Publications by authors named "Bo Lv"

187 Publications

Exosomal LncRNA RP5-977B1 as a novel minimally invasive biomarker for diagnosis and prognosis in non-small cell lung cancer.

Int J Clin Oncol 2022 Jun 28;27(6):1013-1024. Epub 2022 Apr 28.

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhouda Road, Guangzhou, 510515, Guangdong, China.

Background: Lung cancer is the leading cause of cancer-related deaths in the world. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. For lack of conveniently sensitive and specific biomarkers, the majority of patients are in the late stage at initial diagnosis. Long non-coding RNAs (LncRNAs), a novel type of non-coding RNA, have recently been recognized as critical factors in tumor initiation and progression, but the role of exosomal LncRNAs has not been thoroughly excavated in NSCLC yet.

Methods: We isolated exosomes from the serum of patients with NSCLC and healthy controls. Exosome RNA deep sequencing was subsequently performed to detect differentially expressed exosomal LncRNAs. qRT-PCR assay was then utilized to validate dysregulated LncRNAs in both testing and multicentric validation cohort. Receiver operating characteristic (ROC) curve was used to detect the diagnostic capability of exosomal biomarkers. Furthermore, Kaplan-Meier analysis was applied to evaluate the prognostic values of these molecules.

Results: On the basis of analysis, we found that novel exosomal LncRNA RP5-977B1 exhibited higher levels in NSCLC than that in the healthy controls. The area under the curve (AUC) value of exosomal RP5-977B1 was 0.8899 and superior to conventional biomarkers CEA and CYFRA21-1 both in testing and multicentric validation cohort. Interestingly, the diagnostic capability of exosomal RP5-977B1 was also validated in early-stage patients with NSCLC. Furthermore, high expression of exosomal RP5-977B1was closely related with worse prognosis in NSCLC (P = 0.036).

Conclusions: Our results suggested that exosomal RP5-977B1 might serve as a novel "liquid biopsy" diagnostic and prognostic biomarker to monitor NSCLC and improve possible therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-022-02129-5DOI Listing
June 2022

Dosimetric Study of Deep Learning-Guided ITV Prediction in Cone-beam CT for Lung Stereotactic Body Radiotherapy.

Front Public Health 2022 22;10:860135. Epub 2022 Mar 22.

Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai, China.

Purpose: The purpose of this study was to evaluate the accuracy of a lung stereotactic body radiotherapy (SBRT) treatment plan with the target of a newly predicted internal target volume (ITV) and the feasibility of its clinical application. ITV was automatically generated by our in-house deep learning model according to the cone-beam CT (CBCT) image database.

Method: A retrospective study of 45 patients who underwent SBRT was involved, and Mask R-CNN based algorithm model helped to predict the internal target volume (ITV) using the CBCT image database. The geometric accuracy of ITV was verified by the Dice Similarity Coefficient (DSC), 3D Motion Range (R), Relative Volume Index (RVI), and Hausdorff Distance (HD). The PTV was generated by ITV, which was registered and then projected on free-breath CT (FBCT) images. The PTV was margined from the GTV on FBCT images gross tumor volume on free-breath CT (GTV). Treatment plans with the target of Predict planning target volume on CBCT images (PTV) and planning target volume on free-breath CT (PTV) were respectively re-established, and the dosimetric parameters included the ratio of the volume of patients receiving at least the prescribed dose to the volume of PTV (R), the ratio of the volume of patients receiving at least 50% of the prescribed dose to the volume of PTV in the Radiation Therapy Oncology Group (RTOG) 0813 Trial (R), Gradient Index (GI), and the maximum dose 2 cm from the PTV (D), which were evaluated Plan, plan which based on PTV (Plan), and plan which based on PTV (Plan).

Result: The geometric results showed that there existed a good correlation between ITV and ITV on the 4-dimensional CT [ITV; DSC= 0.83 ±0.18]. However, the average volume of ITV was 10% less than that of ITV ( = 0.333). No significant difference in dose coverage was found in V for the ITV with 99.98 ± 0.04% in the ITV vs. 97.56 ± 4.71% in the ITV ( = 0.162). Dosimetry parameters of PTV, including R, R, GI and D showed no statistically significant difference between each plan ( > 0.05).

Conclusion: Dosimetric parameters of Plan are clinically comparable to those of the original Plan This study confirmed that the treatment plan based on ITV produced by our model could automatically meet clinical requirements. Thus, for patients undergoing lung SBRT, the model has great potential for using CBCT images for ITV contouring which can be used in treatment planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2022.860135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980420PMC
April 2022

OsHYPK-mediated protein N-terminal acetylation coordinates plant development and abiotic stress responses in rice.

Mol Plant 2022 Apr;15(4):740-754

Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agriculture University, Taian, Shandong 271018, China. Electronic address:

N-terminal acetylation is one of the most common protein modifications in eukaryotes, and approximately 40% of human and plant proteomes are acetylated by ribosome-associated N-terminal acetyltransferase A (NatA) in a co-translational manner. However, the in vivo regulatory mechanism of NatA and the global impact of NatA-mediated N-terminal acetylation on protein fate remain unclear. Here, we identify Huntingtin Yeast partner K (HYPK), an evolutionarily conserved chaperone-like protein, as a positive regulator of NatA activity in rice. We found that loss of OsHYPK function leads to developmental defects in rice plant architecture but increased resistance to abiotic stresses, attributable to perturbation of the N-terminal acetylome and accelerated global protein turnover. Furthermore, we demonstrated that OsHYPK is also a substrate of NatA and that N-terminal acetylation of OsHYPK promotes its own degradation, probably through the Ac/N-degron pathway, which could be induced by abiotic stresses. Taken together, our findings suggest that the OsHYPK-NatA complex plays a critical role in coordinating plant development and stress responses by dynamically regulating NatA-mediated N-terminal acetylation and global protein turnover, which are essential for maintaining adaptive phenotypic plasticity in rice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molp.2022.03.001DOI Listing
April 2022

Integrated transcriptomics and proteomics provide new insights into the cadmium-induced ovarian toxicity on Pardosa pseudoannulata.

Chemosphere 2022 Jun 9;297:134255. Epub 2022 Mar 9.

Division of Plant Science and Technology, University of Missouri, Columbia, MO, 65211, USA.

