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1.
Eur Spine J ; 33(6): 2322-2331, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38676728

ABSTRACT

PURPOSE: This study aimed to investigate the association between unilateral high-riding vertebral artery (HRVA) and morphological changes in the atlantoaxial joint (AAJ) and to determine whether unilateral HRVA is a risk factor for atlantoaxial osteoarthritis (AAOA). METHODS: We conducted a retrospective analysis of 2496 patients admitted to our medical center between January 2020 and December 2022 who underwent CT imaging of the cervical spine. Two hundred and seventy-two patients with unilateral HRVA (HRVA group) were identified and a respective 2:1 age- and sex-matched control group without HRVA was built. Morphological parameters, including C2 lateral mass settlement (C2 LMS), C1/2 coronal inclination (C1/2 CI), lateral atlanto-dental interval (LADI), and C1/2 relative rotation angle (C1/2 RRA) were measured. The degree of AAOA was recorded. Risk factors associated with AAOA were identified using univariate and multivariable logistic regression analyses. RESULTS: The study included 61.4% women, and the overall average age of the study population was 48.7 years. The morphological parameters (C2 LMS, C1/2 CI, and LADI) in AAJ were asymmetric between the HRVA and the non-HRVA sides in the HRVA group (p < 0.001). These differences in parameters (d-C2 LMS, d-C1/2 CI, and d-LADI) between the HRVA and the non-HRVA sides, and C1/2 RRA were significantly larger than those in the control group. Eighty-three of 816 patients (10.2%) with AAOA had larger values of d-C2 LMS, d-C1/2 CI, d-LADI, and C1/2 RRA compared with the patients without AAOA (p < 0.05). The multivariable logistic regression analysis indicated that unilateral HRVA [adjusted odds ratio (OR) = 2.6, 95% CI: 1.1-6.3, p = 0.029], age in the sixth decade or older (adjusted OR = 30.2, 95% CI: 16.1-56.9, p < 0.001), women (adjusted OR = 2.1, 95% CI: 1.0-5.6, P = 0.034) were independent risk factors for AAOA. CONCLUSION: Unilateral HRVA was associated with asymmetric morphological changes of nonuniform settlement of C2 lateral mass, lateral slip of atlas, and atlantoaxial rotation displacement. Besides age ≥ 60 years and females, unilateral HRVA is an independent risk factor for AAOA.


Subject(s)
Atlanto-Axial Joint , Vertebral Artery , Humans , Atlanto-Axial Joint/diagnostic imaging , Atlanto-Axial Joint/pathology , Female , Male , Middle Aged , Risk Factors , Vertebral Artery/diagnostic imaging , Vertebral Artery/pathology , Retrospective Studies , Adult , Aged , Tomography, X-Ray Computed , Osteoarthritis/diagnostic imaging , Osteoarthritis/pathology , Osteoarthritis/epidemiology , Cervical Vertebrae/diagnostic imaging , Osteoarthritis, Spine/diagnostic imaging , Osteoarthritis, Spine/epidemiology , Osteoarthritis, Spine/pathology
2.
J Environ Manage ; 351: 119997, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38160546

ABSTRACT

We report a novel modified semi-carbonized fiber (CF) prepared using cotton and acrylic clothes for derisking contaminated water to realize the resource utilization of discarded clothes in wastewater treatment. In this study, amphoteric and auxiliary modifiers were used to modify CFs for preparing amphoteric and amphoteric-auxiliary CFs. The basic physicochemical properties of different modified CFs were determined, and the microscopic morphology of modified CFs was detected. The isothermal adsorption characteristics of Cu(II) and Pb(II) on different modified CFs were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and material dose were compared. Physicochemical properties and microscopic morphology results proved that amphoteric and auxiliary modifiers were modified on the CF surface and changed the surface properties of CF. The adsorption capacities of Cu(II) and Pb(II) on modified CFs increased with the increase in equilibrium concentration of Cu(II) and Pb(II), and the isotherm was more suitable for Freundlich model fitting than that of the Langmuir model. The maximum adsorption capacities (qm) of Cu(II) and Pb(II) on different modified CFs were 60.72-81.26 mg/g and 102.58-161.72 mg/g, respectively, and presented the trend of amphoteric-auxiliary CFs > amphoteric CFs > CFs. Increasing pH and temperature and decreasing ionic strength and material dose were beneficial to Cu(II) and Pb(II) adsorption. The Cu(II) and Pb(II) adsorption process was a spontaneous, endothermic, and entropy-increasing reaction, and the adsorption rate was controlled by chemisorption. The adsorption amount of amphoteric-auxiliary CFs maintained about 65% of original materials after 3 times of regeneration. Electrostatic attraction, precipitation, complexation, and ion exchange were the main adsorption mechanisms. The cation exchange capacity and total pore volume of modified CFs were key to determining qm of Cu(II) and Pb(II).


