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1.
Front Oncol ; 14: 1380725, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39188687

RESUMEN

Objective: The present study aimed to compare the effectiveness and reliability of quantified superb microvascular imaging (qSMI) and quantified contrast-enhanced ultrasonography (qCEUS) in assessing vascularization in both operable and non-operable uterine cervical cancer. Methods: A case-control study included 64 patients with pathology-proven and untreated cervical cancer, who underwent transvaginal ultrasonography combined with qSMI and qCEUS between January 2022 and June 2023. SMI results were quantified as the vascular index (VI), which were compared to 12 quantitative parameters of CEUS calculated with time-intensity curves (TIC). Results: According to FIGO staging and different treatment regimens, 64 patients with cervical cancer were divided into operable group (IA ~ IIA, n = 19) and non-operable group (IIB ~ IV, n = 45). In comparison to the operable group, the non-operable group showed significantly higher values in VI, peak intensity (PI), area under the curve (AUC), wash-in area (iAUC), wash-out area (oAUC), wash-in rate (WiR), mean intensity (Mean Int), and standard deviation (STD) (all P < 0.05). VI demonstrated strong correlations with CEUS parameters, notably PI (r = 0.854, P < 0.001) and AUC (r = 0.635, P < 0.001). Furthermore, VI showed a better predictive performance for treatment-group assignment than qCEUS parameters, with an 80.7% accuracy, 64.4% sensitivity and 89.5% specificity. Conclusion: Both qSMI and qCEUS exhibit significant and comparable utility in detecting microvascular hyperplasia and predicting treatment-group assignments in cervical cancer. Furthermore, qSMI may offer added convenience in implementation.

2.
Front Mol Biosci ; 11: 1419093, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006969

RESUMEN

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Small extracellular vesicles (sEVs) are bilayer lipid membrane vesicles containing RNA that exhibit promising diagnostic and prognostic potential as cancer biomarkers. Aims: To establish a miRNA panel from peripheral blood for use as a noninvasive biomarker for the diagnosis of HCC. Methods: sEVs obtained from plasma were profiled using high-throughput sequencing. The identified differential miRNA expression patterns were subsequently validated using quantitative real-time polymerase chain reaction analysis. Results: The random forest method identified ten distinct miRNAs distinguishing HCC plasma from non-HCC plasma. During validation, miR-140-3p (p = 0.0001) and miR-3200-3p (p = 0.0017) exhibited significant downregulation. Enrichment analysis uncovered a notable correlation between the target genes of these miRNAs and cancer development. Utilizing logistic regression, we developed a diagnostic model incorporating these validated miRNAs. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.951, with a sensitivity of 90.1% and specificity of 87.8%. Conclusion: These aberrantly expressed miRNAs delivered by sEVs potentially contribute to HCC pathology and may serve as diagnostic biomarkers for HCC.

3.
Int J Pharm ; 660: 124344, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38885779

RESUMEN

The enhancement of conventional liposome and lipid nanoparticle (LNP) methodologies in the formulation and deployment of messenger RNA (mRNA) vaccines necessitates further refinement to augment both their effectiveness and biosafety profiles. Additionally, researching these innovative delivery carrier materials represents both a prominent focus and a significant challenge in the current scientific landscape. Here we designed new chiral self-assembling peptides as the delivery carrier for RNA vaccines to study the underlying mechanisms in the feline infectious peritonitis virus (FIPV) model system. Firstly, we successfully transcribed mature enhanced green fluorescent protein (EGFP) mRNA and feline infectious peritonitis virus nucleocapsid (FIPV N) mRNA in vitro from optimized vectors. Subsequently, we developed chiral self-assembling peptide-1 (CSP-1) and chiral self-assembling peptide-2 (CSP-2) peptides, taking into account the physical and chemical characteristics of nucleic acid molecules as well as the principles of self-assembling peptides, with the aim of improving the delivery efficiency of mRNA molecule complexes. We determined the optimal coating ratio between CSP and mRNA by electrophoretic mobility shift assay. We found that the peptides and mRNA complexes can protect the mRNA from RNase A enzyme and efficiently deliver mRNA into cells for target antigen proteins expression. Animal experiments confirmed that CSP-1/mRNA complex can effectively trigger immune response mechanisms involving IFN-γ and T cell activation. It can also stimulate CD4+ and CD8+ T cell proliferation and induce serum antibody titers up to 10,000 times higher. And no pathological changes were observed by immunohistochemistry in liver, spleen, and kidney, indicating that CSP-1 may be a safe and promising delivery system for mRNA vaccines. Methodologically, this research represents a novel endeavor in the utilization of chiral self-assembling peptides within the realm of mRNA vaccines. This approach not only introduces fresh prospects for employing such nanomaterials in various mRNA vaccines but also expands the potential for developing small molecules, proteins, and antibodies. Furthermore, it paves the way for new clinical applications of existing pharmaceuticals.


