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1.
J Control Release ; 372: 482-493, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38914205

RESUMEN

The development of high-purity antigens promotes the urgent need of novel adjuvant with the capability to trigger high levels of immune response. Polyinosinic-polycytidylic (Poly(I:C)) is a synthetic double-stranded RNA (dsRNA) that can engage Toll-like receptor 3 (TLR3) to initiate immune responses. However, the Poly(I:C)-induced toxicity and inefficient delivery prevent its applications. In our study, combination adjuvants are formulated by aluminum oxyhydroxide nanorods (AlOOH NRs) and Poly(I:C), named Al-Poly(I:C), and the covalent interaction between the two components is further demonstrated. Al-Poly(I:C) mediates enhanced humoral and cellular immune responses in three antigen models, i.e., HBsAg virus-like particles (VLPs), human papilloma virus (HPV) VLPs and varicella-zoster virus (VZV) glycoprotein E (gE). Further mechanistic studies demonstrate that the dose and molecular weight (MW) of Poly(I:C) determine the physicochemical properties and adjuvanticity of the Al-Poly(I:C) combination adjuvants. Al-Poly(I:C) with higher Poly(I:C) dose promotes antigen-bearing dendritic cells (DCs) recruitment and B cells proliferation in lymph nodes. Al-Poly(I:C) formulated with higher MW Poly(I:C) induces higher activation of helper T cells, B cells, and CTLs. This study demonstrates that Al-Poly(I:C) potentiates the humoral and cellular responses in vaccine formulations. It offers insights for adjuvant design to meet the formulation requirements in both prophylactic and therapeutic vaccines.

2.
World J Clin Cases ; 12(15): 2551-2559, 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38817222

RESUMEN

BACKGROUND: Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus. It is the most common gynecological disorder, affecting up to 80% of women of reproductive age. Uterine fibroids can cause various symptoms such as abnormal uterine bleeding, pelvic pain, infertility, and pregnancy complications. The treatment options for uterine fibroids include medical therapy, surgical intervention, and minimally invasive techniques. AIM: To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization (UAE). METHODS: This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE, and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments. The two groups were matched for age, body mass index, parity, and baseline characteristics of uterine fibroids. The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), as well as ovarian reserve tests, such as antral follicle count (AFC) and ovarian volume (OV). The secondary outcome was fertility that was evaluated based on the menstrual cycle, ovulation, conception, pregnancy, and delivery. The participants were followed-up for 36 months and assessed at 1, 3, 6, 12, 24, and 36 months after treatment. RESULTS: The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women, resolving within a week. No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones (FSH, LH, E2, AMH) and ovarian reserve indicators (AFC, OV) at any point up to 36 months post-treatment. Additionally, there were no significant differences in conception, pregnancy, or delivery rates, with the average time to conception and gestational age at delivery being similar between the two groups. Birth weights were also comparable. Finally, there was no significant correlation between ovarian function, fertility indicators, and the type or amount of embolic agent used or the change in fibroids post-treatment. CONCLUSION: UAE resulted in significantly positive pregnancy outcomes, no adverse events post-treatment, and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

3.
Front Neurol ; 15: 1374093, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38685948

RESUMEN

Background: Mechanical thrombectomy (MT) is one of the effective treatment methods for acute ischemic stroke (AIS), which requires a period of dual antiplatelet therapy (DAPT) after endovascular treatment. This study aimed to compare the efficacy and safety of 3-month DAPT and 1-month DAPT in AIS patients receiving MT through a retrospective study. Methods: AIS patients who received MT from May 2018 to March 2023 were grouped into a 1-month group (1-M group) and a 3-month group (3-M group) according to the duration of DAPT after MT. The primary outcome was the mRS score at 90 days. Secondary outcomes included a good prognosis (mRS score of 0-2) at 90 days post-surgery, 6-month mortality, recurrence of cerebral infarction, Barthel's index, Montreal Cognitive Assessment (MoCA) score, and incidence of symptomatic intracranial hemorrhage (sICH) during hospitalization. Result: A total of 147 patients with AIS were included in the final analysis, with 78 patients in the 1-M group and 69 patients in the 3-M group. The baseline and neurological characteristics were comparable between both groups. At 3-month follow-up, a total of 61 patients had an mRS of 0-2 at 90 days, with an average mRS of 3.3 ± 0.9 for all patients. There was no statistically significant difference in the mRS between the two groups of patients at 90 days (P > 0.05). There was no statistically significant difference in the mortality rate and incidence of sICH between the two groups of patients during the 6-month follow-up period (P > 0.05), but the recurrence rate of AIS in the 3-M group was lower than that in the 1-M group (P < 0.05). The improvement of Barthel index and MoCA in patients in the 3-M group was higher than those in the 1-M group at 6 months but not statistically different (P > 0.05). Conclusion: For AIS patients undergoing mechanical thrombectomy, compared to 1-month DAPT, 3-month DAPT can reduce the recurrence rate of IS during a 6-month follow-up period, without increasing the mortality and risk of cerebral hemorrhage.