Subject(s)
Lead , Water Pollutants, Chemical , Temperature , Cations , Adsorption , Water , Clothing , Water Pollutants, Chemical/chemistry , Kinetics , Hydrogen-Ion Concentration
3.
Neurobiol Dis ; 188: 106346, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37931884

ABSTRACT

Sprouting of mossy fibers, one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy, exhibits several uncommon axonal growth features and has been considered a paradigmatic example of circuit plasticity that occurs in the adult brain. Clarifying the mechanisms responsible may provide new insight into epileptogenesis as well as axon misguidance in the central nervous system. Methyl-CpG-binding protein 2 (MeCP2) binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. However, exploring the potential role of MeCP2 in the documented misguidance of axons in the dentate gyrus has not yet been attempted. In this study, a status epilepticus-induced decrease of neuronal MeCP2 was observed in the dentate gyrus (DG). An essential regulatory role of MeCP2 in the development of functional mossy fiber sprouting (MFS) was confirmed through stereotaxic injection of a recombinant adeno-associated virus (AAV) to up- or down-regulate MeCP2 in the dentate neurons. Chromatin immunoprecipitation sequencing (ChIP-seq) was performed to identify the binding profile of native MeCP2 using micro-dissected dentate tissues. In both dentate tissues and HT22 cell lines, we demonstrated that MeCP2 could act as a transcription repressor on miR-682 with the involvement of the DNA methylation mechanism. Further, we found that miR-682 could bind to mRNA of phosphatase and tensin homolog (PTEN) in a sequence specific manner, thus leading to the suppression of PTEN and excessive activation of mTOR. This study therefore presents a novel epigenetic mechanism by identifying MeCP2/miR-682/PTEN/mTOR as an essential signal pathway in regulating the formation of MFS in the temporal lobe epileptic (TLE) mice. SIGNIFICANCE STATEMENT: Understanding the mechanisms that regulate axon guidance is important for a better comprehension of neural disorders. Sprouting of mossy fibers, one of the most consistent findings in patients with mesial temporal lobe epilepsy, has been considered a paradigmatic example of circuit plasticity in the adult brain. Although abnormal regulation of DNA methylation has been observed in both experimental rodents and humans with epilepsy, the potential role of DNA methylation in this well-documented example of sprouting of dentate axon remains elusive. This study demonstrates an essential role of methyl-CpG-binding protein 2 in the formation of mossy fiber sprouting. The underlying signal pathway has been also identified. The data hence provide new insight into epileptogenesis as well as axon misguidance in the central nervous system.


Subject(s)
Epilepsy, Temporal Lobe , Epilepsy , MicroRNAs , Animals , Humans , Mice , Dentate Gyrus/metabolism , Epilepsy, Temporal Lobe/metabolism , Methyl-CpG-Binding Protein 2/genetics , Methyl-CpG-Binding Protein 2/metabolism , MicroRNAs/metabolism , Mossy Fibers, Hippocampal , TOR Serine-Threonine Kinases/metabolism
4.
J Chem Neuroanat ; 132: 102325, 2023 10.
Article in English | MEDLINE | ID: mdl-37595695

ABSTRACT

Anesthetics-induced disruption of dentate neurogenesis in the young brain is strongly suggested to contribute to delayed neurocognitive deficit. In postnatal rodents, the neurogenesis of the dentate gyrus (DG) is sequentially derived from the secondary dentate matrix, tertiary dentate matrix and subgranular zone (SGZ). However, the effects of anesthetics on the dentate neurogenesis derived from specific sites are poorly understood. To trace the new cells generated from the postnatal secondary dentate matrix, peak stage of the tertiary dentate matrix and early stage of the SGZ after isoflurane exposure, mice at postnatal day 1 (P1), P7 and P31 were injected with BrdU at 12 h before the exposure. We found that isoflurane exposure significantly reduced the numbers of proliferating cells (1 day old), immature granule cells (21 days old) or mature granule cells (42 days old) derived from the peak stage of the tertiary dentate matrix and postnatal secondary dentate matrix, but not from the SGZ. Quantitative assessment of BrdU-/BrdU+NeuN-positive cells and cleaved caspase-3 level in the DG indicated that the reduction was correlated with cell loss rather than neuronal differentiation. Mechanistically, we demonstrated that the PI3K/Akt/GSK-3ß pathway enriched by mRNA-sequencing is a requirement for the isoflurane-induced loss of 1-day-old proliferating cells generated from the tertiary dentate matrix. In addition, this study demonstrated that P1 and P7 mice, but not P31 mice exposure to isoflurane resulted in subsequent deficits in performance of the tasks of the Morris Water Maze.


