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1.
Front Bioeng Biotechnol ; 12: 1337269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895557

RESUMO

Objective: To investigate the technical feasibility of applying a simple suture guide device to close the annulus fibrosus (AF) of the intervertebral discs (IVD). Methods: 30 sheep functional discal units (FDUs) were obtained and subjected to mock discectomy. Mock sutures were performed using 3-0 non-absorbable sutures under a novel AF suture device following a suture procedure. The FDUs were compressed under axial loading at 1.8 mm/min and evaluated for Failure load (N). Results: The failure loads of the hand stitching group (Group H) and suture device stitching group (Group S) were significantly higher than those of the control group (Group C) (p = 0.033; p < 0.001). Conclusion: This study provides reasonable reasons to believe that the simple suture guide device described here is technically feasible for AF defect closure. It thus constitutes an encouraging proof of concept for the proposed device; however, it does not constitute a complete demonstration of the device's feasibility in the clinical setting considering that the annulus closure operation is performed ex vivo on functional spinal units, as opposed to within an environment that mimics the clinical setting. To this end, confirmatory experiments will be conducted such as more multiaxial or dynamic mechanical testing, and notably performing the surgery on sheep models instead of on ex vivo functional spinal units.

2.
J Mater Chem B ; 12(7): 1730-1747, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38294330

RESUMO

Spinal diseases often result in compromised mobility and diminished quality of life due to the intricate anatomy surrounding the nervous system. Medication and surgical interventions remain the primary treatment methods for spinal conditions. However, currently available medications have limited efficacy in treating spinal surgical diseases and cannot achieve a complete cure. Furthermore, surgical intervention frequently results in inevitable alterations and impairments to the initial anatomical integrity of the spinal structure, accompanied by the consequential loss of certain physiological functionalities. Changes in spine surgery treatment concepts and modalities in the last decade have led to a deepening of minimally invasive treatment, with treatment strategies focusing more on repairing and reconstructing the patient's spine and preserving physiological functions. Therefore, developing novel and more efficient treatment strategies to reduce spinal lesions and iatrogenic injuries is essential. In recent years, significant advancements in biomedical research have led to the discovery that hydrogels possess excellent biocompatibility, biodegradability, and adjustable mechanical properties. The application of hydrogel-based biotechnology in spinal surgery has demonstrated remarkable therapeutic potential. This review presents the therapeutic strategies for spinal diseases based on hydrogel tissue engineering technology.


Assuntos
Hidrogéis , Doenças da Coluna Vertebral , Humanos , Qualidade de Vida , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Neurocirúrgicos/métodos , Doenças da Coluna Vertebral/tratamento farmacológico , Doenças da Coluna Vertebral/cirurgia
3.
J Hazard Mater ; 463: 132911, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-37939564

RESUMO

Biodegradable plastics (BPs) are more prone to generate harmful microplastics (MPs) in a short time, which have always been ignored. Oxygenated functional group formation is considered to be a key indicator for assessing microplastic formation, while it is difficult to characterize at a very early stage. The micromechanical properties of the aging plastic during the formation of the MPs are highly influenced by the evolution of oxygen-containing functional groups, however, their relationship has rarely been revealed. Herein, we compared changes in the physicochemical properties of BPs and non-degradable plastic bags during aging in artificial seawater, soil, and air. The results showed that the oxidation of plastics in the air was the most significant, with the most prominent oxidation in BPs. The accumulation of carbonyl groups leads to a significant increase in the micromechanical properties and surface brittleness of the plastic, further exacerbating the formation of MPs. It was also verified by the FTIR, 2D-COS, AFM, and Raman spectroscopy analyses. Furthermore, the increased adhesion and roughness caused by oxygen-containing functional groups suggest that the environmental risks of BPs cannot be ignored. Our findings suggest that the testing of micromechanical properties can predicate the formation of the MPs at an early stage.