Cadmium (Cd) pollution is intractable heavy metal pollution in the farmland ecosystem, posing a life-threatening challenge to the paddy field organisms. Spiders are riveting animal biomarkers for evaluating Cd-induced toxicity, yet the effects of long-term Cd toxicity on spider reproductive function and its underlying mechanism remain unclear. In the present study, we found that Cd exposure impaired the antioxidant enzyme system in the wolf spider Pardosa pseudoannulata and decreased the concentration of four antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase, and peroxidase) (p < 0.05). The content of vitellogenin and the number of hatched spiderlings were also dramatically reduced under Cd stress (p < 0.05), indicating that Cd stress could vitiate the fecundity of P. pseudoannulata. Moreover, a total of 10,511 differentially expressed genes (DEGs) and 391 proteins (DEPs) were yielded from the ovarian transcriptome and proteome, and a mass of genes and proteins involved in protein processing in endoplasmic reticulum (ER) were significantly down-regulated. DEGs and DEPs directly encoding the antioxidant enzyme system and/or vitellogenesis were also distinctively down-regulated. In addition, we illustrated that the PI3K-AKT signaling pathway might play a crucial role in regulating protein synthesis, cell cycle, growth, differentiation and survival in P. pseudoannulata. The effects of protein processing in ER and PI3K-AKT pathways could further trigger transcriptional factor Forkhead shackling the protein synthesis and cell growth process. Collectively, this integrated analysis identified the Cd-induced reproductive toxicity on P. pseudoannulata and provided multifaceted insights to investigate the molecular mechanisms of spiders to Cd pollution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2022.134255DOI Listing
June 2022

Comparative analysis unveils the cadmium-induced reproductive toxicity on the testes of Pardosa pseudoannulata.

Sci Total Environ 2022 Jul 4;828:154328. Epub 2022 Mar 4.

Division of Plant Sciences and Technology, University of Missouri, Columbia, MO 65211, USA.

Cadmium (Cd) pollution is one of the most serious heavy metal pollutions in the world, which has been demonstrated to cause different toxicities to living organisms. Cd has been widely suggested to cause reproductive toxicity to vertebrates, yet its reproductive toxicity to invertebrates is not comprehensive. In this study, the wolf spider Pardosa pseudoannulata was used as a bioindicator to evaluate the male reproductive toxicity of invertebrates under Cd stress. Cd stress had no effect on the color, size and length of testis. However, Cd significantly increased the contents of catalase, glutathione peroxidase and malondialdehyde, the antioxidants in the testis of P. pseudoannulata. Then we analyzed the transcriptome of testis exposed to Cd, and identified a total of 4739 differentially expressed genes (DEGs) compared to control, with 2368 up-regulated and 2371 down-regulated. The enrichment analysis showed that Cd stress could affect spermatogenesis, sperm motility, post-embryonic development, oxidative phosphorylation and metabolism and synthesis of male reproductive components. At the same time, the protein-protein interaction network was constructed with the generated DEGs. Combined with the enrichment analysis of key modules, it revealed that Cd stress could further affect the metabolic process in testis. In general, the analysis of testicular damage and transcriptome under Cd stress can provide a novel insight into the reproductive toxicity of Cd on rice filed arthropods and offer a reference for the protection of rice filed spiders under Cd pollution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2022.154328DOI Listing
July 2022

Versatile polarization manipulation in vanadium dioxide-integrated terahertz metamaterial.

Opt Express 2022 Feb;30(4):5439-5449

Broadband and switchable versatile polarization metamaterial is crucial in the applications of imaging, sensing and communication, especially in the terahertz frequency. Here, we investigated versatile polarization manipulation in a hybrid terahertz metamaterial with bilayer rectangular rods and a complementary vanadium dioxide (VO) layer. The VO phase transition enables a flexible switching from dual-band asymmetric transmission to dual-band reflective half-wave plate. The full width half maximum (FWHM) bandwidths of dual-band asymmetric transmission are 0.77 and 0.21 THz, respectively. The polarization conversion ratio (PCR) of the reflective metamaterial is over 0.9 in the frequency ranges of 1.01-1.17 THz and 1.47-1.95 THz. Angular dependences of multiple polarization properties are studied. The proposed switchable polarization metamaterial is important to the development of multifunctional polarization devices and multichannel polarization detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.447453DOI Listing
February 2022

Highly sensitive gas sensor based on a parity-time-symmetric system.

J Opt Soc Am A Opt Image Sci Vis 2022 Feb;39(2):227-232

Achieving extremely high sensitivity is an important indicator in the development of novel and stable gas concentration sensors. In this paper, we present a gas concentration sensor with parity-time symmetry for high sensitivity at low concentrations. The proposed sensor can detect toxic gases, such as benzene, bromine, and acetone, by probing the faint changing of the permittivity. Furthermore, the level of the sensitivity can be adjusted by the resistance segment, which is realized by various metallic formations. Our proposed structure provides a novel idea for the development of future gas concentration sensors, showing an exciting prospect for gas sensing technologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/JOSAA.443024DOI Listing
February 2022

A Traditional Chinese Medicine for the Treatment of Endometrial Hyperplasia via Regulating the HPO Axis in Rats.

Evid Based Complement Alternat Med 2022 2;2022:5200608. Epub 2022 Feb 2.

Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha 410081, China.

Dysfunctional uterine bleeding, accompanied by endometrial hyperplasia (EH), is a common gynecological disease that seriously affects female physical and mental health. Some drugs have been prompted to cure the disease, but most medications have certain side effects and limitations. In the present study, we demonstrated an unexploited Chinese traditional medicine, a combination of , , and (SCS), which could be used for the treatment of EH and associated complications in rats. We identified the active components from the three Chinese herbs via thin-layer chromatography and high-performance liquid chromatography methods. In addition, serum biochemical indexes and histologic section results found that acute high-dose SCS exerted no adverse impacts on the rats. We then showed that SCS shortened coagulation time (=0.018) and degree of swelling (=0.021) on rats at 30 min compared to blank control. Further studies proved that recovered endometrial thickness was associated with the modulation of four hormones (follicle-stimulating hormone, luteinizing hormone, estrogen, and progesterone). Specifically, follicle-stimulating hormone and progesterone contents increased gradually with time, and estrogen was decreased, whereas luteinizing hormone content was returned to normal after a short-term elevation ( < 0.05). Besides, SCS increased uterine endometrium's mRNA expression levels of matrix metalloproteinase-1 ( < 0.001) and tissue inhibitor of matrix metalloproteinase-1 ( < 0.001), promoting the repair of proliferating endometrium in the rats. Collectively, our study indicates that SCS harbors a profoundly curative effect on the treatment of EH and relative complications and uncovers the mechanism at molecular and gene expression levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/5200608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828340PMC
February 2022

High efficient production of plant flavonoids by microbial cell factories: Challenges and opportunities.

Metab Eng 2022 03 25;70:143-154. Epub 2022 Jan 25.

Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, 832003, PR China; Key Lab for Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Tsinghua University, Beijing, 100084, PR China; Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, PR China. Electronic address:

Plant flavonoids are secondary metabolites containing a benzo-γ-pyrone structure, which are widely present in plants and have a variety of physiological and pharmacological activities. However, current flavonoid production from plant extraction or chemical synthesis does not meet the requirements of green and sustainable development. Fortunately, microbial synthesis of flavonoids has shown the potential for large-scale production with the advantages of being controllable and environmentally friendly, and a variety of microorganisms have been developed as microbial cell factories (MCFs) to synthesize plant flavonoids owing to the feasibility of genetic manipulations. However, most of MCFs have not yet been commercialized and industrialized because of the challenges posed by unbalanced metabolic flux among various pathways and conflict between cell growth and production. Here, strategies for coping with the challenges are summarized in terms of enzymes, pathways, metabolic networks, host cells. And combined with protein structure prediction, de novo protein design, artificial intelligence (AI), biocatalytic retrosynthesis, and intelligent stress resistance, it provides new insights for the high efficient production of plant flavonoids and other plant natural products in MCFs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymben.2022.01.011DOI Listing
March 2022

CircFOXP1: A novel serum diagnostic biomarker for non-small cell lung cancer.

Int J Biol Markers 2022 Mar 24;37(1):58-65. Epub 2022 Jan 24.

Department of Laboratory Medicine, 74669Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.

Background: Emerging evidence suggests that circular RNAs (circRNAs) were aberrantly expressed in the patients of non-small cell lung cancer (NSCLC). This study aims to evaluate the diagnostic value of potential serum biomarker in circRNAs.

Methods: Serum circRNAs were extracted and purified by RNA isolated kit and identified by quantitative real time-polymerase chain reaction (qRT-PCR) assay. We then performed a receiver operating characteristic (ROC) curve to estimate the diagnostic efficacy. The relationship between circRNA and clinic characteristics of patients was analyzed by SPSS 25.0. Univariate and multivariate analyses were also used to evaluate its diagnostic capability. The mechanism of circFOXP1 was further excavated by bioinformatics analysis.

Results: By performing qRT-PCR assay, we identified that circFOXP1 (hsa_circ_0008234) and conventional tumor markers (carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA21-1)) were all significantly overexpressed in the serum of patients with NSCLC when compared with healthy controls ( < 0.05). While the ROC curves analysis demonstrated that area under the curve of circFOXP1 was obviously superior to CEA and CYFRA21-1, which exerted more diagnostic advantage. Univariate and multivariate analyses revealed that serum circFOXP1 was an independent diagnostic molecule, and was significantly correlated with T stage and lymphatic metastasis in NSCLC ( < 0.05). Mechanistically, circFOXP1 might target hsa-miR-370-3p and hsa-miR-18a-5p, and be involved in vascular endothelial growth factor signaling pathways to regulate proliferative and metastasis processes.

Conclusion: Our results highlight the preferable diagnostic potential of serum circFOXP1 in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/17246008211073151DOI Listing
March 2022

LncRNA ubiquitin-binding protein domain protein 10 antisense RNA 1 inhibits colon adenocarcinoma progression via the miR-515-5p/slit guidance ligand 3 axis.

Bioengineered 2022 02;13(2):2308-2320

Department of General Surgery, Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China.

Dysregulated long non-coding RNAs (lncRNAs) play an important role in cancer progression. However, there have been limited reports to date of the involvement of ubiquitin-binding protein domain protein 10 antisense RNA 1 (UBXN10-AS1) in cancer. Our aim was to explore the role and underlying mechanism of UBXN10-AS1 in the occurrence of colon adenocarcinoma (COAD). Real-time quantitative PCR and Western blotting were performed to determine the expression of UBXN10-AS1, miR-515-5p, and Slit guidance ligand 3 (SLIT3). Cell Counting Kit-8 and wound healing scratch assays were performed to measure COAD cell proliferation and migration. A xenograft assay was performed to examine tumor growth in vivo. Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to determine the binding interaction among miR-515-5p, UBXN10-AS1, and SLIT3. The results showed that UBXN10-AS1 and SLIT3 were expressed at low levels in COAD tissues, while miR-515-5p was expressed at high levels. UBXN10-AS1 overexpression suppressed tumor growth in vitro and in vivo. The luciferase reporter and RNA RIP assays demonstrated that UBXN10-AS1 targeted miR-515-5p, which in turn targeted SLIT3. Functionally, miR-515-5p overexpression reversed the inhibition of COAD cell proliferation and migration by UBXN10-AS1 overexpression, and SLIT3 overexpression counteracted the oncogenicity of miR-515-5p. Our study shows that UBXN10-AS1 modulates the miR-515-5p/SLIT3 axis, thereby resulting in the inhibition of COAD cell proliferation and migration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21655979.2021.2024396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974015PMC
February 2022

Active beam manipulation and convolution operation in VO-integrated coding terahertz metasurfaces.

Opt Lett 2022 Jan;47(2):441-444

Coding metasurfaces have received tremendous interest due to their unprecedented control of beams through the flexible design of coding sequences. However, realizing tunable coding metasurfaces with scattering-pattern shifts in the terahertz range is still challenging. Here, we propose a VO-integrated coding metasurface to realize a thermally controlled scattering-pattern shift by convolution operation. The required phase profiles and high amplitudes of 1-bit and 2-bit coding metasurfaces are easily obtained only by changing the length of the VO cut-wires. The insulator-metal phase transition of the VO cut-wires leads to an ultrafast switching effect between multiple deflected scattering beams and one normally reflected beam. In particular, the VO phase transition contributes to dynamical convolution operations of the 2-bit coding metasurface. The proposed VO-integrated coding metasurfaces are important for realizing tunable terahertz beam manipulation as well as arbitrary required scattering beams.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.447377DOI Listing
January 2022

Comparative analysis of cadmium-induced toxicity and survival responses in the wolf spider Pirata subpiraticus under low-temperature treatment.

Environ Sci Pollut Res Int 2022 May 12;29(22):32832-32844. Epub 2022 Jan 12.

College of Life Science, Hunan Normal University, Changsha, 410081, China.