Subject(s)
Isoflurane , Animals , Mice , Isoflurane/pharmacology , Bromodeoxyuridine , Glycogen Synthase Kinase 3 beta , Phosphatidylinositol 3-Kinases , Neurogenesis
5.
Global Spine J ; : 21925682231185332, 2023 Jul 08.
Article in English | MEDLINE | ID: mdl-37421142

ABSTRACT

STUDY DESIGN: A retrospective study was performed. OBJECTIVE: To investigate the prevalence and risk factors for adjacent segment disease (ASD) after anterior cervical discectomy and fusion (ACDF) and the clinical efficacy of revision surgery. METHOD: A total of 219 patients treated with ACDF were analyzed retrospectively. Demographic characteristics, including age, sex, body mass index (BMI) and bone mineral density (BMD), and radiographic measurements, including C2-C7 cervical sagittal vertical axis (cSVA), T1 slope (T1S), thoracic inlet angle (TIA) and C2-C7 Cobb angle, were analyzed. Modified Japanese Orthopaedic Association (mJOA) score and visual analog scale (VAS) score were used to evaluate patient function. Parameters were analyzed with Student's t test, and potential risk factors for ASD were further analyzed with multivariate logistic regression analysis. RESULTS: The incidence of ASD after ACDF surgeries was 21%. The severity of osteoporosis, BMI and C2-C7 cSVA were significantly higher in the ASD group than in the NASD group (P < .05). The preoperative and postoperative TIAs were lower in the ASD group (P < .05). Multivariate logistic regression analysis showed that a high BMI, severe osteoporosis and a high C2-C7 cSVA were risk factors for ASD after ACDF (P < .05). The postoperative TIA and postoperative T1S were also correlated with ASD (P < .05). CONCLUSION: Patients with a high BMI, severe osteoporosis, and a large C2-C7 cSVA after ACDF have a higher risk of ASD, while a large T1S and TIA may be protective factors. In addition, revision surgery can restore cervical spine balance in patients with ASD and promote better clinical outcomes.

6.
Spine J ; 23(7): 1054-1067, 2023 07.
Article in English | MEDLINE | ID: mdl-36868381

ABSTRACT

BACKGROUND CONTEXT: A high-riding vertebral artery (HRVA) can deviate too medially, too posteriorly, or too superiorly to allow the safe insertion of screws. However, it is unknown whether the presence of a HRVA is associated with morphological changes of the atlantoaxial joint. PURPOSE: To investigate the association between HRVA and atlantoaxial joint morphology in patients with and without HRVA. STUDY DESIGN: A retrospective case-control study and finite element (FE) analysis. PATIENT SAMPLE: A total of 396 patients with cervical spondylosis underwent multi-slice spiral computed tomography (MSCT) of cervical spine at our institutions from 2020 to 2022. OUTCOME MEASURES: A series of atlantoaxial joint morphological parameters, including C2 lateral mass settlement (C2 LMS), C1-2 sagittal joint inclination (C1-2 SI), C1-2 coronal joint inclination (C1-2 CI), atlanto-dental interval (ADI), lateral atlanto-dental interval (LADI), and C1-2 relative rotation angle (C1-2 RRA) were measured, and lateral atlantoaxial joints osteoarthritis (LAJs-OA) was recorded. The stress distribution on the C2 facet surface under different torques of flexion-extension, lateral bending, and axial rotation was analyzed by FE models. A 2-Nm moment was applied to all models to determine the range of motion (ROM). METHODS: A total of 132 consecutive cervical spondylosis patients with unilateral HRVA were enrolled in the HRVA group, and 264 patients without HRVA matched for age and sex were enrolled in the normal (NL) group. Atlantoaxial joint morphological parameters were compared between two sides of C2 lateral mass within HRVA or NL group, and between HRVA and NL groups. A 48-year-old woman with cervical spondylosis without HRVA was selected for cervical MSCT. A three-dimensional (3D) FE intact model of the normal upper cervical spine (C0-C2) was created. We established the HRVA model by simulating atlantoaxial morphological changes of unilateral HRVA with FE method. RESULTS: The C2 LMS was significantly smaller on the HRVA side than that on the non-HRVA side in the HRVA group, but C1-2 SI, C1-2 CI, and LADI on HRVA side were significantly larger than those on non-HRVA side. There was no significant difference between left and right sides in the NL group. The difference in C2 LMS (d-C2 LMS) between HRVA side and non-HRVA side in the HRVA group was larger than that in the NL group (P < 0.05). Meanwhile, the differences in C1-2 SI (d-C1/2 SI), C1-2 CI (d-C1/2 CI), and LADI (d-LADI) in the HRVA group were significantly larger than those in the NL group. The C1-2 RRA in the HRVA group was significantly larger than that in the NL group. Pearson correlations showed that d-C1/2 SI, d-C1/2 CI, and d-LADI were positively associated with d-C2 LMS (r=0.428, 0.649, 0.498, respectively, p<.05 for all). The incidence of LAJs-OA in the HRVA group (27.3%) was significantly larger than that in the NL group (11.7%). Compared with the normal model, the ROM of C1-2 segment declined in all postures of the HRVA FE model. We found a larger distribution of stress on the C2 lateral mass surface of the HRVA side under different moment conditions. CONCLUSIONS: We suggest that HRVA affects the integrity of the C2 lateral mass. This change in patients with unilateral HRVA is associated with the nonuniform settlement of the lateral mass and an increase in the lateral mass inclination, which may further affect the degeneration of the atlantoaxial joint because of the stress concentration on the C2 lateral mass surface.