Asunto(s)
Péptidos , ARN Mensajero , Animales , Péptidos/química , ARN Mensajero/administración & dosificación , Vacunas de ARNm , Proteínas Fluorescentes Verdes/genética , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunología , Ratones , Femenino , Gatos , Sistemas de Liberación de Medicamentos/métodos
5.
Gland Surg ; 13(1): 108-116, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38323234

RESUMEN

Percutaneous ethanol injection (PEI) is a widely used treatment option for cystic and predominantly cystic thyroid nodules. It has several advantages over other treatment modalities. Compared to surgery, PEI is less painful, can be performed in the outpatient setting, and carries less risk of transient or permanent side effects. Compared to other minimally invasive techniques such as radiofrequency ablation (RFA), PEI is less expensive and does not require specialized equipment. PEI performs well in the context of cystic nodules. PEI does not perform as well as other techniques in solid nodules, so its use as a primary treatment is limited to cystic and predominantly cystic thyroid nodules. However, PEI is also being explored as an adjunct treatment to improve ablation of solid nodules with other techniques. Here, we provide a clinical review discussing the genesis, mechanism of action, and patient selection with respect to ethanol ablation, as well as the procedure itself. Predictors of operative success, failure, and common adverse events are also summarized. Altogether, PEI allows impressive volume reduction rates with minimal complications. Several recent studies have also evaluated the long-term impact of PEI up to 10 years after treatment and revealed maintenance of robust treatment efficacy with no undesirable long-term sequelae. Thus, PEI remains the treatment of choice for benign but symptomatic cystic and predominantly cystic thyroid nodules.

6.
Front Pharmacol ; 15: 1350063, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38384292

RESUMEN

Background: Hyaluronic acid (HA), the main component of the extracellular matrix, has the ability to promote tissue repair and regulate inflammation. It is used in otolaryngology as an adjuvant treatment to alleviate postoperative nasal symptoms. However, there is currently insufficient evidence demonstrating the therapeutic efficacy of HA for patients with nasal inflammatory diseases (NIDs). Therefore, this study aimed to evaluate the efficacy and safety of topical HA in the treatment of NID patients without receiving surgery. Methods: In this meta-analysis, comprehensive searches were conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science. Keywords searched included "hyaluronic acid," "sinusitis," "allergic rhinitis," "rhinitis," and "randomized controlled trials (RCTs)." The Cochrane Collaboration's "Risk of Bias Assessment" tool was used to assess the quality of the included trials, and the meta-analysis was performed using the RevMan 5.3 and STATA 15 statistical software. Results: A total of 11 articles and 825 participants were enrolled. For the primary outcomes, the pooled results revealed that HA significantly improves nasal obstruction (SMD, -0.53; 95% CI, -0.92 to -0.14; p = 0.008; and I2 = 79%) and rhinorrhea (SMD, -0.71; 95% CI, -1.27 to -0.15; p = 0.01; and I2 = 90%) in patients with NIDs. As for the secondary outcomes, the pooled results demonstrated that when compared with the control group, HA could significantly improve nasal endoscopic scores (p < 0.05), rhinitis scores (p < 0.05), rhinomanometry (p < 0.05), nasal neutrophils (p < 0.05), and mucociliary clearance (p < 0.05). However, no significant differences were observed between the two groups regarding nasal itching, sneezing, hyposmia, quality-of-life scores, and nasal eosinophils. For the risk of bias, 54.5% and 45.5% of trials had a low risk of bias in the randomization process and deviation of the intended intervention, respectively. Conclusion: In the present study, the results reveal that HA might ameliorate symptoms of patients with NIDs. However, more clinical trials with larger participant cohorts are required to confirm this result. Systematic review registration number: clinicaltrials.gov, identifier CRD42023414539.