Cadmium (Cd) pollution is a serious heavy metal pollution in paddy fields, but its effect and underlying mechanism on soil arthropod overwintering and cold resistance are still unclear. In the present study, adult females of the wolf spider Pirata subpiraticus exposed to Cd stress underwent a simulated temperature process (25℃ → 16℃ → 8℃ → 4℃). The mortality rate and content of nutrients in the Cd-treated spiders were dramatically elevated after low-temperature treatment compared to those in the Cd-free control spiders under the same temperature condition. To uncover the putative modulatory mechanism of Cd on cold tolerance in P. subpiraticus, we employed an in-depth RNA sequencing analysis and yielded a total of 888 differentially expressed genes (DEGs). Besides, we characterized genes that participate in multiple cryoprotectant syntheses, including arginine, cysteine, glucose, glycerol, heat shock protein, and mannose. The enrichment analyses found that most of the DEGs involved in biological processes and pathways were related to carbohydrate, lipid, and protein metabolism. Notably, ten Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as starch and sucrose metabolism, arachidonic acid metabolism, amino acid metabolism, mineral absorption, and vitamin digestion and absorption, were distinctively enriched with downregulated genes. Meanwhile, we also identified that seven DEGs might inhibit the KEGG pathway of ovarian steroidogenesis and potentially cripple ovarian function and fecundity in the spider. The decreased egg sac weight, number of hatched spiderlings, and vitellin concentration further supported the view that Cd exposure vitiates the overwintering spider's fecundity. Collectively, the comparative analysis provides a novel perspective regarding the survival response and fecundity on the cold tolerance of spiders under Cd stress and offers a profound insight for evaluating Cd-induced toxicity on overwintering arthropods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-022-18548-wDOI Listing
May 2022

Development and Validation of a Nomogram Incorporating Colloid Osmotic Pressure for Predicting Mortality in Critically Ill Neurological Patients.

Front Med (Lausanne) 2021 24;8:765818. Epub 2021 Dec 24.

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

The plasma colloid osmotic pressure (COP) values for predicting mortality are not well-estimated. A user-friendly nomogram could predict mortality by incorporating clinical factors and scoring systems to facilitate physicians modify decision-making when caring for patients with serious neurological conditions. Patients were prospectively recruited from March 2017 to September 2018 from a tertiary hospital to establish the development cohort for the internal test of the nomogram, while patients recruited from October 2018 to June 2019 from another tertiary hospital prospectively constituted the validation cohort for the external validation of the nomogram. A multivariate logistic regression analysis was performed in the development cohort using a backward stepwise method to determine the best-fit model for the nomogram. The nomogram was subsequently validated in an independent external validation cohort for discrimination and calibration. A decision-curve analysis was also performed to evaluate the net benefit of the insertion decision using the nomogram. A total of 280 patients were enrolled in the development cohort, of whom 42 (15.0%) died, whereas 237 patients were enrolled in the validation cohort, of which 43 (18.1%) died. COP, neurological pathogenesis and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were predictors in the prediction nomogram. The derived cohort demonstrated good discriminative ability, and the area under the receiver operating characteristic curve (AUC) was 0.895 [95% confidence interval (CI), 0.840-0.951], showing good correction ability. The application of this nomogram to the validation cohort also provided good discrimination, with an AUC of 0.934 (95% CI, 0.892-0.976) and good calibration. The decision-curve analysis of this nomogram showed a better net benefit. A prediction nomogram incorporating COP, neurological pathogenesis and APACHE II score could be convenient in predicting mortality for critically ill neurological patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.765818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740271PMC
December 2021

Effect of Sperm Cryopreservation on miRNA Expression and Early Embryonic Development.

Front Cell Dev Biol 2021 22;9:749486. Epub 2021 Dec 22.

Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China.

Although sperm preservation is a common means of personal fertility preservation, its effects on embryonic development potential need further investigation. The purpose of this study was to identify key microRNA (miRNA) in cryopreserved sperm and determine the changes of these miRNAs and their target genes during embryonic development using cryopreserved sperm. Moreover, the embryonic development potential of cryopreserved sperm was estimated in assisted reproductive technology (ART), where key miRNAs and target genes were validated in sperm and subsequent embryos. Clinical data of embryonic development from cryopreserved sperm indicated a significant decrease in fertilization rate in both fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cases, as well as a reduction in blastocyst formation rate in ICSI cases. Meanwhile there was a significant increase in blocked embryo ratio of Day1, Day2, and Day3.5 embryos when frozen-thawed mouse sperm was used, compared with fresh mouse sperm, suggesting a potential negative effect of sperm cryopreservation on embryonic development. From frozen-thawed and fresh sperm in humans and mice, respectively, 21 and 95 differentially expressed miRNAs (DEmiRs) were detected. miR-148b-3p were downregulated in both human and mouse frozen-thawed sperm and were also decreased in embryos after fertilization using cryopreserved sperm. Target genes of miR-148b-3p, Pten, was identified in mouse embryos using quantitative real-time PCR (qRT-PCR) and Western blot (WB). In addition, common characters of cryopreservation of mouse oocytes compared with sperm were also detected; downregulation of miR-148b-3p was also confirmed in cryopreserved oocytes. In summary, our study suggested that cryopreservation of sperm could change the expression of miRNAs, especially the miR-148b-3p across humans and mice, and may further affect fertilization and embryo development by increasing the expression of Pten. Moreover, downregulation of miR-148b-3p induced by cryopreservation was conserved in mouse gametes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.749486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728010PMC
December 2021

The Changes of KCNQ5 Expression and Potassium Microenvironment in the Retina of Myopic Guinea Pigs.

Front Physiol 2021 23;12:790580. Epub 2021 Dec 23.

Department of Ophthalmology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

KCNQ5 is suggestively associated with myopia, but its specific role in the myopic process has not been studied further. The aim of this study was to investigate the expression of potassium channel gene KCNQ5 and the changes of K microenvironment within the retina of form deprivation myopia (FDM) guinea pigs. A total of 60 guinea pigs were randomly divided into the normal control (NC) group, the self-control (SC) group, and the form-deprivation (FD) group for different treatments. Molecular assays and immunohistochemistry (IHC) were conducted to measure the expression and distribution of KCNQ5-related gene and protein in the retina. We determined the K concentration in the retina. In addition, the possible effects of form deprivation on potassium ionic currents and the pharmacological sensitivity of KCNQ5 activator Retigabine and inhibitor XE991 to the M-current in RPE cells were investigated using the patch-clamp technique. As a result, FD eyes exhibited more myopic refraction and longer AL. The mRNA and protein levels of KCNQ5 significantly decreased in the FD eyes, but the K concentration increased. In addition, the M-type K current [IK] density decreased in FD RPE cells, and were activated or inhibited in a concentration-dependent manner due to the addition of Retigabine or XE991. Overall, KCNQ5 was significantly downregulated in the retina of FD guinea pigs, which may be associated with the increasing K concentration, decreasing IK density, and elongating ocular axis. It suggested that KCNQ5 may play a role in the process of myopia, and the intervention of potassium channels may contribute to the prevention and control of myopia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.790580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733613PMC
December 2021

Cardiac Dose Control and Optimization Strategy for Left Breast Cancer Radiotherapy With Non-Uniform VMAT Technology.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211053752

Huadong Hospital, 535038Fudan University, Shanghai, China.