Subject(s)
Atlanto-Axial Joint , Spinal Fusion , Spondylosis , Female , Humans , Middle Aged , Atlanto-Axial Joint/diagnostic imaging , Atlanto-Axial Joint/surgery , Finite Element Analysis , Vertebral Artery/diagnostic imaging , Retrospective Studies , Case-Control Studies , Spinal Fusion/methods , Biomechanical Phenomena , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Tomography, Spiral Computed , Range of Motion, Articular , Spondylosis/diagnostic imaging , Spondylosis/surgery
7.
Adv Healthc Mater ; 12(19): e2203118, 2023 07.
Article in English | MEDLINE | ID: mdl-36929289

ABSTRACT

Owing to the serious clinical side effects of intravenous Taxol, an oral chemotherapeutic strategy is expected to be promising for paclitaxel (PTX) delivery. However, its poor solubility and permeability, high first-pass metabolism, and gastrointestinal toxicity need to be overcome. A triglyceride (TG)-like prodrug strategy facilitates oral drug delivery by bypassing liver metabolism. However, the effect of fatty acids (FAs) in sn-1,3 on the oral absorption of prodrugs remains unclear. Herein, a series of TG-mimetic prodrugs of PTX is explored with different carbon chain lengths and degrees of unsaturation of FAs at the sn-1,3 position in an attempt to enhance oral antitumor effect and to guide the design of TG-like prodrugs. Interestingly, the different FA lengths exhibit great influence on in vitro intestinal digestion behavior, lymph transport efficiency, and up to fourfold differences in plasma pharmacokinetics. The prodrug with long-chain FAs shows a more effective antitumor effect, whereas the degree of unsaturation has a negligible impact. The findings illustrate how FAs structures affect the oral delivery efficiency of TG-like PTX prodrugs and thus provide a theoretical basis for their rational design.


Subject(s)
Prodrugs , Prodrugs/chemistry , Paclitaxel/chemistry , Fatty Acids , Drug Delivery Systems , Triglycerides
8.
Heliyon ; 9(1): e12812, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36699279

ABSTRACT

In this paper, a direct numerical simulation (DNS) of dielectric fluid flow subjected to unipolar injection under an alternating current (AC) electric field is carried out. The effect of frequency f of pulsed direct current (PDC) and AC on the transient evolution of electroconvection and their subcritical bifurcations are investigated in details. Electroconvection under PDC or AC tends to exhibit oscillating flow due to the periodic boundary condition of charge density and potential compared to the direct current (DC) case. The results demonstrate that under the PDC field, the linear criterion T c decreases with increasing frequency, while the nonlinear stability criterion T f is hardly affected. Under the AC field, a critical frequency f c  = 0.0316 is found, which separates electroconvection into two typical flow regimes-periodic flow regime (f < f c ) and inhibited flow regime (f ≥ f c )-depending on whether free charges can reach the collector electrode before electric field inversion. AC-electrohydrodynamics (EHD) systems promote various flow patterns with relatively lower voltage regimes than DC-EHD systems. These mechanisms of electroconvection under the PDC/AC field offer unique possibilities for fluid flow control in biological EHD-driven flow and portable EHD applications.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965575