4.
Biomaterials ; 308: 122569, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38626556

RESUMEN

In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5' or 3' end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3'-end exposure, the 5'-end exposure of CpG in combination adjuvants (Al-CpG-5') enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5' enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5' allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting Tfh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines.


Asunto(s)
Adyuvantes Inmunológicos , Hidróxido de Aluminio , Óxido de Aluminio , Células Dendríticas , Antígenos de Superficie de la Hepatitis B , Nanopartículas , Oligodesoxirribonucleótidos , Adyuvantes Inmunológicos/farmacología , Animales , Nanopartículas/química , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/farmacología , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/metabolismo , Hidróxido de Aluminio/química , Hidróxido de Aluminio/farmacología , Ratones , Ratones Endogámicos C57BL , Femenino , Citocinas/metabolismo , Compuestos de Alumbre/química , Compuestos de Alumbre/farmacología
5.
Hepatol Int ; 18(2): 582-594, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37823937

RESUMEN

BACKGROUND AND AIMS: T cells are master effectors of anti-tumor immunity in cancer. Recent studies suggest that altered lipid metabolism imposed by the tumor microenvironment constrains anti-tumor immunity. However, the tumor-associated lipid species changes that dampen T cell ability to control tumor progression are not fully understood. Here, we plan to clarify the influences of distinctly altered lipid components in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) on T-cell function, aiming to seek lipid metabolic targets for improving T cell anti-tumor effects. METHODS: Tumor tissues and non-tumor liver from HCC patients were collected for RNA-sequencing, lipid profiling and T cell characterizing, followed by correlation analysis. Additionally, the effects of significantly changed lipid components on anti-tumor potential of T cells were tested by in vitro cell experiments and/or in vivo tumor inoculated model. RESULTS: Altered lipid metabolism coincides with impaired T cell response in HBV-related HCC. Characteristic lipid composition, significantly marked by accumulation of long-chain acylcarnitines (LCACs) and reduction of lysophosphatidylcholines (LPCs), are found in the tumor tissue. Notably, LCACs accumulated are associated with T cells exhaustion and deficient functionality, while LPCs correlate to anti-tumor effects of T cells. In particular, supplement of LPCs, including LPC (20:0) and LPC (22:0), directly promote the activation and IFN-γ secretion of T cells in vitro, and suppress tumor growth in vivo. CONCLUSIONS: Our study highlights the distinctly changed lipid components closely related to T cell dysregulation in HCC, and suggests a promising strategy by decreasing LCACs and increasing LPCs for anti-tumor immunotherapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Linfocitos T , Inmunoterapia , Lípidos , Microambiente Tumoral
6.
Org Lett ; 26(1): 298-303, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38153355

RESUMEN

A rational combination of photoredox catalyst anthraquinone and hydrogen atom transfer (HAT) catalyst methyl thioglycolate allows for the rapid and straightforward conversion of a range of 2-amidated acetylenic alcohols to multifunctional N,O-spirocycles under visible light irradiation. With oxygen as the sole terminal oxidant, these reactions can be carried out efficiently at room temperature without the involvement of transition metals or strong oxidants. The successful application of this mild catalytic strategy in the late-stage functionalization of bioactive skeletons further highlights its practical value.

7.
Curr Opin Biotechnol ; 84: 103013, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37897860

RESUMEN

Polydopamine (PDA) nanoparticles (NPs) have diverse nanomedicine applications owing to their biocompatibility and abundant entry to cells. Yet, our knowledge in their interactions with cells was infrequently studied until recent years. This review presents the latest insights into the cell-nano interactions of PDA NPs, including their 'self-targeting' to dopamine receptors for cellular entry without the aid of ligands, in vitro 'self-therapeutic' cellular responses (antiferroptosis, macrophage polarization, and modulation of mitochondrial bioenergetics) in the absence of drugs, and in vivo cellular localization and pharmacological properties upon various routes of administration. This review concludes with our perspectives on the therapeutic promise of PDA NPs and the need for studies on PDA biochemistry, biodegradability, and protein adsorption.