Assuntos
Plásticos Biodegradáveis , Microplásticos/toxicidade , Plásticos , Oxigênio , Água do Mar
4.
BMC Musculoskelet Disord ; 24(1): 939, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053117

RESUMO

BACKGROUND: Spinal subdural hematoma (SSH) is a rare cause of compression of the neutral elements of the spinal cord. However, little is known about the presentation of acute SSH after lumbar spine surgery. The reason for this may be that symptomatic SSH occurs rarely and is not given enough attention by spine surgeons. Currently, the decision to perform MRI postoperatively is more dependent on surgeon preference; therefore, no high-quality studies have been published. Our team reports our experience in the diagnosis and management of SSH after lumbar decompression and fusion surgery. METHODS: We retrospectively studied 215 patients who underwent routine MRI following minimal invasive transforaminal lumbar interbody fusion (MI-TLIF) between 2020-01-01 and 2022-06-30. The patients were divided into SSH group (17 cases) and non-SSH group (198 cases) according to the occurrence of SSH. Univariate analysis and multivariate logistic regression analysis were performed to identify relevant risk factors that increase the risk of SSH postoperatively. RESULTS: None of the patients presented with serious neurologic symptoms, such as lower extremity paralysis or cauda equina syndrome that required emergency hematoma debridement. SSH was found in 17 (7.9%) patients and non-SSH in 198 (92.1%). Factors affecting SSH were presence of hypertension, presence of diabetes and postoperative anticoagulant therapy. The significantly independent risk factor of postoperative SSH were diabetes (P = 0.008, OR: 6.988) and postoperative anticoagulant therapy (P = 0.003, OR: 8.808). CONCLUSIONS: SSH after MI-TLIF is not a rare condition, with generally no requirement of emergency evacuation. Comprehensive anti-symptomatic treatment could achieve satisfactory results. Diabetes mellitus and postoperative anticoagulant therapy are independent risk factors for SSH. Spine surgeons should hold applicability of the use of anticoagulants after lumbar surgery.


Assuntos
Diabetes Mellitus , Hematoma Subdural Espinal , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Hematoma Subdural Espinal/diagnóstico por imagem , Hematoma Subdural Espinal/etiologia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fatores de Risco , Análise Multivariada , Anticoagulantes , Resultado do Tratamento
5.
Front Bioeng Biotechnol ; 11: 1259731, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37811372

RESUMO

The intervertebral disc (IVD) is a load-bearing, avascular tissue that cushions pressure and increases flexibility in the spine. Under the influence of obesity, injury, and reduced nutrient supply, it develops pathological changes such as fibular annulus (AF) injury, disc herniation, and inflammation, eventually leading to intervertebral disc degeneration (IDD). Lower back pain (LBP) caused by IDD is a severe chronic disorder that severely affects patients' quality of life and has a substantial socioeconomic impact. Patients may consider surgical treatment after conservative treatment has failed. However, the broken AF cannot be repaired after surgery, and the incidence of re-protrusion and reoccurring pain is high, possibly leading to a degeneration of the adjacent vertebrae. Therefore, effective treatment strategies must be explored to repair and prevent IDD. This paper systematically reviews recent advances in repairing IVD, describes its advantages and shortcomings, and explores the future direction of repair technology.

6.
Front Immunol ; 14: 1195075, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37435064

RESUMO

Cancer vaccines have gained widespread attention in recent years as an emerging treatment for tumors. However, most therapeutic cancer vaccines have failed in phase III clinical trials due to faint clinical benefits. In this study, we funded that a specific synbiotic composing Lactobacillus rhamnosus GG (LGG) and jujube powder significantly enhanced the therapeutic effects of whole cells cancer vaccine in MC38 cancer cells bearing-mouse. The utilization of LGG increased the abundance of Muribaculaceae, which is conductive to an enhanced anti-tumor effect, but reduced microbial α-diversity. The use of jujube nursed probiotic microorganisms in Lachnospiaceae and enriched microbial diversity, as indicated by increased Shannon and Chao index. The reshaped gut microbiota by this synbiotic improved lipid metabolism conductive to intensified infiltration of CD8+ T cells in the tumor microenvironment and enhanced the potency of above-mentioned cancer vaccine. These encouraging findings are helpful for further efforts towards enhancing the therapeutic effects of cancer vaccines through nutritional intervention.