ABSTRACT

@#Abstract: Objective To clone PE_PGRS35 gene of Mycobacterium tuberculosis(MTB),construct recombinant vector pET28a⁃PE_PGRS35,express and purify the PE_PGRS35 protein of MTB H37Rv heterologously,and explore a new target against MTB after bioinformatics analysis. Methods The PE_PGRS35 coding gene was amplified by PCR and used to construct the expression vector pET28a⁃PE_PGRS35 by recombinant cloning technology,which was transformed to E. coli BL21(DE3)after successful sequencing and induced by using IPTG. The obtained PE_PGRS35 protein was purified by Ni column affinity chromatography and analyzed by bioinformatics. Results The pET28a⁃PE_PGRS35 prokaryotic expression vector was constructed correctly as identified by sequencing. The PE_PGRS35 protein was mainly expressed in the form of inclusion bodies,with a relative molecular mass of about 53 000 and a purity of 90%. Bioinformatics analysis showed that PE_PGRS35 protein was an acid⁃labile protein,with main secondary structure of β⁃sheet and random coil,and no transme⁃ mbrane region,which was presumed to be an extramembrane protein with 39 phosphorylation sites and two conserved domains. Total 10 proteins,including Rv1769,PPE8,PPE64,PPE54,PPE24,PPE16,PPE35,PPE6,PPE28 and PE2, interacted with PE_PGRS35 protein. Conclusion PE_PGRS35 protein with high purity was successfully obtained,which provided a reference for the further development of new targets for drugs against MTB.

10.
Med Oncol ; 40(2): 68, 2022 Dec 31.
Article in English | MEDLINE | ID: mdl-36586018

ABSTRACT

Dinaciclib is a selective cyclin-dependent kinase inhibitor, but its radiosensitizing effect remains unclear. The aim of this study is to investigate the radiosensitizing effect of Dinaciclib on cervical cancer cells. Two cervical cancer cell lines, Hela and Siha, were selected, and the IC50 was determined by CCK8. The radiosensitizing effect of Dinaciclib was verified by plate cloning assay, and the G2/M phase arrest and apoptosis of IR cells were verified by flow cytometry. Immunofluorescence assay was used to verify the formation of γH2AX foci following DNA damage. Western blot was performed to detect cell cycle, apoptosis, autophagy, and DNA damage-related pathways. Dinaciclib increased the cell sensitivity to IR. IR induced G2/M phase arrest and apoptosis, and Dinaciclib enhanced this effect. Further, Dinaciclib delayed DNA repair, including non-homologous end joining repair and homologous recombination repair, and reduced the expression of DNA repair proteins Ku80 (SiHa cells), Ku70, and RAD51, as well as the expression of apoptotic marker Bcl-2. The expression of autophagy marker Beclin1 induced tumor cell death and increased the formation of DNA damage marker γH2AX foci. Dinaciclib improves the sensitivity of cervical cancer cells to IR by inducing cell cycle arrest, delaying DNA repair, and increasing apoptosis. However, further research is needed to unravel the complexity of DNA repair pathways.


Subject(s)
Radiation-Sensitizing Agents , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Cell Line, Tumor , Cell Cycle Checkpoints , Apoptosis , Protein Kinase Inhibitors/pharmacology , Radiation-Sensitizing Agents/pharmacology , Cyclin-Dependent Kinases , Radiation Tolerance
11.
Int Orthop ; 46(12): 2897-2906, 2022 12.
Article in English | MEDLINE | ID: mdl-36153365

ABSTRACT

PURPOSE: To evaluate the long-term clinical outcomes of degenerative lumbar scoliosis (DLS) with the administration of multisegment transforaminal lumbar interbody fusion (TLIF) combined with Ponte osteotomy long-level fixation fusion, as well as to identify the factors affecting health-related quality of life (HRQOL). METHODS: This was a retrospective single-centre study involving comprehensive clinical data. The Oswestry Disability Index (ODI), visual analog scale (VAS) outcomes, and Scoliosis Research Society (SRS-22) questionnaire were recorded to assess HRQOL. A correlation analysis was performed to determine the association between HRQOL and radiographic parameters. RESULTS: A total of 41 consecutive patients (15 males and 26 females) met the inclusion criteria with a follow-up of 8.62 ± 1.20 years. Factors associated with HRQOL were significantly improved post-operation. Global sagittal parameters, including the sagittal vertebral axis (SVA) and T1 pelvic angle (TPA), and local parameters, including apical vertebral translation (AVT) and apical vertebral rotation (AVR), were significantly improved at the last follow-up. Significantly strong correlations between each clinical and radiographic parameter were demonstrated. Moreover, a multiple linear regression analysis demonstrated that the differences in AVT and AVR were significantly correlated with the difference in lumbar lordosis (LL), which was significantly correlated with the differences in SVA and TPA. CONCLUSION: The surgical treatment of DLS with multisegment TLIF accompanied by Ponte osteotomy and long-level fixations improved the quality of life of patients with a long-term effect. AVR correction is an important factor for LL restoration that significantly correlates with improvements in the sagittal balance parameters SVA and TPA, which are key factors for guaranteeing good HRQOL.