Asunto(s)
Nanopartículas , Polímeros , Polímeros/química , Nanopartículas/química , Indoles/química , Indoles/farmacología
8.
Clin Spine Surg ; 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37735759

RESUMEN

We report the case of a 3-year-old child with Loeys-Dietz syndrome, a rare genetic connective tissue disorder. The young girl had concurrent cervical kyphosis, atlantoaxial dislocation (AAD), and spinal cord compression. Posterior occipitocervical fusion was performed. Postoperative examination and clinical manifestations confirmed that all pedicle screws were satisfactorily placed, cervical kyphosis and AAD were corrected, and spinal cord compression was relieved. At the 1-year postoperative follow-up, the patient had recovered well, indicating that our operation was successful. To the best of our knowledge, this is the first reported surgical case of cervical kyphosis and AAD caused by Loeys-Dietz syndrome.

9.
Front Surg ; 10: 1059544, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37025272

RESUMEN

Background: Structural autografts harvested from the iliac bone have been used in atlantoaxial fusion; they have been the gold standard for years. However, emerging occipital bone grafts have the advantage of avoiding donor-site morbidity and complications. Thus, we compared the clinical outcomes of structural autografts from the occipital bone or iliac crest and discussed the clinical significance of occipital bone grafts in pediatric patients. Methods: Pediatric patients who underwent posterior fusion using occipital bone grafts (OBG) or iliac bone grafts (IBG) between 2017 and 2021 were included in this study. Data on clinical outcomes, including operation time, estimated blood loss, length of hospitalization, complications, fusion rate, and fusion time, were collected and analyzed. Additionally, 300 pediatric patients who underwent cranial computed tomography scans were included in the bone thickness evaluation procedure. The central and edge thicknesses of the harvested areas were recorded and analyzed. Results: Thirty-nine patients were included in this study. There were no significant differences in patient characteristics between the OBG and IBG groups. Patients in both groups achieved a 100% fusion rate; however, the fusion time in the OBG group was significantly longer than that in the IBG group. Estimated blood loss, operation time, and length of hospitalization were significantly lower in the OBG group than those in the IBG group. The surgery-related complication rate was lower, but not significantly, in the OBG group than that in the IBG group. For occipital bone thickness evaluation, a significant difference in the central part of the harvesting area was found between the young and old groups, with no significant sex differences. Conclusion: The use of OBG for atlantoaxial fusion is acceptable for pediatric patients with atlantoaxial dislocation, avoiding donor-site morbidity and complications.

10.
Front Nutr ; 10: 1073894, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37081919

RESUMEN

Background: Vitamin D deficiency is common in critically ill patients with suspected infection and is strongly associated with the predisposition of sepsis and a poor prognosis. The effectiveness of vitamin D supplementation for preventing sepsis remains unclear. This retrospective cohort study investigated the effect of vitamin D supplementation on sepsis prophylaxis in critically ill patients with suspected infection. Methods: This retrospective cohort study included 19,816 adult patients with suspected infection in intensive care units (ICU) from 2008 to 2019 at the Beth Israel Deaconess Medical Center, Boston, USA. The included patients were divided into the vitamin D cohort or non-vitamin D cohort according to vitamin D administration status. The primary outcomes were the incidence of sepsis in ICU. The secondary outcomes included 28-day all-cause mortality, length of ICU and hospital stay and the requirements of vasopressors or mechanical ventilation. A propensity score matching cohort was used to test the differences in primary and secondary outcomes between groups. Results: The results showed that vitamin D supplementation demonstrated a lower risk of sepsis (odd ratio 0.46; 95% CI 0.35-0.60; P < 0.001) and a lower risk of new mechanical ventilation requirement (odd ratio 0.70; 95% CI 0.53-0.92; P = 0.01), but no significant difference in the risk of 28-day mortality was observed (hazard ratio 1.02; 95% CI 0.77-1.35; P = 0.89). In the sensitive analysis, among the patients who suspected infection within 24 h before or after ICU admission, a lower risk of sepsis and a lower percentage of new mechanical ventilation also were detected in the vitamin D cohort. Conclusion: Vitamin D supplementation may have a positively prophylactic effect on sepsis in critically ill patients with suspected infection.

