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1.
Clin Pharmacokinet ; 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36738401

RESUMO

PURPOSE: This study evaluated the effect of body mass index (BMI) on pharmacokinetic (PK) and pharmacodynamic (PD) parameters of insulin degludec in healthy Chinese males, depending on an euglycemic glucose clamp study. METHODS: Sixty-five healthy male subjects were divided into four groups according to quartile of BMI value. Group A: BMI ≤ 20.7 kg/m2; group B: 20.7 < BMI ≤ 22.5 kg/m2; group C: 22.5 < BMI ≤ 23.6 kg/m2; group D: BMI > 23.6 kg/m2. Each volunteer received a single subcutaneous dose (0.4 U/kg) of insulin degludec and accepted a 24-h euglycemic glucose clamp study. The primary PK parameters were maximum observed drug concentration (Cmax) and the area under the curve (AUCINS) for the specified time intervals. The primary PD parameters were the time to the start of glucose infusion (Tonset), maximal glucose infusion rate (GIRmax) and area under the curve (AUCGIR) for the specified time intervals. The differences of these PK/PD parameters were compared among groups. RESULTS: Cmax and the AUC of insulin (0-6 h, 6-12 h and 0-24 h) were more than onefold higher in group A than those in groups B, C, D, and the concentration-time curve of group A was significantly shifted to the left compared with the other three groups. The GIRmax, total AUCGIR, and AUCGIR for each time interval were significantly higher in group A than those in other three groups. The proportion of AUCGIR in group A was the lowest proportion among four groups seen in the late stage. Multiple linear regression analysis showed that BMI was negatively correlated with AUCGIR,0-24 h. CONCLUSIONS: Insulin degludec in healthy Chinese male subjects with BMI ≤ 20.7 kg/m2 had a faster absorption, clearance, and a stronger glucose-lowering effect, but a steeper decrease of insulin action in the late stage after dosing.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36735823

RESUMO

The artificial integration of inorganic materials onto polymers to create the analogues of natural biocomposites is an attractive field in materials science. However, due to significant diversity in the interfacial properties of two kinds of materials, advanced synthesis methods are quite complicated and the resultant materials are always vulnerable to external environments, which limits their application scenarios and makes them unsuitable for scalable production. Herein, we report a simple and universal approach to achieve robust and scalable surface mineralization of polymers using a rationally designed triple functional molecular bridge of fluorosilane, 3-[(perfluorohexyl sulfonyl) amino] propyltriethoxy silane (PFSS). In a two-step solution deposition, the fluoroalkyl and siloxane of the PFSS take charge of its adhesion and immobilization onto polymers by hydrophobic interaction and wrapping-like chemical cross-linking, and then the assembly and growth of inorganic nanoclusters for integration are achieved by strong chemical coordination of PFSS sulfonamide. The versatile mineralization of inorganic oxides (e.g., TiO2, SiO2, and Fe2O3) onto chemically inert polymer surfaces was realized very well. The resultant mineralized materials exhibit robust and multiple functionalities for hostile applications, such as hydrophilic membranes for removing oils in strong acidic and alkaline wastewaters, fabrics with advanced anti-bacteria for healthy wearing, and plates with strong mechanical performance for better use. Experimental results and theoretical calculations confirmed the homogenous distribution of the PFSS onto polymers via cross-linking for robust coordination with inorganic oxides. These results demonstrate a skillful enlightenment in the design of high-performance mineralized polymer materials used as membranes, fabrics, and medical devices.

3.
Ann Acad Med Singap ; 52(1): 8-16, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36730801

RESUMO

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION: This study demonstrates the benefit of early administration of the third dose among cancer patients.