Assuntos
Vacinas Anticâncer , Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Neoplasias , Ziziphus , Animais , Camundongos , Linfócitos T CD8-Positivos , Pós
7.
BMC Musculoskelet Disord ; 24(1): 473, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296434

RESUMO

PURPOSE: Percutaneous vertebroplasty(PVP) has been widely used in treating symptomatic Schmorl's nodes(SNs). However, there were still some patients with poor pain relief. At present, there is a lack of research to analyze the reasons for poor efficacy. METHODS: Review the SNs patients treated with PVP in our hospital from November 2019 to June 2022, collect their baseline data. Reverse reconstruction software was used to calculate the filling rate of bone edema ring(Rf). NRS score was used to evaluate pain and ODI to evaluate function. The patients were divided into remission group(RG) and non remission group(n-RG) according to symptom. In addition, according to the Rf, they were divided into excellent, good and poor groups. Differences between groups were investigated. RESULTS: A total of 26 vertebrae were included in 24 patients. When grouped according to symptoms, patients in n-RG were older, and surgical segments were tend to locate in lower lumbar spine. The proportion of Poor distribution was significantly higher. When grouped according to the cement distribution, the preoperative NRS and ODI of the three groups were comparable, but the NRS and ODI of Poor group were significantly worse than the Excellent and Good groups postoperatively and at the last follow-up. CONCLUSIONS: The cement distribution may significantly affect the efficacy of PVP in treating symptomatic SNs. We suggest that the bone edema ring should be filled as fully as possible to ensure the efficacy. In addition, advanced age and low lumbar lesions are also adverse factors for clinical outcomes.


Assuntos
Fraturas por Compressão , Deslocamento do Disco Intervertebral , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Cimentos Ósseos/uso terapêutico , Resultado do Tratamento , Deslocamento do Disco Intervertebral/diagnóstico , Dor , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos
8.
Regen Biomater ; 10: rbad040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250976

RESUMO

Polymethylmethacrylate (PMMA) bone cement extensively utilized for the treatment of osteoporotic vertebral compression fractures due to its exceptional handleability and mechanical properties. Nevertheless, the clinical application of PMMA bone cement is restricted by its poor bioactivity and excessively high modulus of elasticity. Herein, mineralized small intestinal submucosa (mSIS) was incorporated into PMMA to prepare a partially degradable bone cement (mSIS-PMMA) that provided suitable compressive strength and reduced elastic modulus compared to pure PMMA. The ability of mSIS-PMMA bone cement to promote the attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells was shown through cellular experiments carried out in vitro, and an animal osteoporosis model validated its potential to improve osseointegration. Considering these benefits, mSIS-PMMA bone cement shows promising potential as an injectable biomaterial for orthopedic procedures that require bone augmentation.

9.
Nutrients ; 15(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37111173

RESUMO

Whereas vaccination is established as one of the most effective and available methods against seasonal flu and holds high potential for many infectious diseases, immune response may differ among individuals and regions. In this study we examined the effects of gut microbiota on vaccination with human serum albumin (HSA) as the model vaccine in C57BL/6J mice. We observed that a two-week antibiotic cocktail (ABX) treatment hampered HSA-specific IgG1 in serum, whereas fecal microbiota transplantation (FMT) restored the gut microbiota impaired by the ABX treatment and consequently increased the proportions of macrophages in the mesenteric lymph nodes (MLNs), plasma cells in the peripheral blood, and HSA-specific immunoglobulin G1 (IgG1) in the serum. A week of daily application of jujube powder (800 mg/kg) to ABX-treated mice achieved a significantly higher HSA-specific IgG1 concentration in the serum compared with the ABX treatment group. Of particular note was that the administration of the jujube powder did not increase the myeloid cells, indicating a different mechanism of vaccination compared with FMT. More interestingly, daily pre-administration of jujube powder (800 mg/kg) to healthy mice one week ahead of vaccination boosted their immune response, as evidenced by the proportion of macrophages in the MLNs, B cells in the spleen, plasma cells and memory B cells in the peripheral blood, and HSA-specific IgG1 concentration in the serum. The 16S rRNA sequencing of gut microbiota revealed that the administration of jujube powder increased the abundance of Coriobacteriaceae associated with the metabolism of amino acids. The Kyoto encyclopedia of genes and genomes (KEGG) analysis suggested the altered microbiota is more favorable for arginine and proline metabolism, which may promote macrophages in the MLNs. These results indicate a high potential for boosting vaccination by manipulating gut microbiota with natural products.