7.
Biochem Biophys Res Commun ; 704: 149701, 2024 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-38408415

RESUMEN

Human bronchial epithelial cells in the airway system, as the primary barrier between humans and the surrounding environment, assume a crucial function in orchestrating the processes of airway inflammation. Target to develop a new three-dimensional (3D) inflammatory model to airway system, and here we report a strategy by using self-assembling D-form peptide to cover the process. By testing physicochemical properties and biocompatibility of Sciobio-Ⅲ, we confirmed that it can rapidly self-assembles under the trigger of ions to form a 3D nanonetwork-like scaffold, which supports 3D cell culture including the cell strains like BEAS-2B cells. Subsequently, inflammation model was established by lipopolysaccharide (LPS), the expression of some markers of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-8 (IL-8), the levels of relevant inflammatory factors were measured by RT-qPCR and the secretion profile of inflammatory cytokines by ELISA, are obtained the quite difference effects in 2D and 3D microenvironment, which suggested Sciobio-Ⅲ hydrogel is an ideal scaffold that create the microenvironment for 3D cell culture. Here we are success to establish a 3D inflammation model for airway system. This innovative model allows for rapid and accurate evaluation of drug metabolism and toxicological side effects, hope to use in drug screening for airway inflammatory diseases and beyond.


Asunto(s)
Bronquios , Inflamación , Humanos , Inflamación/metabolismo , Células Cultivadas , Interleucina-1beta/metabolismo , Células Epiteliales/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
8.
Biomacromolecules ; 25(3): 1408-1428, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38236703

RESUMEN

The efficacy of the dendritic cell (DC) has failed to meet expectations thus far, and crucial problems such as the immature state of DCs, low targeting efficiency, insufficient number of dendritic cells, and microenvironment are still the current focus. To address these problems, we developed two self-assembling peptides, RLDI and RQDT, that mimic extracellular matrix (ECM). These peptides can be self-assembled into highly ordered three-dimensional nanofiber scaffold structures, where RLDI can form gelation immediately. In addition, we found that RLDI and RQDT enhance the biological function of DCs, including releasing antigens sustainably, adhering to DCs, promoting the maturation of DCs, and increasing the ability of DC antigen presentation. Moreover, peptide hydrogel-based DC treatment significantly achieved prophylactic and treatment effects on colon cancer. These results have certain implications for the design of new broad-spectrum vaccines in the future.


Asunto(s)
Células Dendríticas , Hidrogeles , Hidrogeles/farmacología , Inmunidad Celular , Péptidos/farmacología , Péptidos/química , Linfocitos T
9.
Int J Nanomedicine ; 19: 743-758, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38283199

RESUMEN

Background: The morbidity and mortality of triple-negative breast cancer (TNBC) are still high, causing a heavy medical burden. CCL5, as a chemokine, can be involved in altering the composition of the tumor microenvironment (TME) as well as the immunosuppressive degree, and has become a very promising target for the treatment of TNBC. Dysregulation of microRNAs (miRNAs) in tumor tissues is closely related to tumor progression, and its utilization can be used to achieve therapeutic purposes. Engineered exosomes can avoid the shortcomings of miRNAs and also enhance their targeting and anti-tumor effects through engineering. Therefore, we aimed to create a cRGD-modified exosome for targeted delivery of miR-588 and to investigate its effect in remodeling immunosuppressive TME by anchoring CCL5 in TNBC. Methods: In this study, we loaded miR-588 into exosomes using electroporation and modified it with cRGD using post insertion to obtain cRGD-Exos/miR-588. Transmission electron microscopy (TEM), nanoparticle tracking assay technique (NTA), Western Blots, qPCR, and flow cytometry were applied for its characterization. CCK-8, qPCR and enzyme-linked immunosorbent assay (ELISA), in vivo fluorescence imaging system, immunohistochemistry and H&E staining were used to explore the efficacy as well as the mechanism at the cellular level as well as in subcutaneous graft-tumor nude mouse model. Results: The cRGD-Exos/miR-588 was successfully constructed and had strong TNBC tumor targeting in vitro and in vivo. Meanwhile, it has significant efficacy on TME components affected by CCL5 and the degree of immunosuppression, which can effectively control TNBC with good safety. Conclusion: In this experiment, cRGD-Exos/miR-588 was prepared to remodel immunosuppressive TME by anchoring CCL5, which is affected by the vicious cycle of immune escape. Overall, cRGD-Exos/miR-588 explored the feasibility of targeting TME for the TNBC treatment, and provided a competitive delivery system for the engineered exosomes to deliver miRNAs for antitumor therapy drug.