Subject(s)
Scoliosis , Spinal Fusion , Humans , Male , Female , Spinal Fusion/adverse effects , Scoliosis/diagnostic imaging , Scoliosis/surgery , Scoliosis/etiology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Retrospective Studies , Quality of Life , Follow-Up Studies , Treatment Outcome , Osteotomy/adverse effects , Pons
12.
Eur J Pharm Biopharm ; 176: 122-132, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35643367

ABSTRACT

Oral administration of chemotherapy agents, such as docetaxel (DTX), is expected to reduce side effects significantly and increase dosing frequency. However, they often suffer from poor oral bioavailability, impeding their oral application. Dietary lipids such as triglycerides favor lymphatic transport nor vein system, bypassing the first-pass metabolism. Inspired by this concept, we developed a triglyceride-like prodrug of DTX (named as OATG) and explored the effect of lipid types on the OATG oral delivery. The plasma profile in rats revealed that long chain triglyceride (LCT)-based lipid formulations (LBLF) were more promising for OATG delivery than medium chain triglyceride (MCT) ones. The OATG LBLF elicited a markedly enhanced absorption compared with oral Taxotere or DTX LBLF, resulting in relative bioavailability 6.11 or 2.47-fold higher, respectively. The coincident intestinal behaviors of lipid excipients and TG-like prodrug facilitate the oral absorption of the prodrug. The effectiveness of the prodrug formulation was also examined in beagles with absolute bioavailability up to 41.08%, in sharp contrast to that of control DTX group (8%). Besides, the OATG oral formulation could be schedule-intensively administrated with no hypersensitivity, gastrointestinal and hematological toxicity. The current strategy provides an effective lipid formulation and a promising chance for chemotherapy at home.


Subject(s)
Prodrugs , Administration, Oral , Animals , Biological Availability , Docetaxel/pharmacology , Dogs , Intestinal Absorption , Intestines , Rats , Triglycerides/metabolism
13.
Acta Neurobiol Exp (Wars) ; 82(1): 96-105, 2022.
Article in English | MEDLINE | ID: mdl-35451427

ABSTRACT

Studies on rodents and nonhuman primates suggest that exposure to anesthetics, particularly in the young brain, is associated with neuronal apoptosis as well as hippocampal­dependent cognitive dysfunction. Disruption of the development of dentate gyrus may play an important role in anesthetics­induced neurotoxicity. However, the anesthetics triggered molecular events in the dentate gyrus of the developing brain are poorly understood. By integrating two independent data sets obtained from miRNA­seq and mRNA­seq respectively, this study aims to profile the network of miRNA and potential target genes, as well as relevant events occurring in the dentate gyrus of isoflurane exposed 7­day­old mice. We found that a single four hours exposure to isoflurane yielded 1059 pairs of differently expressed miRNAs/target genes in the dentate gyrus. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further indicates that dysregulated miRNAs/target genes have far­reaching effects on the cellular pathophysiological events, such as cell apoptosis, axon development, and synaptic transmission. Our results would greatly broaden our functional understanding of the role of miRNA/target gene in the context of anesthetics­induced neurotoxicity.


Subject(s)
Anesthetics , Isoflurane , MicroRNAs , Anesthetics/pharmacology , Animals , Dentate Gyrus , Hippocampus , Isoflurane/toxicity , Mice , MicroRNAs/genetics
14.
Clin Chim Acta ; 531: 389-398, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35487250

ABSTRACT

BACKGROUND: Although they are involved in the progression of PCa, the use of sex steroid hormones in urinary exosomes as biomarkers for PCa remains obscure. Here, the potential use of sex steroid hormones in urinary exosomes as biomarkers was investigated for the prediction of early-stage PCa to assist in clinical diagnosis. METHODS: Two hundred and eighty-six participants were randomly recruited, 231 patients with PCa and 55 healthy controls. According to their Gleason scores (GSs), the patients with PCa were divided into two groups, mild PCa (GS6) (n = 116) and severe (≥GS7) group (n = 115). The concentrations of 8 sex steroid hormones in urinary exosomes were quantitated using liquid chromatography tandem mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS/MS). RESULTS: The results showed that the levels of 7 out of 8 sex steroids including dehydroepiandrosterone (DHEA), dehydroepiandrosteronesulfate (DHEAS), androstenedione (A4), testosterone (T), progesterone (P), dihydrotestosterone (DHT), and estrone (E1), but not estradiol (E2) in urinary exosomes, were not only distinguished the PCa patients from healthy controls, can also differentiate between patients with mild and severe PCa. Of the 8 selected urinary exosomal biomarkers, DHEA, DHEAS, T, and DHT were finally screened further to build the regression model, and the detection method of the 4 biomarkers-combined achieved an area under the ROC curve (AUC) of 0.854 and predictive accuracy of 78.2%. CONCLUSION: Our data showed the use of exosomal sex steroids in urine could be as biomarkers for predicting PCa for the first time. This finding would supply a novel insight for PCa diagnosis.