A novel in-house technology "Non-Uniform VMAT (NU-VMAT)" was developed for automated cardiac dose reduction and treatment planning optimization in the left breast radiotherapy. The NU-VMAT model based on I (gantry MLC Movement coefficient index) was established to optimize the volumetric modulated arc therapy (VMAT) MLC movement and modulation intensity in certain gantry angles. The ESAPI embedded in Eclipse® was employed to connect TPS and the optimization program via I/O relevant DICOM RT files. The adjuvant whole-breast radiotherapy of 14 patients with left breast cancer was replanned using our NU-VMAT technology in comparison with VMAT and IMRT technology. Dosimetric parameters including D, D, and D of PTV, V, V, and V of ipisilateral lung, V, D, D, and D of heart, monitor units (MUs), and delivery time derived from IMRT, VMAT, and NU-VMAT plans were evaluated for plan quality and delivery efficiency. The quality assurance (QA) was conducted using both point-dose and planar-dose measurements for all treatment plans. The I curves with plan optimization (range from 50% to 147%) were converged more significantly than I- curves (range from 0% to 297%). The dose distribution requirements of the target and normal tissues could be met using IMRT, VMAT, or NU-VMAT; the lowest D was achieved in NU-VMAT plans (5.38 ± 0.46 Gy vs 5.63 ± 0.61 Gy in IMRT and 7.95 ± 0.52 Gy in VMAT plans). Statistically significant differences were found in terms of delivery time and MU when comparing IMRT with VMAT and NU-VMAT plans ( < .05). In comparison with IMRT plans, the MU and delivery time in NU-VMAT plans dramatically decreased by 69.8% and 28.4%, respectively. Moreover, NU-VMAT plans showed a high gamma passing rate (96.5% ± 1.11) in plane dose verification and minimal dose difference (2.4% ± 0.19) in point absolute dose verification. Our non-uniform VMAT facilitated the treatment strategy optimization for left breast cancer radiotherapy with dosimetric advantage in cardiac dose reduction and delivery efficiency in comparison with the conventional VMAT and IMRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/15330338211053752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606722PMC
March 2022

Separation and purification of plant terpenoids from biotransformation.

Eng Life Sci 2021 Nov 10;21(11):724-738. Epub 2021 Jun 10.

Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering Ministry of Industry and Information Technology Institute of Biochemical Engineering School of Chemistry and Chemical Engineering Beijing Institute of Technology Beijing P. R. China.

The production of plant terpenoids through biotransformation has undoubtedly become one of the research hotspots, and the continuous upgrading of the corresponding downstream technology is also particularly important. Downstream technology is the indispensable technical channel for the industrialization of plant terpenoids. How to efficiently separate high-purity products from complex microbial fermentation broths or enzyme-catalyzed reactions to achieve high separation rates, high returns and environmental friendliness has become the focus of research in recent years. This review mainly introduces the common separation methods of plant terpenoids based on biotransformation from the perspectives of engineering strain construction, unit separation technology, product properties and added value. Then, further attention was paid to the application prospects of intelligent cell factories and control in the separation of plant terpenoids. Finally, some current challenges and prospects are proposed, which provide possible directions and guidance for the separation and purification of terpenoids and even industrialization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/elsc.202100014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576074PMC
November 2021

A systematic review and meta-analysis of elastic stockings for prevention of thrombosis after orthopedic surgery.

Ann Palliat Med 2021 10;10(10):10467-10474

Department of Orthopedics, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu, China; University of Electronic Science and Technology of China, Chengdu, China.

Background: To investigate the preventive effect of elastic stockings on deep vein thrombosis (DVT) after orthopedic surgery by literature search and meta-analysis.

Methods: PubMed, Embase and Cochrane were selected as the search database platforms to search the literature of randomized controlled trials related to elastic stockings and DVT published from 2008 to date. Revman 5.3.5 software was used for statistical analysis of the data to obtain forest and funnel plots.

Results: In this study, 90 studies were initially screened and 7 were finally included, covering a total of 3,116 patients. Meta-analysis showed that the 7 studies had statistical heterogeneity (I2=32%, P=0.18), so a random effect model was used. The obtained statistic was [odds ratio (OR) =0.59, 95% confidence interval (CI): (0.34, 1.03)], the statistical effect size was Z=1.84, P=0.07, and the difference was not statistically significant, so a stepwise sensitivity analysis was performed by the exclusion method. One study was excluded, and the remaining 6 showed homogeneity (I2=0%, P=0.46). They were analyzed by subgroup according to the type of operation: ankle surgery or hip and knee arthroplasty. The internal literatures of each subgroup were homogeneous: ankle surgery subgroup (I2=0%, P=0.43), hip and knee arthroplasty subgroup (I2=0%, P=0.88). Therefore, fixed effect mode analysis was used, and the effect size of elastic stockings after ankle surgery was Z=3.65, P=0.0003, while the effect size of elastic stockings in the hip and knee arthroplasty subgroup was Z=1.23, P=0.22.

Discussion: Elastic stockings had an obvious preventive effect on DVT in patients undergoing ankle surgery, but not in patients undergoing lumbar, knee or spinal surgery. It is necessary to combine anticoagulant drugs and other physical therapies to prevent DVT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-21-2231DOI Listing
October 2021

Effects of bariatric surgery on the menstruation- and reproductive-related hormones of women with obesity without polycystic ovary syndrome: a systematic review and meta-analysis.

Surg Obes Relat Dis 2022 Jan 10;18(1):148-160. Epub 2021 Sep 10.

Department of Endocrinology, Shengjing Hospital, China Medical University, Shenyang, China. Electronic address:

Background: Bariatric surgery is an effective treatment for severe obesity. Several studies have been conducted on the effects of bariatric surgery on the reproductive function of women with obesity who do not have polycystic ovary syndrome (PCOS).

Objectives: To evaluate the effects of bariatric surgery on the menstruation and reproductive related hormones of women of childbearing age with who do not have PCOS.

Setting: A systematic review and meta-analysis at a university hospital.

Methods: Online databases were searched for all studies reporting the efficacy of bariatric surgery for women with obesity until March 2021. The language of publication was limited to English and Chinese. Incidence of abnormal menstruation and reproductive-related hormone levels were the primary outcomes.

Results: Fifteen studies comprising 725 patients were enrolled in this meta-analysis. Results showed a significantly lower incidence of abnormal menstruation (relative risk: .40, 95% confidence interval [CI]: .20-.79, P = .008) after bariatric surgery. Moreover, bariatric surgery led to a decrease in serum insulin levels (mean difference [MD] = -13.12 mIU/L, 95% CI: -15.03 to -11.22, P < .00001), glucose (MD = -.91 mmol/L, 95% CI: -1.26 to -.56, P < .00001), triglyceride (MD = -.61 g/L, 95% CI: -.76 to -.46, P < .00001), total testosterone (MD = -.22 ng/mL, 95% CI: -.24 to -.20, P < .00001), dehydroepiandrosterone (DHEA) (MD = -25.34 μg/dL, 95% CI: -31.19 to -19.49, P < .00001), estradiol (MD = -25.13 pg/mL, 95% CI: -34.13 to -16.13, P < .00001), and anti-Mullerian hormone (AMH) (MD = -.40 ng/mL, 95% CI: -.67 to -.13, P = .003). Serum sex hormone binding globulin (SHBG) levels increased after bariatric surgery (MD = 43.99 nmol/L, 95% CI: 34.99-52.99, P < .00001).