Asunto(s)
Antineoplásicos , Exosomas , MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/patología , MicroARNs/genética , Antineoplásicos/farmacología , Inmunosupresores/farmacología , Línea Celular Tumoral , Microambiente Tumoral
10.
Esophagus ; 21(2): 141-149, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38133841

RESUMEN

BACKGROUND: Recurrent laryngeal nerve injury (RLNI) leading to vocal cord paralysis (VCP) is a significant complication following minimally invasive esophagectomy (MIE) with upper mediastinal lymphadenectomy. Transcutaneous laryngeal ultrasonography (TLUSG) has emerged as a non-invasive alternative to endoscopic examination for evaluating vocal cord function. Our study aimed to assess the diagnostic value of TLUSG in detecting RLNI by evaluating vocal cord movement after MIE. METHODS: This retrospective study examined 96 patients with esophageal cancer who underwent MIE between January 2021 and December 2022, using both TLUSG and endoscopy. RESULTS: VCP was observed in 36 out of 96 patients (37.5%). The incidence of RLNI was significantly higher on the left side than the right (29.2% vs. 5.2%, P < 0.001). Postoperative TLUSG showed a sensitivity and specificity of 88.5% (31/35) and 86.5% (45/52), respectively, with an AUC of 0.869 (P < 0.001, 95% CI 0.787-0.952). The percentage agreement between TLUSG and endoscopy in assessing VCP was 87.4% (κ = 0.743). CONCLUSIONS: TLUSG is a highly effective screening tool for VCP, given its high sensitivity and specificity. This can potentially eliminate the need for unnecessary endoscopies in about 80% of patients who have undergone MIE.


Asunto(s)
Traumatismos del Nervio Laríngeo Recurrente , Parálisis de los Pliegues Vocales , Humanos , Estudios Retrospectivos , Traumatismos del Nervio Laríngeo Recurrente/diagnóstico , Traumatismos del Nervio Laríngeo Recurrente/epidemiología , Traumatismos del Nervio Laríngeo Recurrente/etiología , Esofagectomía/efectos adversos , Laringoscopía/efectos adversos , Parálisis de los Pliegues Vocales/epidemiología , Parálisis de los Pliegues Vocales/etiología , Ultrasonografía/efectos adversos
11.
Head Neck ; 46(1): 57-63, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37872858

RESUMEN

BACKGROUND: The risk of complication in patients undergoing completion thyroidectomy (cT) is mixed. Several studies report increased risk in comparison to total thyroidectomy (TT) and still others reporting a comparatively decreased risk. We compared the rates of complication in patients at our institution undergoing thyroid lobectomy (TL), (TT), and cT by a single high-volume surgeon. METHODS: We performed a single-institution retrospective cohort study. Patients undergoing TL, TT, or cT by a high-volume surgeon were included. Rates of complication were collected and compared between the three cohorts. RESULTS: A total of 310 patients were included. The overall rate of complication was 4.2%. The complication rates in the TL, TT, and cT cohorts were 1%, 7.1%, and 4.5%, respectively (p = 0.10). Transient hypocalcemia was slightly more common in the TT cohort (6.1%) as opposed to the TL (0%) or cT (0.9%) cohort (p = 0.01). The cohorts also had similar rates of recurrent laryngeal nerve signal loss leading to transient dysphonia (TL: 0% vs. TT: 1% vs. cT: 3.6%, p = 0.10). CONCLUSIONS: While rates of complication tended to predictably decrease as approaches became less extensive, there were no significant differences in complication rates among the three surgical approaches when performed by a high-volume surgeon. Considering the low rates of complication overall, patient counseling and preference should be emphasized to provide appropriate and tailored treatment plans.


Asunto(s)
Disfonía , Neoplasias de la Tiroides , Humanos , Estudios Retrospectivos , Tiroidectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Disfonía/etiología , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/etiología
12.
Front Oncol ; 13: 1250842, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37692857