4.
J Agric Food Chem ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722627

RESUMO

Pyrimorph is a carboxylic acid amide (CAA) fungicide, which shows excellent activity against oomycetes such as pepper phytophthora blight, tomato late blight, and downy mildew of cucumber. It works mainly by inhibiting the biosynthesis of cell wall of oomycetes. However, pyrimorph also shows weak activity of inhibiting mitochondrial complex III, which is the first CAA fungicide found to act on mitochondria. To improve this effect on mitochondria and develop fungicides that may have a novel mechanism of action, in this paper, by disassembling pyrimorph and conjugating the fragments with the mitochondrial-targeted delivery system (triphenylphosphonium), three series of mitochondrial-targeting analogues of pyrimorph were designed and synthesized. The results show that the pyridine-containing 1,1-diaryl is the core module of inhibition mitochondrial function of pyrimorph. Among these conjugates, compound 3b with a short linker showed the highest and broad-spectrum fungicidal activity, strong respiratory inhibition activity, and adenosine 5'-triphosphate synthesis inhibition activity, suggesting its potential as a fungicide candidate. 3b exhibited greatly improved action on mitochondria, such as by destroying the mitochondrial function of pathogens, causing mitochondrial swelling, weakening its influence on cell wall morphology, and so on. More importantly, this study provides a method to strengthen the drugs or pesticides with weak mitochondrial action, which is of special significance for developing mitochondrial bioactive molecules with the novel action mechanism.

5.
Chem Commun (Camb) ; 59(9): 1197-1200, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36629149

RESUMO

Co3ZnC can efficiently boost the activity of Co@N, O co-doped carbons for hydrogen evolution. The results show that moderate Co3ZnC plays key roles in achieving an appropriate weighted Co 3d band centre, enhancing charger transfer and thus optimizing the electrochemical active surface area. Thus, a low overpotential of ∼219 mV can drive a high current density of 1000 mA cm-2 under the favourable condition of moderate Co3ZnC.

6.
Nat Prod Res ; : 1-10, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36657401

RESUMO

The content of 4 6',7'-dihydroxybergamottin (DHB), bergamottin, isoimperatorin and epoxybergamottin of six pomelos produced in China were detected by High-performance liquid chromatography-diode array detection and their safety of related medicines was evaluated by inhibition of medium concentration (IC50) of cytochrome oxidases CYP450-like. The results showed that the total content of the four furanocoumarins in these pomelo juices from high to low in order was Guanximi pomelo > Liangping pomelo > Pinghemi pomelo > grapefruit > Huyou > Shatian pomelo. The concentration of isoimperatorin in grapefruit, DHB, bergamottinand and isoimperatorin in Liangping, bergamottin and epoxybergamottin in Pinghemi and all the four furanocoumarins in Guanximi were exceeded the corresponding IC50; although Huyou and Shatian contained some furanocoumarins, they did not exceed IC50. Therefore, when taking drugs metabolised by CYP450-like enzymes, Guanximi, Liangping, Pinghemi, and grapefruit should be avoided to consume, but it is relatively safe to eat Huyou and Shatian.

7.
Clin Biochem ; 113: 64-69, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36610469

RESUMO

BACKGROUND: α-thalassemia is an inherited blood disorder caused by variants in the α-globin gene cluster. Identification of the pathogenic α-globin gene variants is important for the diagnosis and management of thalassemia. METHODS: Two suspected families from Xiantao, Hubei Province were recruited in this study. The family members underwent hemoglobin testing. Polymerase Chain Reaction based reverse dot blot (PCR-RDB) was employed to identify the known variants. Next-generation sequencing (NGS) and third-generation sequencing (TGS) were performed to screen the potential disease-causing variants, which were validated by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). RESULTS: Hematological analysis suggested that proband A had α-thalassemia traits, and proband B had HbH disease traits. However, only a -α3.7 mutation had been detected by PCR-RDB and NGS in the proband of family B. Subsequent TGS identified a novel 10.3 kb deletion (NC_000016.10:g.172342-182690del) covering the HBA1, HBQ1 and HBA2 genes in the α-globin gene cluster in both family A and B, which was confirmed by Sanger sequencing and MLPA. These results indicated that the novel deletion is likely responsible for α-thalassemia. CONCLUSION: A novel α-thalassemia deletion was identified for the two families by TGS. Our work broadened the molecular spectrum of α-thalassemia, and was beneficial for the diagnosis, genetic counseling and management of α-thalassemia.