Assuntos
Microbioma Gastrointestinal , Ziziphus , Humanos , Animais , Camundongos , Pós , Albumina Sérica Humana , RNA Ribossômico 16S/genética , Camundongos Endogâmicos C57BL , Imunoglobulina G , Vacinação , Arginina/farmacologia
10.
Phys Chem Chem Phys ; 24(36): 22028-22037, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36069567

RESUMO

Perennial interest in enzyme catalysis has been expanding its applicability from aqueous phases where enzymes are naturally evolved to organic solvents in which the majority of industrial chemical syntheses are carried out. Although conjugating an enzyme with a soluble polymer has been attempted to enhance enzyme activity in organic solvents, the underlying mechanism remains poorly understood in terms of the conformational dynamics and enzyme activity. Herein, we combine LF-NMR measurements and MD simulations to investigate the effects of polymer grafting on the conformational dynamics of CalB in organic solvents and the consequential impacts on the catalytic kinetics, using the lipase-catalyzed transesterification reaction as a model system. LF-NMR measurements confirm that conjugation with a soluble polymer improves the enzyme flexibility in organic solvents, leading to an increase in the catalytic efficiency of up to two orders of magnitude. MD simulations suggest that the conjugated enzyme samples a larger conformational space, compared to its native counterpart, validating the hypothesis that polymer motion enhances enzyme dynamics. These experimental and simulation results provide new insights for enhancing enzyme conformational dynamics and thereby catalytic kinetics in organic solvents.


Assuntos
Lipase , Polímeros , Catálise , Domínio Catalítico , Esterificação , Lipase/química , Solventes/química
11.
Front Immunol ; 13: 826597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967357

RESUMO

While recent years have witnessed ever-growing evidence on the prebiotic attributes of anthocyanins for treatment of microbiota-associated diseases, the complex interplay between anthocyanin uptake, the gut microbiota, and the intestinal mucosal immune system remains poorly understood. Here, we investigate the effects of bilberry anthocyanins on the gut microbiota composition and metabolism, and the intestinal mucosal immune system of mice. We observed an increased proportion of IgA-producing plasma cells in the mesenteric lymph nodes (MLNs) and an enhanced secretion of secretory immunoglobulin A (sIgA) and antimicrobial peptides in the small intestine. Small intestine transcriptome analysis further suggested that anthocyanins influenced IgA production. We found that oral administration of anthocyanins altered the gut microbiota through maintaining the anaerobic intestinal environment, promoting the secretion of sIgA and antimicrobial peptides, and downregulating cell motility and mobile genetic elements of commensal bacteria. These observations suggest that the oral administration of anthocyanins helps in maintaining intestinal homeostasis and thus it may find applications in immunotherapy and related fields.


Assuntos
Antocianinas , Intestinos , Administração Oral , Animais , Antocianinas/metabolismo , Antocianinas/farmacologia , Imunoglobulina A Secretora , Mucosa Intestinal , Camundongos
12.
J Immunol Res ; 2022: 9202491, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903754

RESUMO

Colitis is a frequently occurred side effect of immune checkpoint inhibitors (ICIs), which are increasingly used in cancer treatment, whereas antibiotics are widely used to treat colitis, their effectiveness in ICI-associated colitis remains controversial. In this study, we firstly assessed the effectiveness of several commonly used antibiotics and antibiotic cocktails in alleviating of dextran sulfate sodium- (DSS-) induced colitis. We observed that two narrow-spectrum antibiotics, neomycin and metronidazole, were more effective in alleviating colitis, as evidenced by the remission of loss of the body weight, enlargement of the spleen, shortening of the colon, secretion of proinflammatory cytokines, and histological score of the colon tissue. Moreover, these two antibiotics resulted in better relief of colitis symptoms in the MC38 tumor-bearing male mice receiving the anti-PD-L1 mAb (αPD-L1) treatment, compared to the females. In the meantime, an enhanced response to αPD-L1 efficiency against mice colon cancer was observed in the male mouse group upon the application of these two antibiotics. In contrast, both neomycin and metronidazole showed destructive effects on the antitumor efficiency of αPD-L1 in female mice, despite relief from colitis. We found that antibiotic treatment attenuated the increased infiltration of granulocytes and myeloid cells in colon tissue induced by DSS in female mice, while reducing the proportion of Th17 cells in male mice. These differences were further associated with the sex-biased differences in the gut microbiota. These findings indicated that sex-dependent alterations in the gut microbiota should be considered when applying antibiotics for the treatment of ICI-associated colitis.