RESUMEN

Objective: The purpose of this study was to assess the diagnostic efficacy of the vascular index (VI) on superb microvascular imaging (SMI) in distinguishing normal uterine cervical epithelium, high-grade cervical intraepithelial neoplasia (CIN), and cervical cancer. Methods: The retrospective study included women with pathology-confirmed CIN or cervical cancer, who underwent transvaginal ultrasound and SMI between April 2021 and October 2022. The SIM manifestations of normal cervix and cervical lesions were reviewed. SIM were measured and converted into vascular index (VI) which compared between cervical lesions and control groups. We have retrospectively compared ultrasound features of cervical lesions and characteristics of patients. Measurement reliability was evaluated by intra class correlation coefficient (ICC). Results: A total of 235 consecutive females were enrolled, comprising 38 with high-grade CIN, 96 with cervical cancer, and 101 with a normal uterine cervix. The microvascular architecture exhibited significant variations between premalignant and malignant cervical lesions. Branch-like patterns were predominantly observed in high-grade CIN, while crab claw-like and fireball-like patterns were more commonly associated with cervical cancer. The median VI of cervical cancer (34.7 ± 10.3) was significantly higher than that of high-grade CIN (17.6 ± 4.2) (P < 0.001). Moreover, the VI values of cervical cancer differed significantly among different FIGO stages and pathological types (P < 0.001 and P = 0.003, respectively). The VI demonstrated superior diagnostic performance for cervical lesions compared to vascular patterns (AUC = 0.974 and 0.969, respectively). Using a cut-off value of 25.5, the VI yielded a sensitivity of 82.3% and a specificity of 99.3% for cervical lesion detection. Conclusions: The SMI parameter (VI) exhibited a significantly higher value in cervical cancer compared to high-grade CIN, with a high level of agreement among observers. These findings suggest that quantitative SMI holds promise as an imaging technique for the detection and characterization of cervical lesions.

13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(4): 770-777, 2023 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-37666768

RESUMEN

This research aims to investigate the encapsulation and controlled release effect of the newly developed self-assembling peptide R-LIFE-1 on exosomes. The gelling ability and morphological structure of the chiral self-assembling peptide (CSAP) hydrogel were examined using advanced imaging techniques, including atomic force microscopy, transmission electron microscopy, and cryo-scanning electron microscopy. The biocompatibility of the CSAP hydrogel was assessed through optical microscopy and fluorescent staining. Exosomes were isolated via ultrafiltration, and their quality was evaluated using Western blot analysis, nanoparticle tracking analysis, and transmission electron microscopy. The controlled release effect of the CSAP hydrogel on exosomes was quantitatively analyzed using laser confocal microscopy and a BCA assay kit. The results revealed that the self-assembling peptide R-LIFE-1 exhibited spontaneous assembly in the presence of various ions, leading to the formation of nanofibers. These nanofibers were cross-linked, giving rise to a robust nanofiber network structure, which further underwent cross-linking to generate a laminated membrane structure. The nanofibers possessed a large surface area, allowing them to encapsulate a substantial number of water molecules, thereby forming a hydrogel material with high water content. This hydrogel served as a stable spatial scaffold and loading matrix for the three-dimensional culture of cells, as well as the encapsulation and controlled release of exosomes. Importantly, R-LIFE-1 demonstrated excellent biocompatibility, preserving the growth of cells and the biological activity of exosomes. It rapidly formed a three-dimensional network scaffold, enabling the stable loading of cells and exosomes, while exhibiting favorable biocompatibility and reduced cytotoxicity. In conclusion, the findings of this study support the notion that R-LIFE-1 holds significant promise as an ideal tissue engineering material for tissue repair applications.


Asunto(s)
Exosomas , Preparaciones de Acción Retardada , Hidrogeles , Microscopía Electrónica de Rastreo , Péptidos
14.
ACS Appl Mater Interfaces ; 15(29): 34360-34377, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37432741

RESUMEN

Having no specific therapy for triple-negative breast cancer (TNBC), this subtype has the lowest survival rate and highest metastatic risk of breast cancer since the tumor inflammatory microenvironment mainly accounts for heterogeneity-induced insensitivity to chemotherapy and epithelial-mesenchymal transition (EMT). This study reports hyaluronic acid (HA)-modified liposomes loaded with cisplatin (CDDP) and hesperetin (Hes) (CDDP-HA-Lip/Hes) for active targeting to relieve systematic toxicity and effective anti-tumor/anti-metastasis ability of TNBC. Our results revealed that HA modification promoted the cellular uptake of the synthesized CDDP-HA-Lip/Hes nanoparticles in MDA-MB-231 cells and accumulation in tumor sites in vivo, indicating deeper tumor penetration. Importantly, CDDP-HA-Lip/Hes inhibited the PI3K/Akt/mTOR pathway to alleviate the inflammation in the tumor and with a crosstalk to suppress the process of the EMT, increasing the chemosensitivity and inhibiting tumor metastasis. Meanwhile, CDDP-HA-Lip/Hes could significantly inhibit the aggression and metastasis of TNBC with less side effects on normal tissues. Overall, this study provides a tumor-targeting drug delivery system with great potential for treating TNBC and its lung metastasis robustly.