8.
Comput Struct Biotechnol J ; 21: 601-613, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36659922

RESUMO

Random mutagenesis is the natural opportunity for proteins to evolve and biotechnologically it has been exploited to create diversity and identify variants with improved characteristics in the mutant pools. Rational mutagenesis based on biophysical assumptions and supported by computational power has been proposed as a faster and more predictable strategy to reach the same aim. In this work we confirm that substantial improvements in terms of both affinity and stability of nanobodies can be obtained by using combinations of algorithms, even for binders with already high affinity and elevated thermal stability. Furthermore, in silico approaches allowed the development of an optimized bispecific construct able to bind simultaneously the two clinically relevant antigens TNF-α and IL-23 and, by means of its enhanced avidity, to inhibit effectively the apoptosis of TNF-α-sensitive L929 cells. The results revealed that salt bridges, hydrogen bonds, aromatic-aromatic and cation-pi interactions had a critical role in increasing affinity. We provided a platform for the construction of high-affinity bispecific constructs based on nanobodies that can have relevant applications for the control of all those biological mechanisms in which more than a single antigen must be targeted to increase the treatment effectiveness and avoid resistance mechanisms.

9.
Micromachines (Basel) ; 14(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36677244

RESUMO

Atmospheric particulate pollution poses a great danger to the environment and human health, and there is a strong need to develop equipment for collecting and separating particulate matter of different particle sizes to study the effects of particulate matter on human health. A virtual impactor is a particle separation device based on the principle of inertial separation which provides scientific guidance for identifying the composition characteristics of particles. Much existing virtual impactor research focuses on the design of structural dimensions with little exploration of the effect of fluid properties on performance. In this paper, a microfluidic chip with a cutoff diameter of 1.85 µm was designed based on computational fluid dynamics and numerically simulated via finite element analysis to analyze important parameters such as inlet flow rate, splitting ratio and fluid properties. By numerical simulation of the split ratio, we found that the obtained collection efficiency curves could not be combined into one characteristic curve by the Stk0.5 scaling method. We therefore propose a modified Stokes number equation for predicting the cutoff diameter at different splitting ratios. The collection efficiency curves of different fluids as microfluidic chip media were plotted, and the results show that the cut particle size was reduced from 2.5 µm to 1.85 µm after replacing conventional fluid air with CO2 formed by dry ice sublimation. This is a decrease of approximately 26%, which is superior to other existing methods for reducing the cutoff diameter.

10.
Pharmaceutics ; 15(1)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678909

RESUMO

Extracellular vesicles (EVs) are lipid bound particles derived from their original cells, which play critical roles in intercellular communication through their cargoes, including protein, lipids, and nucleic acids. According to their biogenesis and release pathway, EVs can be divided into three categories: apoptotic vesicles (ApoVs), microvesicles (MVs), and small EVs (sEVs). Recently, the role of EVs in oral disease has received close attention. In this review, the main characteristics of EVs are described, including their classification, biogenesis, biomarkers, and components. Moreover, the therapeutic mechanism of EVs in tissue regeneration is discussed. We further summarize the current status of EVs in pulp/periodontal tissue regeneration and discuss the potential mechanisms. The therapeutic potential of EVs in pulp and periodontal regeneration might involve the promotion of tissue regeneration and immunomodulatory capabilities. Furthermore, we highlight the current challenges in the translational use of EVs. This review would provide valuable insights into the potential therapeutic strategies of EVs in dental pulp and periodontal regeneration.

11.
Regen Biomater ; 10: rbac108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36683746

RESUMO

Skin defect is common in daily life, but repairing large skin defects remains a challenge. Using biomaterials to deliver biochemical or physical factors to promote skin tissue regeneration is of great significance for accelerating wound healing. Specific surface micropatterns on biomaterials could affect cell behavior and tissue regeneration. However, few studies have focused on the construction of wound healing biomaterials with surface micropatterns and their role in skin tissue regeneration. In the present study, gelatin-polycaprolactone/silk fibroin composite membranes with different micropatterns were fabricated by photolithography, including line, grid and plane micropatterns. In vitro cell experiments demonstrated that the line micropattern on the composite membrane could guide cell-oriented growth, and more importantly, promote the expression of angiogenesis-related markers and α-smooth muscle actin (α-SMA) at both gene level and protein level. In the rat full-thickness skin defect model, the composite membrane with line micropatterns increased α-SMA production and neovascularization in wounds, leading to accelerated wound contraction and healing. The current study not only suggests that composite membranes with specific micropatterns can be promising wound repair materials but also provides new insights into the importance of biomaterial surface topology for tissue regeneration.