Assuntos
Colite , Neoplasias do Colo , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Citocinas , Modelos Animais de Doenças , Feminino , Imunidade , Masculino , Metronidazol/efeitos adversos , Camundongos , Neomicina/farmacologia , Neomicina/uso terapêutico
13.
J Oncol ; 2022: 3909030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685428

RESUMO

Background: Glioblastoma (GBM) is the most malignant of all known intracranial tumors; meanwhile, most patients have a poor prognosis. In order to improve the poor prognosis of GBM patients as much as possible, it is specifically significant to identify biomarkers related to the gene diagnosis and gene therapy. Methods: In this study, a total of 343 GBM specimens and 259 nontumor specimens were collected from four Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database; then, we analyzed the differentially expressed genes (DEGs) from the above data. Through Venn diagram analysis, 54 common upregulated DEGs and 22 common downregulated DEGs were triumphantly recognized. Results: On the basis of the degree of formation communication in protein-protein interaction network (PPIN), the 10 upregulated central genes were ranked, incorporating LOX, IGFBP3, CD44, TIMP1, FN1, VEGFA, POSTN, COL1A1, COL1A2, and COL3A1. By combining the expression levels and the clinical features of GBM, we found that four hub genes (TIMP1, FN1, POSTN, and LOX) were significantly upregulated and related to poor prognosis of GBM. Meanwhile, univariate and multivariate Cox regression analysis suggested that TIMP1 could be one of the independent prognostic factors for GBM patients. Furthermore, TIMP1 was particularly correlated with the immune marker of macrophage M1, macrophage M2, neutrophils, tumor-associated macrophage, and Tregs. We then analyzed the role of TIMP1 in GBM cancer cell lines by relevant experiments, which indicated that TIMP1 knockdown resulted in the decreased cell proliferation, migration, and invasion. Conclusions: Taken together, these findings demonstrated that TIMP1 might be a new biomarker to determine prognosis and immune infiltration of GBM patients.

14.
ACS Synth Biol ; 11(7): 2361-2371, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35772024

RESUMO

Mitigating unintended interferences between circuits and host cells is key to realize applications of synthetic regulatory systems both for bacteria and mammalian cells. Here, we demonstrated that growth burden and circuit dysregulation occurred in a concentration-dependent manner for specific transcription factors (CymR*/CymR) in E.coli, and direct negative feedback modules were able to control the concentration of CymR*/CymR, mitigate growth burden, and restore circuit functions. A quantitative design scheme was developed for circuits embedded with autorepression modules. Four key parameters were theoretically identified to determine the performance of autoregulated switches and were experimentally modified by fine-tuning promoter architectures and cooperativity. Using this strategy, we synthesized a number of switches and demonstrated its improvement of product titers and host growth controlling the complex deoxyviolacein biosynthesis pathway. Furthermore, we restored functions of a dysregulated multilayer NOR gate by integrating autorepression modules. Our work provides a blueprint for engineering host-adaptable synthetic systems.


Assuntos
Escherichia coli , Redes Reguladoras de Genes , Escherichia coli/genética , Redes Reguladoras de Genes/genética , Engenharia Genética , Regiões Promotoras Genéticas/genética , Biologia Sintética , Fatores de Transcrição/genética
15.
Comput Methods Biomech Biomed Engin ; 25(15): 1744-1756, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35230207