Asunto(s)
Cisplatino , Neoplasias de la Mama Triple Negativas , Humanos , Cisplatino/uso terapéutico , Liposomas , Neoplasias de la Mama Triple Negativas/metabolismo , Ácido Hialurónico/uso terapéutico , Fosfatidilinositol 3-Quinasas , Línea Celular Tumoral , Agresión , Microambiente Tumoral
15.
Cancers (Basel) ; 15(12)2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37370696

RESUMEN

BACKGROUND: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2-1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. STUDY DESIGN: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, and Web of Science by two teams of investigators. Analysis was run using R packages. RESULTS: A total of 12 publications including seven randomized control, two prospective, and three retrospective trials with a total of 1346 patients were included for analysis. The average follow-up for all patients was 41 ± 23.8 months. Demographics, pre-treatment calcium, PTH, and bone mineral density (BMD) were similar between the medical (N = 632) and surgical (N = 714) cohorts. Post-treatment calcium and PTH levels were significantly higher in the medical cohort (10.46 vs. 9.39, p < 0.01), (106.14 vs. 43.25, p = 0.001), respectively. Interestingly, the post-treatment PTH in the medical cohort increased when compared to pre-treatment (83.84 to 106.14). Patients in the medical cohort had lower BMD in lumbar (0.48 g/cm2; OR = 0.42, 95% CI = 0.21, 0.83), femoral (0.48; OR = 0.42, 95% CI = 0.29, 0.61), and hip (0.61; OR = 0.33, 95% CI = 0.13, 0.85). Incidences of fracture, nephrolithiasis, cardiovascular death, or overall mortality were not significantly different between the cohorts. CONCLUSIONS: The present study is the most comprehensive meta-analysis on mild pHPT to date. Our findings reflect that parathyroidectomy is the superior option in the treatment of mild pHPT patients as opposed to medical management.

16.
Breast Cancer Res ; 25(1): 3, 2023 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-36635685

RESUMEN

The chemotherapy of triple-negative breast cancer based on doxorubicin (DOX) regimens suffers from great challenges on toxicity and autophagy raised off-target. In this study, a conjugate methotrexate-polyethylene glycol (shorten as MTX-PEG)-modified CG/DMMA polymeric micelles were prepared to endue DOX tumor selectivity and synergistic autophagic flux interference to reduce systematic toxicity and to improve anti-tumor capacity. The micelles could effectively promote the accumulation of autophagosomes in tumor cells and interfere with the degradation process of autophagic flux, collectively inducing autophagic death of tumor cells. In vivo and in vitro experiments showed that the micelles could exert improved anti-tumor effect and specificity, as well as reduced accumulation and damage of chemotherapeutic drugs in normal organs. The potential mechanism of synergistic autophagic death exerted by the synthesized micelles in MDA-MB-231 cells has been performed by autophagic flux-related pathway.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Micelas , Metotrexato , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Doxorrubicina , Polímeros
17.
J Control Release ; 353: 327-336, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36464063

RESUMEN

Tumor-derived exosomes (TDEs) are the particular communicator and messenger between tumor cells and other cells containing cancer-associated genetic materials and proteins. And TDEs who are also one of the important components consisting of the tumor microenvironment (TME) can reshape and interact with TME to promote tumor development and metastasis. Moreover, due to their long-distance transmission by body fluids, TDEs can facilitate the formation of pre-metastatic niche to support tumor colonization. We discuss the main characteristics and mechanism of TDE-mediated tumor metastasis by reshaping TME and pre-metastatic niche as well as the potential of TDEs for diagnosing tumor and predicting future metastatic development.