12.
BMC Microbiol ; 23(1): 4, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36604616

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) severely damages the epithelial cells of the gut lining leading to an inflamed leaky gut, translocation of microbial products, and dysbiosis resulting in systemic immune activation. Also, microbiota composition and maternal gut function can be altered in pregnancy through changes in the immune system and intestinal physiology. The aim of this study was to investigate the gut microbiota in HIV-infected and HIV-uninfected pregnant women and to compare and identify the association between gut microbial composition and adverse birth outcomes. RESULTS: A total of 94 pregnant women (35 HIV-infected and 59 HIV-uninfected controls) were recruited in Harare from 4 polyclinics serving populations with relatively poor socioeconomic status. Women were of a median age of 28 years (interquartile range, IQR: 22.3-32.0) and 55% of women were 35 weeks gestational age at enrolment (median 35.0 weeks, IQR: 32.5-37.2). Microbiota profiling in these participants showed that species richness was significantly lower in the HIV-infected pregnant women compared to their HIV-uninfected peers and significant differences in ß-diversity using Bray-Curtis dissimilarity were observed. In contrast, there was no significant difference in α-diversity between immune-compromised (CD4+ < 350 cells/µL) and immune-competent HIV-infected women (CD4+ ≥ 350 cells/µL) even after stratification by viral load suppression. HIV infection was significantly associated with a reduced abundance of Clostridium, Turicibacter, Ruminococcus, Parabacteroides, Bacteroides, Bifidobacterium, Treponema, Oscillospira, and Faecalibacterium and a higher abundance of Actinomyces, and Succinivibrio. Low infant birth weight (< 2500 g) was significantly associated with high abundances of the phylum Spirochaetes, the families Spirochaeteceae, Veillonellaceae, and the genus Treponema. CONCLUSION: The results reported here show that the species richness and taxonomy composition of the gut microbiota is altered in HIV-infected pregnant women, possibly reflecting intestinal dysbiosis. Some of these taxa were also associated with low infant birth weight.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV , Lactente , Gravidez , Humanos , Feminino , HIV , Resultado da Gravidez , Infecções por HIV/microbiologia , Peso ao Nascer , Disbiose , Zimbábue
13.
J Zhejiang Univ Sci B ; 24(1): 78-88, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36632752

RESUMO

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.


Assuntos
Diabetes Gestacional , Melatonina , Gravidez , Feminino , Humanos , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Receptor MT2 de Melatonina/genética , PPAR gama , Polimorfismo Genético , Glicemia/metabolismo , Glucose , Polimorfismo de Nucleotídeo Único
14.
J Food Sci ; 88(2): 732-743, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36624623

RESUMO

Saffron floral bio-residues (SFB) are a valuable natural source of antioxidants and dyes that can contribute to the development of new food products and cosmetic products. Color change was usually observed during SFB storage, which may result in quality degradation of SFB or even cause potential hazard to human health. In order to clarify the mechanism of color change of SFB sample, the chemical differences among SFB samples stored under different conditions were analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and chemometrics methods, from which differential flavonols and anthocyanins were screened and their kinetic variations during sample storage summarized. In addition, the color change of the SFB sample was digitalized using an electronic eye (E-eye), which was found to be related to the content of delphinidin-3,5-di-O-glucoside (DDG). Moreover, the degradation kinetic parameters of DDG under different storage conditions were studied. In conclusion, the variation of kaempferol-, isorhamnetin-, and quercetin-type flavonol, and delphinidin- and petunidin-type anthocyanin resulted in the color change of SFB sample, and anthocyanin was found more unstable than flavonol. PRACTICAL APPLICATION: Saffron floral bio-residues (SFB) are popular natural sources of antioxidants and colorants that can be used in food and cosmetic products. Color change usually occurs during SFB storage period. Clarifying the mechanism of the color change of SFB will help us to ensure the quality of SFB.