Conclusion: Bariatric surgery can lower fasting insulin, glucose, and triglyceride levels, reduce the incidence of abnormal menstruation, decrease total serum testosterone, DHEA, estradiol, and AMH levels, and increase SHBG level for women with obesity of childbearing age who do not have PCOS. This meta-analysis indicated that bariatric surgery could be effective in improving reproductive function for women with severe obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soard.2021.09.008DOI Listing
January 2022

Tong‑fu‑li‑fei decoction attenuates immunosuppression to protect the intestinal‑mucosal barrier in sepsis by inhibiting the PD‑1/PD‑L1 signaling pathway.

Mol Med Rep 2021 12 11;24(6). Epub 2021 Oct 11.

Department of Intensive Care Unit, First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, Guizhou 550001, P.R. China.

The aim of the present study was to investigate the therapeutic effects of Tong‑fu‑li‑fei (TFL) decoction on sepsis‑induced injury to the intestinal mucosal barrier and the underlying mechanism. Cecal ligation and puncture (CLP) was used to establish a sepsis model in rats. The post‑surgery death of the rats was recorded to calculate the survival rate. A 4‑kD fluorescein isothiocyanate (FITC)‑dextran assay was used to evaluate the intestinal permeability of the rats. The pathological state of the intestine tissues was detected by hematoxylin and eosin staining and the ultrastructural changes in the endometrium were evaluated by transmission electron microscopy. Enzyme‑linked immunosorbent assay was used to determine the concentrations of interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α in the intestinal tissues and cells. The expression levels of SHP‑2 and PI3K were detected by reverse transcription‑quantitative PCR and western blotting. Sorting by flow cytometry was used to obtain pure dendritic cells (DC), CD8 T cells and natural killer cells. Western blotting was used to evaluate the expression levels of phosphorylated (p)‑AKT and AKT. The results demonstrated that the significantly decreased survival rate caused by CLP surgery was elevated by glutamine (Gln) and TFL treatment. Intestinal permeability was increased by CLP, and greatly suppressed by Gln or TFL treatment. Histopathological changes in the intestinal tissues, such as thinner barrier and atrophied mucosa, and ultrastructure changes such as sharply decreased microvilli and mitochondria dropsy, were observed on sepsis animals; these effects were ameliorated by the introduction of Gln or TFL. The upregulation of SHP‑2, PI3K and p‑AKT induced by CLP was reversed by TFL. The release of IL‑6 and TNF‑α was elevated and the expression of SHP‑2, PI3K and p‑AKT was suppressed in the co‑cultural system of DC cells and CD8 T cells by TFL. Overall, TFL decoction may attenuate immunosuppression to protect intestinal mucosal barrier in sepsis via inhibiting the programmed death1/programmed cell death ligand 1 signal pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2021.12480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524432PMC
December 2021

Correlation of Molecular Tumor Markers CA125, HE4, and CEA with the Development and Progression of Epithelial Ovarian Cancer.

Iran J Public Health 2021 Jun;50(6):1197-1205

Department of Obstetrics and Gynecology, Jining Maternal and Child Health and Family Planning Service Center, Jining, 272100, China.

Background: This study was designed to explore the levels of serum moleculartumor markers carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), and carcinoembryonic antigen (CEA) in patients with primary epithelial ovarian cancer, and their correlation with the progression of the cancer.

Methods: A total of 222 people were enrolled in this study admitted to Jining Maternal and Child Health and Family Planning Service Center from January 2016 to December 2017. There were 122 patients with primary epithelial ovarian cancer (ovarian cancer group), 50 patients with benign ovarian diseases (benign control group), and 50 healthy individuals (normal control group). The levels of serum CA125, CEA, and HE4 were detected by the electrochemical luminescence method and ELISA.

Results: The levels of serum CA125, HE4, and CEA in the ovarian cancer group were significantly higher than those in patients with the benign control group and the normal control group (<0.01). The levels of serum CA125, HE4, and CEA in the high clinical staging group (stage III and stage II), low differentiation group, comorbid ascites group, metastasis group, and recurrence group were significantly higher than those in the low clinical staging group (stage I and stage II), high + moderate differentiation group, non-ascites group, non-metastasis group, and non-recurrence group, respectively (all <0.05), and the levels of serum CA125, HE4, and CEA decreased significantly after treatment (<0.01).

Conclusion: The levels of serum CA125, HE4, and CEA are closely related to the development and progression of epithelial ovarian cancer, and combined detection of CA125, HE4 and CEA is of great significance for early diagnosis, disease development monitoring, and prognosis evaluation of epithelial ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18502/ijph.v50i6.6418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410970PMC
June 2021

Metformin and exenatide upregulate hepatocyte nuclear factor-4α, sex hormone binding globulin levels and improve hepatic triglyceride deposition in polycystic ovary syndrome with insulin resistance rats.

J Steroid Biochem Mol Biol 2021 11 31;214:105992. Epub 2021 Aug 31.

Department of Endocrinology, Shengjing Hospital of China Medical University, 110004, Shenyang, China. Electronic address:

Objective: To explore the efficacy and underlying mechanisms of metformin and exenatide in reversing reproductive and metabolic disturbances in letrozole combined with high-fat diet-induced polycystic ovary syndrome (PCOS) rats.

Methods: Rats with PCOS and insulin resistance (IR) were induced by intra-gastric instillation of letrozole combined with a high-fat diet and verified by histological screening of vaginal exfoliated cells. After metformin and exenatide supplementation, body weight, chow intake and ovarian morphology were observed. Serum biochemical profiles were analyzed using ELISA, while the levels of key anabolism-related proteins, including sex hormone binding globulin (SHBG), hepatocyte nuclear factor-4α (HNF-4α), PI3K, and AKT, were determined using western blotting.

Results: The estrus cycle and ovarian morphology of rats with PCOS and IR were significantly recovered following metformin and exenatide treatment, with decreased body weight and chow intake. Furthermore, PCOS-induced changes in metabolic disorders including IR and hepatic triglyceride (TG) deposition, and hyperandrogenemia were reversed by treatment with both drugs. Specifically, the levels of HNF-4α and SHBG in liver tissue of rats with PCOS and IR were upregulated significantly.

