abdominal wall endometriosis: A case report and literature review.

Eur J Obstet Gynecol Reprod Biol 2020 Jul 21;250:9-16. Epub 2020 Apr 21.

Department of Gynecology and Obstetrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, PR China. Electronic address:

A 31-year-old female patient presented with complaints of cyclic low abdominal wall pain and palpable abdominal mass for more than 4 years. Physical examination revealed a painful mass measuring 7 cm × 5 cm within the abdominal wall. Her surgical history included surgery for congenital lymphatic haemangioma twice and caesarean section delivery twice. Results of abdominal wall ultrasonography, magnetic resonance imaging, and enhanced computed tomography revealed a soft tissue mass within the abdominal wall, indicating abdominal wall endometriosis. Pathologic examination with fine-needle aspiration of the abdominal wall mass showed endometrial glands and stroma. A multidisciplinary treatment team was established at admission, and surgical excision of the abdominal wall endometriosis mass was recommended. Surgery was performed by our multidisciplinary treatment team. Intraoperatively, the abdominal wall muscle, symphysis pubis, and anterior bladder wall were found to be infiltrated by abdominal wall endometriosis tissue. The abdominal wall endometriosis mass was completely resected with part of the bladder wall, symphysis pubis periosteum, and abdominal wall muscle and fascia (measuring 9 cm × 8 cm × 6 cm). The abdominal wall defect could not be sutured in a routine manner; thus, autologous reconstruction of the abdominal wall defect with left anterolateral thigh musculocutaneous flap was performed. The patient recovered without complications, and follow-up was uneventful. The successful treatment in our case suggests that adequate preoperative examinations and multidisciplinary treatment team collaboration are crucial to the treatment of patients with large abdominal wall endometriosis mass. Anterolateral thigh musculocutaneous flap reconstruction may serve as an optional treatment for abdominal wall defects during surgical excision of abdominal wall endometriosis mass.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.04.046DOI Listing
July 2020

Transcriptional changes caused by estrogenic endocrine disrupting chemicals in gonad-mesonephros complexes of genetic male Xenopus laevis: Multiple biomarkers for early detection of testis differentiation disruption.

Sci Total Environ 2020 Jul 8;726:138522. Epub 2020 Apr 8.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Our recent study revealed some early molecular and cellular events in which 17β-estradiol (E2) disrupted testis differentiation and resulted in feminization in Xenopus laevis (the African clawed frog), an ideal species for studying reproductive endocrine disruption by estrogenic endocrine disrupting chemicals (EDCs). On this basis, we aimed to develop multiple biomarkers for early detection of testis differentiation disruption by estrogenic EDCs in X. laevis. Tadpoles at stage 45/46 were exposed to four known estrogenic EDCs with different estrogenic activities, including E2, diethylstilbestrol (DES), mestranol (MES) and 4-n-nonyphenol (NP). At stage 53, gonadal morphological and histological changes as well as altered sex-dimorphic gene expression in gonad-mesonephros complexes (GMCs) showed that these estrogenic EDCs disrupted testis differentiation and caused feminization to different degrees. Then we measured transcriptional changes of 48 candidate genes, which are believed to be associated with E2-induced testis differentiation alterations, in GMCs at stage 50. As a result, 19 genes were found to be transcriptionally altered by all test chemicals and proposed as promising biomarkers for early detection of testis differentiation disruption by estrogenic EDCs. Finally, all biomarker responses were integrated as integrated biomarker response (IBR) index to characterize testis differentiation disruption by these estrogenic EDCs in X. laevis. Compared with the methods used in previous studies, the multiple biomarker test using X. laevis at early developmental stages largely shortens the exposure duration, thereby achieving the goal of rapid detection. Certainly, the biomarker test needs further validations in the future study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.138522DOI Listing
July 2020

The IAP Antagonist SM-164 Eliminates Triple-Negative Breast Cancer Metastasis to Bone and Lung in Mice.

Sci Rep 2020 04 24;10(1):7004. Epub 2020 Apr 24.

Department of Pathology and Laboratory Medicine, and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.

The most challenging issue for breast cancer (BC) patients is metastasis to other organs because current therapies do not prevent or eliminate metastatic BC. Here, we show that SM-164, a small molecule inhibitor, which degrades inhibitor of apoptosis proteins (IAPs), eliminated early-stage metastases and reduced progression of advanced BC metastasis from MDA-MB-231 BC cells in bones and lungs of nude mice. Mechanistically, SM-164-induced BC cell death is TNFα-dependent, with TNFα produced by IL-4-polarized macrophages triggering MDA-MB-231 cell apoptosis in combination with SM-164. SM-164 also inhibited expression of RANKL, which mediates interactions between metastatic BC and host microenvironment cells and induces osteoclast-mediated osteolysis. SM-164 did not kill adriamycin-resistant BC cells, while adriamycin inhibited SM-164-resistant BC cell growth, similar to parental cells. We conclude that SM-164 is a promising therapeutic agent for early stage bone and lung metastasis from triple-negative breast cancer that should be given prior to conventional chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-64018-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181667PMC
April 2020
-->