15.
Phytomedicine ; 109: 154618, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610137

RESUMO

BACKGROUND: Tumor cells reprogram their metabolic network to maintain their uncontrolled proliferation, metastasis, and resistance to cancer therapy. Treatments targeting abnormal cellular metabolism may have promising therapeutic effects. Formosanin C (FC), a diosgenin derived from the rhizoma of Paris polyphylla var. yunnanensis, has shown potent anti-cancer activities against various cancer types. However, the effect of FC on cancer metabolism remains to be elucidated. PURPOSE: In this research, we aimed to elucidate FC's effect and potential mechanisms on metabolism in lung cancer. METHODS: Colony formation, transwell cell migration, and apoptosis were detected in multiple NSCLC cell lines to assess the cytotoxicity of FC. 1H NMR metabolomics approach was applied to screen the differential metabolites in H1299 cells and the culture medium. Western blotting, flow cytometry, and other molecular biological techniques were performed to verify the latent mechanism involved in metabolites. An allograft tumor model was employed to investigate the anti-tumor effects of FC in vivo. RESULTS: FC significantly inhibited monoclonal formation and migration and induced cell cycle arrest and apoptosis in NSCLC cells. FC altered the abundances of 12 metabolites in lung cancer cells and 3 metabolites in the medium. These differential metabolites are primarily involved in glycolysis, citric acid cycle, and glutathione pathways. Notably, there was a remarkable increase in intracellular lactate and a reduction in extracellular lactate after FC treatment. Mechanically, FC downregulated the expression of MCT4 and CD147, blocking the export of lactate. Furthermore, FC also evoked mitochondrial dysfunction coupled with excessive oxidative stress, decreased mitochondrial membrane potential, ATP production reduction, glutathione depletion, and Ca2+ overload. Moreover, FC suppressed tumor progression in vivo with reduced protein levels of the MCT4 and CD147 in tumor tissues. CONCLUSION: FC inhibits lung cancer growth by the novel mechanism in which MCT4/CD147-mediated inhibition of lactate transport and disruption of mitochondrial functions are involved.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Diosgenina , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Diosgenina/farmacologia , Ácido Láctico/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Transportadores de Ácidos Monocarboxílicos/metabolismo
16.
Opt Lett ; 48(2): 407-410, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638469

RESUMO

With the extensive research on the Pancharatnam-Berry phase, metasurfaces have been widely designed as various cross-polarized nanodevices for circularly polarized (CP) illumination. However, co- and cross-polarized lights are rarely co-modulated by the metasurface. To fully utilize the transmitted light, we propose a spin-selected bifunctional metasurface composed of arrayed silver nanorods, integrating an amplitude-based grayscale imaging for co-polarized transmission and a phase-based metalens for cross-polarized transmission, under left-handed CP incidence. Moreover, such dual functionalities work well under right-handed CP incidence. Both experiments and simulations demonstrate the bifunctional performance as potential meta-devices.