11.
World Neurosurg ; 175: e574-e581, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37028486

RESUMEN

OBJECTIVE: To investigate the efficacy and safety of posterior atlantoaxial fusion (AAF) with C1-2 pedicle screw fixation for atlantoaxial dislocation (AAD) in pediatric patients with mucopolysaccharidosis IVA (MPS IVA). METHODS: This study included 21 pediatric patients with MPS IVA who underwent posterior AAF with C1-2 pedicle screw fixation. Anatomical parameters of the C1 and C2 pedicle were measured on preoperative computed tomography (CT). The American Spinal Injury Association (ASIA) scale was used to evaluate the neurological status. The fusion and accuracy of pedicle screw was assessed on postoperative CT. Demographic, radiation dose, bone density, surgical, and clinical data were recorded. RESULTS: Patients reviewed included 21 patients younger than 16 years with an average age of 7.4 ± 4.2 years and an average of 20.9 ± 7.7 months follow-up. Fixation of 83 C1 and C2 pedicle screws was performed successfully and 96.3% of them were identified as being safe. One patient developed postoperative transient disturbance of consciousness and one developed fetal airway obstruction and died about 1 month after the surgery. Out of the remaining20 patients, fusion was achieved, symptoms were improved, and no other serious surgical complications were observed at the latest follow-up. CONCLUSIONS: Posterior AAF with C1-2 pedicle screw fixation is effective and safe for AAD in pediatric patients with MPS IVA. However, the procedure is technically demanding and should be performed by experienced surgeons with strict multidisciplinary consultations.


Asunto(s)
Articulación Atlantoaxoidea , Luxaciones Articulares , Inestabilidad de la Articulación , Mucopolisacaridosis , Mucopolisacaridosis IV , Traumatismos del Cuello , Tornillos Pediculares , Fusión Vertebral , Traumatismos Vertebrales , Espondiloartropatías , Humanos , Niño , Preescolar , Mucopolisacaridosis IV/cirugía , Fusión Vertebral/métodos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/cirugía , Articulación Atlantoaxoidea/diagnóstico por imagen , Articulación Atlantoaxoidea/cirugía , Inestabilidad de la Articulación/cirugía , Vértebras Cervicales/cirugía
12.
Int Angiol ; 42(3): 260-267, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36744426

RESUMEN

BACKGROUND: The arteriovenous malformation (AVM) represents a complicated pathology with high recurrence risk. This study aimed at reporting the clinical outcome of embolotherapy in treating extremity AVMs and exploring the potential risk factors for the recurrence of the lesion. METHODS: A multicenter retrospective review of the electronic medical records database was performed to enroll extremity AVM cases. Based on the follow-up findings, patients were allocated into the recurrence group and non-recurrence group. Univariable comparisons were performed to find relevant factors for AVM recurrence, then each potential factor was assessed by Kaplan-Meier analysis to determine whether it could influence the time-dependent recurrence possibility. RESULTS: Between January 2010 and December 2020, we screened 339 cases and enrolled 35 patients (24 male, average age: 45.23±17.57 years). During an average follow-up period of 5.91±3.22 months, recurrence of AVM was found in 18 cases. Univariable analysis documented type IIIb AVM and previous surgical attempts potentially indicated a high recurrence possibility, whereas type II, application of coil and ethanol during the intervention, as well as optimal embolization might be helpful to control the pathology. Of these relevant factors, further Kaplan-Meier analysis found that previous surgical attempts (P=0.002), application of ethanol (P=0.015), AVM type II (P=0.048), and IIIb (P=0.030) might have a significant impact on recurrence probability. CONCLUSIONS: Previous surgical attempts might increase the recurrence risk after embolotherapy of the AVM, whereas using ethanol as the embolic agent seems to contribute to a lower recurrence probability. Type II AVM may respond better to embolization than type IIIb.


Asunto(s)
Malformaciones Arteriovenosas Intracraneales , Humanos , Masculino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Estudios Retrospectivos , Estudios de Seguimiento , Malformaciones Arteriovenosas Intracraneales/cirugía , Extremidades , Etanol
13.
Cell Mol Gastroenterol Hepatol ; 15(5): 1181-1198, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36787843

RESUMEN

BACKGROUND & AIMS: CD161-expressing CD8+ T cells consist of mucosal-associated invariant T cells with semi-invariant T-cell receptor (TCR) use and non-mucosal-associated invariant T CD161+CD8+ T cells with polyclonal TCR repertoire. Although CD161+CD8+ T cells are enriched in liver and embrace hepatitis B virus (HBV)-specific T cells in chronic hepatitis B (CHB) patients, their roles in disease progression remain poorly understood. This study aimed to decipher their profiling and dynamic changes during chronic HBV infection. METHODS: Blood samples from 257 CHB patients and nontumor liver specimens from 73 HBV-positive patients were analyzed for CD161+CD8+ T-cell characterization by flow cytometry, TCR repertoire determination, transcriptomic analyses, and cell experiments. RESULTS: CD161+CD8+ T cells were increased and hyperactivated in patients, while positive correlation between the CD161+CD8+ T-cell ratio and HBV-DNA level suggested this was insufficient to control HBV replication. The overlap of complementarity determining region 3 sequences supported the switch between CD161-CD8+ and CD161+CD8+ populations. Although CD161+CD8+ T cells were endowed with innateness phenotype and enhanced antiviral capacity, the population from patients had impaired type I cytokine production, and increased interleukin 17 and granzyme B secretion. The increased CD161+CD8+ T cells and their increased granzyme B secretion correlated positively with inflammation-associated liver injury. Hepatic CD161+CD8+ T cells showed neutrophil-related pathogenic potential because they had increased transcript signatures and proinflammatory cytokine production in neutrophil recruitment- and response-related pathways that changed consistently in the injured liver. CONCLUSIONS: Our results highlight the reduced antiviral potency but increased pathogenic potential of CD161+CD8+ T cells in CHB patients, supporting CD161 expression as a marker of pathogenic CD8+ T subset and the intervention target for liver injury.