Conclusions: Both metformin and exenatide could recover the estrous cycle and ovarian morphology, reduce body weight and high-fat chow intake, and improve glycolipid metabolism disorders and hyperandrogenemia in PCOS with IR rat models. Interestingly, our findings also highlight the potential of both therapeutic agents for improving IR by regulating the liver PI3K/AKT pathway, reducing the deposition of hepatic TG, as well as upregulating the levels of SHBG and HNF-4α in PCOS with IR rat liver tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsbmb.2021.105992DOI Listing
November 2021

Oleic Acid and Insulin as Key Characteristics of T2D Promote Colorectal Cancer Deterioration in Xenograft Mice Revealed by Functional Metabolomics.

Front Oncol 2021 9;11:685059. Epub 2021 Aug 9.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, China.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high mortality worldwide. Type 2 diabetes mellitus (T2D), known as a risk factor of CRC, can promote the deterioration of CRC, but the underlying mechanism is elusive. In this study, we aimed to reveal the relationship between CRC and T2D from the perspective of small-molecule metabolism. First, a list of common dysregulated metabolites in CRC and T2D was obtained by retrieving existing metabolomics publications. Among these metabolites, oleic acid (OA) was found to be able to promote the proliferation and migration of colon carcinoma cell HCT116. Further experiments proved that insulin could significantly strengthen this promotion and showed a synergistic effect with OA. Mechanism study found that OA and insulin acted synergistically through the extracellular signal-regulated kinase (ERK)1/2/c-Myc/cyclin D1 pathway. In addition, the combination of ERK1/2 inhibitor SCH772984 and cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib showed a remarkable inhibitory effect on tumor growth . Taken together, the current study found that OA plays an important role in CRC development by using a functional metabolomics approach. More importantly, insulin and OA were confirmed to synergistically promote the deterioration of CRC and ERK1/2/c-Myc/cyclin D1 pathway. Our findings may shed light on CRC treatment among the T2D population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.685059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381473PMC
August 2021

Bilateral Subthalamic Nucleus Deep Brain Stimulation Improves Gastric Emptying Time in Parkinson Disease.

World Neurosurg 2021 10 31;154:e683-e688. Epub 2021 Jul 31.

Department of Neurosurgery, The First Affiliated Hospital of AnHui Medical University, Heifei, China. Electronic address:

Background: It is well-established that deep brain stimulation (DBS) can improve motor function in those with Parkinson disease (PD); however, its effects on gastrointestinal disorders remain unclear.

Methods: From January 2019 to December 2020, 26 patients with PD who had undergone subthalamic nucleus (STN) DBS were included in our study. The evaluated items included the pre- and postoperative dose of levodopa, Unified Parkinson's Disease Rating Scale, part III, scores with and without medication and stimulation, and gastric emptying time (expressed as the peak time of carbon-C dioxide excretion in the C-acetate breath test). Sex-, age-, and body weight-matched controls were recruited to test the gastric emptying time in healthy individuals.

Results: All the patients benefited from DBS. The Unified Parkinson's Disease Rating Scale, part III, scores had decreased from 48.5 ± 13.77 to 25.23 ± 8.59 without medication and 31.23 ± 11.4 to 13.92 ± 5.27 with medication. The levodopa equivalent dose had decreased from 1009.8 ± 291 mg to 707.65 ± 193.79 mg. The gastric emptying time was significantly prolonged in the patients with PD before DBS compared with the healthy control group (29.23 ± 6.58 minutes) and had improved to 35.19 ± 10.14 minutes with medication and 38.07 ± 11.17 minutes without medication after 3 months of STN stimulation. At 6 months postoperatively, the gastric emptying time was 32.3 ± 10.02 minutes without medication and 33.84 ± 10.79 minutes with medication.

Conclusions: A delayed gastric emptying time is associated with greater PD severity. Antiparkinsonian medications did not affect gastric emptying in patients with PD. STN DBS can improve both movement function and gastrointestinal motility in patients with PD in the long term. The exact mechanism by which DBS improves gastric emptying requires further exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.07.112DOI Listing
October 2021

O-glycosyltransferases from contributes to the biosynthesis of and Glycyrrhizin in .

Synth Syst Biotechnol 2021 Sep 14;6(3):173-179. Epub 2021 Jul 14.

Key Lab for Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Tsinghua University, Beijing, 100084, PR China.

Glycyrrhizin (GL) and Glycyrrhetic Acid 3-O-mono-β-D-glucuronide (GAMG) are the typical triterpenoid glycosides found in the root of licorice, a popular medicinal plant that exhibits diverse physiological effects and pharmacological manifestations. However, only few reports are available on the glycosylation enzymes involved in the biosynthesis of these valuable compounds with low conversion yield so far. In mammals, glycosyltransferases are involved in the phase II metabolism and may provide new solutions for us to engineer microbial strains to produce high valued compounds due to the substrate promiscuity of these glycosyltransferases. In this study, we mined the genomic databases of mammals and evaluated 22 candidate genes of O-glycosyltransferases by analyzing their catalytic potential for O-glycosylation of the native substrate, glycyrrhetinic acid (GA) for its glycodiversification. Out of 22 selected glycosyltransferases, only UGT1A1 exhibited high catalytic performance for biosynthesis of the key licorice compounds GL and GAMG. Molecular docking results proposed that the enzymatic activity of UGT1A1 was likely owing to the stable hydrogen bonding interactions and favorite conformations between the amino acid residues around substrate channels (P82~R85) and substrates. Furthermore, the complete biosynthesis pathway of GL was reconstructed in for the first time, resulting in the production of 5.98 ± 0.47 mg/L and 2.31 ± 0.21 mg/L of GL and GAMG, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.synbio.2021.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283272PMC
September 2021

Medium-term efficacy of arthroscopic debridement conservative treatment for knee osteoarthritis of Kellgren-Lawrence grades I-III.

World J Clin Cases 2021 Jul;9(19):5102-5111

Department of Orthopaedics, Shanghai Jing'an District Zhabei Central Hospital, Shanghai 200070, China.

Background: Arthroscopic debridement is a mature treatment for knee osteoarthritis (KOA). Due to the differences in the research subjects, methods, and efficacy evaluation indexes, there are great differences in the surgical efficacy reported in the literature.

Aim: To compare the medium-term efficacy of arthroscopic debridement and conservative treatment for KOA of Kellgren-Lawrence grades I-III.

Methods: Patients with KOA of Kellgren-Lawrence grades I-III who were admitted to the orthopedic clinic of our hospital from July 2018 to December 2018 and agreed to undergo arthroscopic surgery were included in an arthroscopic debridement group, and those who refused surgical treatment were included in a conservative treatment group. Gender, age, body mass index (BMI), side of KOA, American hospital for special surgery knee score (HSS score) before treatment, visual analogue scale (VAS) score during walking and rest before treatment, conservative treatment content, and surgical procedure were recorded. Outpatient visits were conducted at the 1, 3, 6, 12, and 24 mo after treatment in the two groups. The changes of HSS score and VAS score in each group before and after treatment were statistically analyzed, and the differences of HSS score and VAS score in different treatment stages between the two groups were also compared.