RESUMO

Percutaneous vertebral augmentation (PVA) and percutaneous cement discoplasty (PCD) are two relatively new minimally invasive surgeries for symptomatic Schmorl's reported in recent decade. However, the clinical evidence for the effectiveness of these two surgeries is insufficient. The purpose of this study was to compare the biomechanical benefits and risks of the two surgeries in order to analyze their biomechanical differences and effectiveness. We reconstructed Five lumbar finite element models via computed tomography data, including control model, PVA-ideal model, PVA-nonideal model, PCD-ideal model, and PCD-nonideal model. The stress and strain of Schmorl's nodes, bone marrow edema zone (BMEZ), affected endplate, and the overall stability of segment were analyzed and compared. The validity of our models was confirmed. As a result, the PVA-ideal model can significantly reduce the stress of Schmorl's node and the strain of BMEZ, while this effect is inappreciable in PVA-nonideal model. The PCD-ideal model significantly reduced the strain of Schmorl's nodes and BMEZ, and significantly improve segmental stability, but also resulted in a significant increase in the stress of Schmorl's nodes, BMEZ and endplates. The PCD-nonideal model not only lacks blocking effect, but also sharply increases the strain of Schmorl's nodes and BMEZ. Thus, We recommend that both PVA and PCD surgeries in ideal distribution facilitated a more stable paranodular biomechanical microenvironment. However, due to the possibility of poor biomechanical outcomes caused by the non-ideal cement distribution, the non-ideal distribution of bone cement needs to be remedied in practice.


Assuntos
Cimentos Ósseos , Deslocamento do Disco Intervertebral , Humanos , Análise de Elementos Finitos , Cimentos Ósseos/uso terapêutico , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios X , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia
16.
Oncoimmunology ; 10(1): 1981570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595060

RESUMO

Low response rates to certain tumor types remain a major challenge for immune checkpoint blockade therapy. In this study, we first conducted an integrated biomarker evaluation of bladder cancer patients from confirmatory cohorts (IMvigor210) and found that no significant differences exist between sexes before acceptance of anti-PD-L1 treatment, whereas male patients showed a better response. Thus, we then focused on sex-related changes post anti-PD-L1 treatment and found no obvious impact on the gut microbiota in male mice but a significant decrease in the sex hormone levels. Further, castration dramatically enhanced the antitumor efficacy against murine colon adenocarcinoma in male mice. Moreover, a narrow-spectrum antibiotic, colistin was innovatively used for deregulation of testosterone levels to enhance the immunotherapy efficiency in male mice. These findings indicate that the impact on the sex hormone levels in males may contribute to the sexual dimorphism in response and provide a promising way to enhance immunotherapy efficiency.


Assuntos
Imunoterapia , Neoplasias da Bexiga Urinária , Animais , Humanos , Fatores Imunológicos , Masculino , Camundongos , Testosterona , Neoplasias da Bexiga Urinária/tratamento farmacológico
17.
Nutrients ; 13(8)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34444860

RESUMO

Cyclophosphamide (CTX) is widely applied in cancer treatment. However, the outcome is often compromised by lymphopenia, myelosuppression, and gut dysbiosis. Here, we used jujube powder to enhance CTX efficiency through nurturing gut microbiota in order to facilitate favorable metabolisms. It was observed that the oral administration of jujube powder enriched CD8+ T cells in mouse MC38 colon tumor microenvironment and increased the diversity of gut microbiota and the abundance of Bifidobacteriales, which is helpful to the production of butyrate in the cecum content. The application of jujube powder also stimulated the production of white blood cells, especially CD8+ T cells in peripheral and bone marrow, while inhibiting the growth of eosinophils in peripheral blood and the production of IL-7 and GM-CSF in serum. All these are conductive to the significant inhibition of the tumor growth, suggesting the high potential of nurturing gut microbiota with natural products for improving the efficiency of chemotherapy.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Ciclofosfamida/farmacologia , Frutas , Ziziphus , Animais , Medula Óssea/metabolismo , Terapia Combinada , Modelos Animais de Doenças , Eosinofilia , Microbioma Gastrointestinal/efeitos dos fármacos , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Camundongos , Pós , Microambiente Tumoral/efeitos dos fármacos
18.
Cancers (Basel) ; 13(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34439144