Asunto(s)
Exosomas , Neoplasias , Humanos , Exosomas/metabolismo , Microambiente Tumoral , Neoplasias/metabolismo , Metástasis de la Neoplasia
18.
Anal Chem ; 95(2): 966-975, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36584292

RESUMEN

Clustered regularly interspaced short palindromic repeats (CRISPR)-based assays have been an emerging diagnostic technology for pathogen diagnosis. In this work, we developed a polydisperse droplet digital CRISPR-Cas-based assay (PddCas) for the rapid and ultrasensitive amplification-free detection of viral DNA/RNA with minimum instruments. LbaCas12a and LbuCas13a were used for the direct detection of viral DNA and RNA, respectively. The reaction mixtures were partitioned with a common vortex mixer to generate picoliter-scale polydisperse droplets in several seconds. The limit of detection (LoD) for the target DNA and RNA is approximately 100 aM and 10 aM, respectively, which is about 3 × 104-105 fold more sensitive than corresponding bulk CRISPR assays. We applied the PddCas to successfully detect severe acute respiratory syndrome coronavirus (SARS-CoV-2) and human papillomavirus type 18 (HPV 18) in clinical samples. For the 23 HPV 18-suspected cervical epithelial cell samples and 32 nasopharyngeal swabs for SARS-CoV-2, 100% sensitivity and 100% specificity were demonstrated. The dual-gene virus detection with PddCas was also established and verified. Therefore, PddCas has potential for point-of-care application and is envisioned to be readily deployed for frequent testing as part of an integrated public health surveillance program.


Asunto(s)
COVID-19 , Infecciones por Papillomavirus , Humanos , ADN Viral/genética , ARN Viral/genética , Sistemas CRISPR-Cas/genética , SARS-CoV-2/genética , Papillomavirus Humano 18
19.
Gels ; 8(12)2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36547294

RESUMEN

Patient-derived organoid (PDO) models have been widely used in precision medicine. The inability to standardize organoid creation in pre-clinical models has become apparent. The common mouse-derived extracellular matrix can no longer meet the requirements for the establishment of PDO models. Therefore, in order to develop effective methods for 3D cultures of organoids, we designed a self-assembling peptide, namely DRF3, which can be self-assembled into ordered fibrous scaffold structures. Here, we used the co-assembly of self-assembling peptide (SAP) and collagen type I, fibronectin, and laminin (SAP-Matrix) to co-simulate the extracellular matrix, which significantly reduced the culture time of PDO, improved the culture efficiency, and increased the self-assembly ability of cells. Compared with the results from the 2D cell line, the PDO showed a more significant expression of cancer-related genes. During organoid self-assembly, the expression of cancer-related genes is increased. These findings provide a theoretical basis for the establishment of precision molecular modeling platforms in the future.

20.
Neurosurg Focus ; 53(4): E7, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36183180

RESUMEN

OBJECTIVE: In this systematic review the authors aimed to evaluate the effectiveness and superiority of radiomics in detecting tiny epilepsy lesions and to conduct original research in the use of radiomics for preliminary prediction of postoperative seizures in patients with dysembryoplastic neuroepithelial tumor (DNET). METHODS: The PubMed and Web of Science databases were searched from the earliest record, January 1, 2018, to December 29, 2021, for reports of the detection of epilepsy using radiomics, and the resulting articles were carefully checked according to the PRISMA 2020 guidelines. The authors then conducted original research by evaluating MR images in 18 patients, who were then separated into two groups, the epilepsy recurrence group (ERG) and the epilepsy nonrecurrence group. The tumor region and the edema region were segmented manually by 3D Slicer. The radiomics data were extracted from MR images by using "Slicer Radiomics" running on Mac OS X. Tumor regions were observed with T1-weighted imaging, and edema with FLAIR imaging. Radiomics features with significant differences were selected through comparison according to epilepsy relapses performed with the Mann-Whitney U-test. The edema and tumor regions were also compared within groups to identify their distinctive features. Radiomics features were tested to verify their ability to predict recurrence epilepsy by receiver operating characteristic curve. RESULTS: This systematic review located 9 original articles related to epilepsy and radiomics published from 2018 to 2021. The reported studies demonstrated that radiomics is useful for detecting tiny epilepsy lesions. Among the radiomics features used, the predictive ability of the area under the curve was more than 0.8. The heterogeneity of the peritumoral edema region was found to be higher in the ERG. CONCLUSIONS: Satellite lesions in the peritumoral edema region of DNET patients may cause epilepsy recurrence, and radiomics is an emerging method to detect and evaluate these epilepsy-associated lesions.


Asunto(s)
Neoplasias Encefálicas , Epilepsia , Glioma , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Niño , Glioma/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Convulsiones/diagnóstico por imagen , Convulsiones/etiología , Convulsiones/cirugía
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