Results: In the conservative treatment group, there were 80 patients with complete follow-up data, including 20 males and 60 females, aged 58.75 ± 14.66 years old. And in the knee arthroscopic debridement group, there were 98 patients with complete follow-up data, including 24 males and 74 females, aged 59.27 ± 14.48 years old. There was no statistically significant difference in the general data (gender, age, BMI, side of KOA, Kellgren-Lawrence grade distribution, HSS score, and VAS score) between the two groups before treatment. The HSS scores of the conservative treatment group at the 1, 3, 6, 12, and 24 mo after treatment were significantly higher than that before treatment ( < 0.05). There was no statistical difference in HSS score of the conservative treatment group among the 1, 3, 6, 12, and 24 mo ( > 0.05). The HSS score of the knee arthroscopic debridement group at the 1 mo after surgery was significantly higher than that before surgery ( < 0.05). HSS scores of the knee arthroscopic debridement group at the 3, 6, 12, and 24 mo were significantly higher than those before surgery and at the 1 mo after surgery ( < 0.05). There were no statistically significant differences in HSS scores at the 3, 6, 12, and 24 mo after surgery ( > 0.05). HSS scores at the 3, 6, 12, and 24 mo were significantly higher in the arthroscopic debridement group than in the conservative treatment group ( < 0.05). There was no statistical difference in HSS scores between the two groups before treatment and at the 1 mo of follow-up ( > 0.05). VAS scores during walking and rest were significantly decreased in both groups, and the VAS score during rest was significantly lower in the arthroscopic debridement group than in the conservative treatment group, but there was no significant difference in the VAS score during walking between the two groups after treatment.

Conclusion: Compared with conservative treatment, arthroscopic debridement can significantly improve the knee resting pain and knee functional status of patients with KOA of Kellgren-Lawrence grades I-III within 2 years after treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v9.i19.5102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283583PMC
July 2021

Pathological changes and oxidative stress of the HPG axis in hypothyroid rat.

J Mol Endocrinol 2021 08 11;67(3):107-119. Epub 2021 Aug 11.

Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China.

Hypothyroidism is a common endocrine disease caused by a deficiency of thyroid hormones, which could affect the hypothalamus-pituitary-gonadal (HPG) axis and cause additional severe fertility problems. However, the pathogenesis of abnormal reproductive capacity caused by hypothyroidism and whether there are differences between females and males need more study. Here, we constructed a prolonged neonatal hypothyroid rat model using 6-propyl-2-thiouracil (PTU). H&E staining and RNA-sequencing were performed to detect histopathological and transcriptome changes. Our results indicated that the numbers of ventromedial hypothalamus nuclei were increased, and the number of pituitary chromophobes was sharply increased, whereas the proportion of pituitary acidophils and pituitary basophils were obviously reduced. The differentially expressed genes of the HPG axis organs were identified, and different tissues shared similar steroid hormone and oxidative stress-related terms in gene ontology analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis indicated oxidative stress, and apoptosis-related genes were more enriched in male hypothyroid pituitaries, whereas the serum levels of growth hormone, follicle-stimulating hormone, and luteinizing hormone that were detected by ELISA were also reduced more in male hypothyroid rats, suggesting that prolonged neonatal hypothyroidism may have a more significant impact on male pituitaries. Moreover, the multi-organ oxidative stress in hypothyroid rats was confirmed by the higher expression of oxidative stress-related genes, such as the Txnip. The increased level of oxidative stress may have contributed to the histopathological and transcriptome changes of HPG axis organs in the prolonged neonatal hypothyroidism rats, especially in male pituitaries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/JME-21-0095DOI Listing
August 2021

E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened.

J Cell Biol 2021 09 23;220(9). Epub 2021 Jun 23.

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.

The Hedgehog pathway, critical to vertebrate development, is organized in primary cilia. Activation of signaling causes the Hedgehog receptor Ptch1 to exit cilia, allowing a second receptor, Smo, to accumulate in cilia and activate the downstream steps of the pathway. Mechanisms regulating the dynamics of these receptors are unknown, but the ubiquitination of Smo regulates its interaction with the intraflagellar transport system to control ciliary levels. A focused screen of ubiquitin-related genes identified nine required for maintaining low ciliary Smo at the basal state. These included cytoplasmic E3s (Arih2, Mgrn1, and Maea), a ciliary localized E3 (Wwp1), a ciliary localized E2 (Ube2l3), a deubiquitinase (Bap1), and three adaptors (Kctd5, Skp1a, and Skp2). The ciliary E3, Wwp1, binds Ptch1 and localizes to cilia at the basal state. Activation of signaling removes both Ptch1 and Wwp1 from cilia, thus providing an elegant mechanism for Ptch1 to regulate ciliary Smo levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1083/jcb.202010177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236919PMC
September 2021

Is metoclopramide beneficial for the postpyloric placement of nasoenteric tubes? A systematic review and meta-analysis of randomized controlled trials.

Nutr Clin Pract 2022 Apr 22;37(2):316-327. Epub 2021 Jun 22.

Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Background: Metoclopramide is frequently prescribed as an adjuvant for the postpyloric placement of nasoenteric tubes (NETs). However, a recent meta-analysis showed that metoclopramide was not beneficial in adults. Thus, this study aimed to reevaluate the effect of metoclopramide on the postpyloric placement of NETs.

Methods: A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data was conducted up to August 2020 for randomized controlled trials (RCTs) comparing metoclopramide with placebo or no intervention. Trial sequential analysis (TSA) was used for the primary outcomes (the success rate of the postpyloric placement of NETs).

Results: Seven eligible RCTs that included 520 participants were identified. The results of the pooled effect sizes showed that metoclopramide significantly facilitated the postpyloric placement of NETs (relative risk [RR], 1.48; 95% CI, 1.11-1.97; P = .007; I = 37%). However, the risk-of-bias assessment and the TSA results indicated that the qualities of the RCTs and the sample sizes were insufficient to confirm the efficacy of metoclopramide. Further subgroup analysis revealed that successful postpyloric placement was more pronounced in studies in which spiral NETs were employed (RR, 1.85; 95% CI, 1.41-2.43; P < .001; I = 0%). Additionally, overall adverse events were minimal.

Conclusions: The evidence accumulated so far was not strong enough to demonstrate metoclopramide's beneficial effects on the postpyloric placement of NETs. Further high-quality, large-sample RCTs are required to elucidate the effects of metoclopramide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ncp.10725DOI Listing
April 2022
-->