Subject(s)
Exosomes , Prostatic Neoplasms , Androstenedione , Biomarkers , Dehydroepiandrosterone , Dihydrotestosterone , Humans , Male , Prostatic Neoplasms/diagnosis , Tandem Mass Spectrometry/methods , Testosterone
15.
PLoS One ; 17(1): e0261537, 2022.
Article in English | MEDLINE | ID: mdl-35051182

ABSTRACT

Mental health is a major public health issue that affects social development. This study aims to explore the psychological state of residents of Hainan Island and its influencing factors during the COVID-19 pandemic and to provide a scientific basis for the formulation of psychological counseling measures to be used after the pandemic. We used the nonprobability snowball sampling method to conduct an online survey from February 21 to February 28, 2020, and collected a sample of 533 respondents. Using a binary logistic regression model and network analysis, the psychological state of residents and the main factors were analyzed during the concentrated outbreak of COVID-19 (from January 20 to February 16, 2020). The study found that during the pandemic, 92.7% of the respondents were in a poor state of mind, and 54.2% experienced severe psychological stress. The mental state is spatially expressed as a pattern of "high in the middle and low in the surroundings." Second, within the four-week sample, the overall psychological tension showed an inverted U-shaped trend. Respondents feeling stressed were most common in the second week, when they accounted for 87.99% of the total. Third, individual characteristics such as gender, age, fixed expenditure, and family size significantly affect the mental state. Women, the elderly, residents with fixed expenditures, and residents with large families are at greater risk of psychological stress. Finally, external factors such as the distance between residents and the location of cases and the node degree of the pandemic transmission network have a significant impact on the psychological state. However, residents in the least developed areas of Hainan Island, which are far away from active cases and have a low node degree, are more prone to psychological pressure. The government needs to pay special attention to these groups when constructing a long-term mechanism of psychological crisis intervention and increase public health resource investment in underdeveloped areas.


Subject(s)
COVID-19/psychology , Mental Health , Stress, Psychological/psychology , Adolescent , Adult , Aged , Aged, 80 and over , China , Cross-Sectional Studies , Female , Health Surveys , Humans , Male , Middle Aged , Pandemics , Young Adult
16.
Water Environ Res ; 94(1): e1661, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34779546

ABSTRACT

A life-cycle assessment (LCA) study was completed to assess the environmental impacts of an on-site wastewater treatment system in the fresh-cut fruit processing industry consisting of a membrane bioreactor (MBR), followed by reverse osmosis (RO) and ultraviolet (UV) disinfection. The system boundaries comprised raw materials extraction and processing, transportation, construction, operation, and waste disposal. SimaPro 8.0.4.26 was used as the software tool, supported by two impact assessment methods (ReCiPe v1.11 and TRACI v2.1). Analysis showed that the treatment capacity of the MBR and tertiary technologies contributed the least damage to the ecosystem when compared with the other three scenarios and can provide water for reuse. Treating wastewater in municipal wastewater treatment plants (WWTPs) mitigated eutrophication like the MBR system but resulted in more environmental impacts from climate change and human health when compared with the on-site treatment system. Findings will be informative to stakeholders in the fresh-cut agri-food sector seeking input into selecting the appropriate treatment approach, with water reuse a goal. PRACTITIONER POINTS: Life-cycle analysis was completed on a fruit processing facility using MBR + RO + UV. On site treatment with MBR + RO UV provides least amount of environmental impact. Use of MBR + RO + UV treatment on fruit wastewater allows for water reuse. ReCiPe v1.11 and TRACI v2.1 give similar LCA results, with TRACI recommended for North American analysis.

17.
Chin J Nat Med ; 19(9): 656-665, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34561076

ABSTRACT

The first-generation taxanes (including paclitaxel and docetaxel) are widely used for the treatment of various cancers in clinical settings. In the past decade, a series of new-generation taxanes have been developed which are effective in the inhibition of tumor resistance. However, intravenous (i.v.) infusion is still the only route of administration, and may result in serious adverse reactions with respect to the utilization of Cremophor EL or Tween-80 as solvent. Besides, the dosing schedule is also limited. Therefore, oral administration of taxanes is urgently needed to avoid the adverse reactionss and increase dosing frequency. In this review, we first outlined the discovery and development of taxane-based anticancer agents. Furthermore, we summarized the research progress on the oral formulations of taxanes and proposed some thoughts on the future development of oral taxane formulations.