17.
J Orthop Surg Res ; 18(1): 66, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707863

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of unilateral wiltse transforaminal lumbar interbody fusion (TLIF) combined with unilateral nail bar system fixation for single-level lumbar degenerative diseases with the assistance of a new automatic retraction device in a retrospective comparative study. METHODS: A total of 46 patients with single-level lumbar degenerative diseases from September 2019 to December 2021 were retrospectively analyzed. Bilateral nail bar fixation with bullet-type fusion cage (ctrl group, 24 patients) and unilateral nail bar fixation on the affected side with kidney-like fusion cage (study group, 22 patients) were performed in TLIF via wiltse intermuscular approach assisted by a new automatic retraction device. The differences in intraoperative blood loss, operative time, intraoperative fluoroscopy time, postoperative drainage, bed rest, VAS score, ODI score, JOA score, serological creatine kinase (CK), the proportion of multifidus atrophy, modified Pfirrmann classification and intervertebral space height of the upper intervertebral disc were compared between the two groups based on clinical and imaging data. RESULTS: Intraoperative bleeding, operative time, and postoperative drainage were significantly lower in study group than ctrl group, and there were no significant differences in bed rest time and intraoperative fluoroscopy time between them. In addition, there was no statistical difference in CK between the study group and the ctrl group at 24 and 48 h postoperatively. Moreover, no statistically significant difference was found in VAS score of low back pain, VAS score of lower limb pain, ODI index, modified Pfirrmann classification of the upper intervertebral disc and intervertebral space height of the upper intervertebral disc between two groups. The atrophy ratio of multifidus muscle was significantly lower in the study group. CONCLUSION: The new automatic retraction device assisted unilateral TLIF surgery with wiltse approach combined with unilateral nail bar fixation is a simple, effective and easy to master surgical method for single-level lumbar degenerative diseases.


Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Humanos , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Região Lombossacral/cirurgia , Resultado do Tratamento , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Atrofia
18.
Cancers (Basel) ; 15(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36672461

RESUMO

BACKGROUND: Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about. METHODS: This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496). RESULTS: 26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences. CONCLUSION: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.

19.
Plant Cell Environ ; 46(3): 1004-1017, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36515398

RESUMO

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in immune response in animals. However, the role of MIFs in plants such as Medicago truncatula, particularly in symbiotic nitrogen fixation, remains unclear. An investigation of M. truncatula-Sinorhizobium meliloti symbiosis revealed that MtMIF3 was mainly expressed in the nitrogen-fixing zone of the nodules. Silencing MtMIF3 using RNA interference (Ri) technology resulted in increased nodule numbers but higher levels of bacteroid degradation in the infected cells of the nitrogen-fixing zone, suggesting that premature aging was induced in MtMIF3-Ri nodules. In agreement with this conclusion, the activities of nitrogenase, superoxide dismutase and catalase were lower than those in controls, but cysteine proteinase activity was increased in nodulated roots at 28 days postinoculation. In contrast, the overexpression of MtMIF3 inhibited nodule senescence. MtMIF3 is localized in the plasma membrane, nucleus, and cytoplasm, where it interacts with methionine sulfoxide reductase B (MsrB), which is also localized in the chloroplasts of tobacco leaf cells. Taken together, these results suggest that MtMIF3 prevents premature nodule aging and protects against oxidation by interacting with MtMsrB.


Assuntos
Senilidade Prematura , Fatores Inibidores da Migração de Macrófagos , Medicago truncatula , Nódulos Radiculares de Plantas/metabolismo , Medicago truncatula/fisiologia , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , Senilidade Prematura/metabolismo , Fixação de Nitrogênio/fisiologia , Nitrogênio/metabolismo , Simbiose/fisiologia
20.
J Cancer Res Clin Oncol ; 149(1): 541-552, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36550389

RESUMO

Drug resistance and toxicity are major challenges observed during cancer treatment. In recent years, gut microbiota has been found to be strongly associated with the efficacy, toxicity, and side effects of chemotherapy, radiotherapy, and immunotherapy. Both preclinical studies and clinical trials have demonstrated the potential of microbiota modulation for cancer treatment. The human gut microbiota has exciting prospects for developing biomarkers to predict the outcome of cancer treatment. Moreover, multiple approaches can alter the gut microbiota composition, including faecal microbiota transplantation (FMT), probiotics, antibiotics (ATB), and diet. We describe the mechanisms by which the gut microbiota influences the efficacy and toxicity of cancer therapy, disease-related biomarkers, and methods to target the gut microbiota to improve outcomes. The purpose of this review is to provide new ideas for optimising cancer therapy by providing up-to-date information on the relationship between gut microbiota and cancer therapy, and hopes to find new targets for cancer treatment from human microbiota.


Assuntos
Microbioma Gastrointestinal , Microbiota , Neoplasias , Humanos , Transplante de Microbiota Fecal/métodos , Imunoterapia/métodos , Biomarcadores , Neoplasias/terapia
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