RESUMO

Whereas dietary intervention with natural nutrients plays an important role in activating the immune response and holds unprecedented application potential, the underpinning mechanism is poorly understood. The present work was dedicated to comprehensively examine the effects of ultrafine jujube powder (JP) on the gut microbiota and, consequentially, the effects associated with the response rate to anti-PD-L1 treatment against murine colon adenocarcinoma. A murine colon adenocarcinoma model with anti-PD-L1 immunotherapy was established to evaluate how dietary interventions affect the microbiota. In vitro and in vivo experiments confirmed the role of SCFAs in the immune response. Oral administration of JP greatly improves the response of anti-PD-L1 treatment against murine colon adenocarcinoma. Such an improvement is associated with the alteration of gut microbiota which leads to an increased abundance of Clostridiales, including Ruminococcaceae and Lachnospiraceae, an elevated SCFA production, and an intensified infiltration of CD8+ T cells to the tumor microenvironment. This work demonstrates that JP is particularly effective in modulating the gut microbiota for an improved immune checkpoint blockage therapy by boosting cytotoxic CD8+ T cells in tumor-infiltrating lymphocytes. The experimental findings of the present study are helpful for the development of dietary intervention methods for cancer immunotherapy using natural nutrients.

19.
J Orthop Surg Res ; 16(1): 429, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217340

RESUMO

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To investigate the radiological and clinical outcomes of patients with or without pedicle-screw rod fixation (PSRF) in OLIF surgery. METHODS: Between June 2017 and December 2019, 66 consecutive patients who underwent OLIF surgery at two centers were divided into stand-alone and combined groups according to whether or not PSRF was used. Imaging and clinical data were collected preoperatively, postoperatively, 3 and 6 months postoperatively, and at the last follow-up. Related coefficient and multiple linear regression analysis was used to detect the influencing factors of cage subsidence (CS). RESULTS: There was a lower baseline BMD in the combined group (p = 0.005). The combined group showed superior VAS score at 3 months postoperatively, although there was no difference in long-term VAS and ODI scores between the two groups. The foraminal height (FH) of the two groups was comparable at preoperatively, postoperatively, and 3 months postoperatively, but the combined group showed better maintenance of FH at 6 months postoperatively (p = 0.049) and last follow-up (p = 0.019). The total CS (tCS) of the combined group was lower than that of the stand-alone group during the whole follow-up period (all p ≤ 0.001). Multiple linear regression suggested that lower BMD was the risk factor for main CS, and PSRF could significantly reduce the BMD threshold for severe CS (-4.77 vs -1.38). CONCLUSIONS: OLIF combined with PSRF can effectively avoid foraminal height loss and prevent severe CS, which may be more suitable for patients with osteoporosis or osteopenia and improve clinical outcomes.


Assuntos
Vértebras Lombares/cirurgia , Osteoporose/cirurgia , Parafusos Pediculares , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Densidade Óssea , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
20.
J Hazard Mater ; 418: 126333, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34118537

RESUMO

Carbon-bridge-modified malonamide (MLD)/g-C3N4 (CN) was prepared by copolymerization of MLD with urea and melamine and loaded with Fe3O4 for the high-efficiency removal of tetracycline (TC) in water under photo-Fenton. The prepared catalysts were characterized by SEM, TEM, N2 adsorption-desorption analysis, XPS, XRD, and FTIR, which proved that the modification method successfully introduced the C bridge into the carbon nitride molecular system and increased the structural defects of the catalyst. The Carbon-bridge-modified MLD/CN/Fe3O4 also had good visible-light response and charge-separation and transport abilities in the photoelectrochemical test. Degradation results showed that the photo-Fenton degradation of TC reached 95.8%, and the mineralization rate was 55.7% within 80 min at 80 mM H2O2 dosage, 0.5 g/L catalyst dosage, and near-neutral pH by 0.8MLD/CN/Fe3O4. Moreover, the oxidation products and mineralization pathways of TC were explored by LC-MS. Toxicity analysis indicated low environmental threat of the intermediates in TC mineralization. EPR analysis and H2O2 decomposition efficiency analyses showed an improvement in the H2O2 decomposition performance of 0.8MLD/CN/Fe3O4. This work could provide a valuable insight for the application of heterogeneous photo-Fenton technology in wastewater treatment.


Assuntos
Carbono , Poluentes Químicos da Água , Catálise , Peróxido de Hidrogênio , Fenômenos Magnéticos , Tetraciclina , Poluentes Químicos da Água/análise
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