Subject(s)
Antineoplastic Agents, Phytogenic , Antineoplastic Agents , Docetaxel , Drug Compounding , Paclitaxel , Taxoids
18.
J Cell Mol Med ; 25(3): 1613-1623, 2021 02.
Article in English | MEDLINE | ID: mdl-33410269

ABSTRACT

Spinal supraspinous ligament (SL) osteogenesis is the key risk of ankylosing spondylitis (AS), with an unclear pathogenesis. We previously found that transforming growth factor ß1 (TGF-ß1), bone morphogenetic proteins (eg BMP2) and type III TGF-ß1 receptor (TßRIII) expression were markedly up-regulated in AS-SLs. However, the roles of these closely related molecules in AS are unknown. Here, we showed that BMP2, TGF-ß1, TßRIII and S100A4 (a fibroblast marker) were abundant in active osteogenic AS-SL tissues. In vitro, AS-SL fibroblasts (AS-SLFs) showed high BMP2, TGF-ß1 and TßRIII expression and auto-osteogenic capacity. We further evaluated the role of TßRIII in the osteogenesis of normal SLFs. BMP2 combined with TGF-ß1 induced the osteogenesis of TßRIII-overexpressing SLFs, but the activity was lost in SLFs upon TßRIII knockdown. Moreover, our data suggested that BMP2 combined with TGF-ß1 significantly activated both TGF-ß1/Smad signalling and BMP2/Smad/RUNX2 signalling to induce osteogenesis of SLFs with TßRIII up-regulation. Furthermore, our multi-strategy molecular interaction analysis approach indicated that TGF-ß1 presented BMP2 to TßRIII, sequentially facilitating BMP2 recognition by BMPR1A and promoting the osteogenesis of TßRIII-overexpressing SLFs. Collectively, our results indicate that TGF-ß1 combined with BMP2 may participate in the osteogenic differentiation of AS-SLF by acting on up-regulated TßRIII, resulting in excessive activation of both TGF-ß1/Smad and BMP2/BMPR1A/Smad/RUNX2 signalling.


Subject(s)
Fibroblasts/metabolism , Osteogenesis/genetics , Receptors, Transforming Growth Factor beta/genetics , Spondylitis, Ankylosing/etiology , Spondylitis, Ankylosing/metabolism , Biomarkers , Cells, Cultured , Disease Susceptibility , Gene Expression Regulation , Humans , Immunohistochemistry , Ligaments , Receptors, Transforming Growth Factor beta/metabolism , S100 Calcium-Binding Protein A4/genetics , S100 Calcium-Binding Protein A4/metabolism , Spondylitis, Ankylosing/pathology , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism
19.
Arch Microbiol ; 203(2): 719-723, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33047173

ABSTRACT

A Gram-stain-negative, rod-shaped, facultatively anaerobic, motile and spore-forming strain designated FJAT-44921T was isolated from red mud collected from Chiping County, Shandong Province, China. The 16S rRNA gene sequence result showed that strain FJAT-44921T shared a low sequence identity (96.6%) with the members of the genus Bacillus. Growth was observed at pH 8.0-10.0 (optimum pH 9.0), 10-40 °C (optimum 20-25 °C) with 0-8% (v/w %) NaCl (optimum 4-6 v/w %). FJAT-44921T consists of MK-7 as the isoprenoid quinone and meso-2,6-diaminopimelic acid as the cell-wall diamino acid. The predominant fatty acids were anteiso-C15:0, iso-C15:0, C16:0, and anteiso-C17:0. The polar lipids were diphosphatidylglycerol, phosphatidyl glycerol, phosphatidylmethylethanolamine, unidentified phospholipid, and unidentified aminophospholipid. The genomic DNA G + C content was 37.3 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between FJAT-44921T and other closely related Bacillus members were lower than the recognized threshold values of ANI (95-96%) and dDDH (70%) recommended as the criterion for interspecies identity. The type strain is FJAT-44921T (=CCTCC AB 2016196T =DSM 104630T).


Subject(s)
Aluminum Oxide , Bacillus/classification , Soil Microbiology , Bacillus/genetics , Base Composition , Diaminopimelic Acid/chemistry , Fatty Acids/chemistry , Nucleic Acid Hybridization , Phospholipids/chemistry , Phylogeny , RNA, Ribosomal, 16S/genetics , Species Specificity
20.
Article in English | WPRIM (Western Pacific) | ID: wpr-888795

ABSTRACT

The first-generation taxanes (including paclitaxel and docetaxel) are widely used for the treatment of various cancers in clinical settings. In the past decade, a series of new-generation taxanes have been developed which are effective in the inhibition of tumor resistance. However, intravenous (i.v.) infusion is still the only route of administration, and may result in serious adverse reactions with respect to the utilization of Cremophor EL or Tween-80 as solvent. Besides, the dosing schedule is also limited. Therefore, oral administration of taxanes is urgently needed to avoid the adverse reactionss and increase dosing frequency. In this review, we first outlined the discovery and development of taxane-based anticancer agents. Furthermore, we summarized the research progress on the oral formulations of taxanes and proposed some thoughts on the future development of oral taxane formulations.

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