Asunto(s)
Linfocitos T CD8-positivos , Hepatitis B Crónica , Humanos , Antivirales , Granzimas , Virus de la Hepatitis B , Subfamilia B de Receptores Similares a Lectina de Células NK/inmunología
14.
Eur J Nutr ; 62(3): 1503-1516, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36692589

RESUMEN

PURPOSE: We aimed to describe the vitamin D status and its distribution in different age groups, sexes, seasons, and provinces of a large Chinese population. METHODS: This study retrospectively analyzed 1,528,685 results of serum 25-hydroxyvitamin D (25(OH)D) in the central laboratory of KingMed Diagnostics. The samples were from the individuals aged 0-119 years old in 30 provinces of China. Serum 25(OH)D was measured by an accurate commercial liquid chromatography-tandem mass spectrometry (LC-MS/MS) method from January 2017 to December 2019. The subjects were stratified by age, sex, the season of blood collection, and the province of residence. RESULTS: The median 25(OH)D concentration was 25.5 ng/mL (interquartile range (IQR) 18.7-32.7 ng/mL) in males and 20.8 ng/mL (IQR 14.4-28.2 ng/mL) in females. Overall, the median 25(OH)D concentration decreased with age in both males and females. Males had a 0.2-2.4 ng/mL higher median 25(OH)D concentration than females in different age groups. Vitamin D deficiency (25(OH)D < 15 ng/mL for the individuals under 14 years old; < 20 ng/mL for the individuals over 14 years old) was found in 21.3% of males and 43.6% of females. Significant seasonal variation of serum 25(OH)D concentrations was repeatedly observed in 3 years, with median concentration higher in summer (25.3 ng/mL (IQR 19.3-31.9 ng/mL)) and lower in winter (18.5 ng/mL (IQR 12.3-26.6 ng/mL)). Vitamin D status varied by province. The median 25(OH)D concentration was the highest in Hainan (31.0 ng/mL (IQR 24.9-39.2 ng/mL)) and the lowest in Qinghai (14.4 ng/mL (IQR 9.6-20.0 ng/mL)). 25(OH)D2 was detected in 12.2% of the results, and no significant seasonal variation was observed. CONCLUSION: In China, vitamin D deficiency is prevalent in the population participating in clinical vitamin D measurement. Age and sex differences in vitamin D levels were observed in our study. Seasonal variation and provincial differences are important aspects of serum vitamin D status. 25(OH)D2 cannot be ignored entirely in clinical measurement practice in China.


Asunto(s)
Espectrometría de Masas en Tándem , Deficiencia de Vitamina D , Humanos , Femenino , Masculino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estaciones del Año , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Estudios Retrospectivos , Pueblos del Este de Asia , Vitamina D , Calcifediol , Vitaminas , Deficiencia de Vitamina D/epidemiología , 25-Hidroxivitamina D 2
15.
Cancer Res ; 83(4): 582-594, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36512635

RESUMEN

CD1d-restricted invariant natural killer T (iNKT) cells actively patrol the liver and possess valuable antitumor potential. However, clinical trials evaluating administration of iNKT cell-specific agonist α-galactosylceramide (α-GalCer) have failed to achieve obvious tumor regression. Improving the efficacy of iNKT cell-based immunotherapy requires a better understanding of the factors restraining the clinical benefits. In the context of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we found circulating and hepatic iNKT cells were hyperactivated but demonstrated imbalances in ratio and defective α-GalCer responsiveness. Exogenous IL2 helped to expand residual α-GalCer-responsive clones with reduced T-cell receptor diversity. However, transcriptome-wide analysis revealed activation of the senescence-associated secretory phenotype and dampened cytotoxicity in iNKT cells, weakening their immune surveillance capacity. The senescent status of iNKT cells from the patients was further illustrated by cell-cycle arrest, impaired telomere maintenance, perturbed calcium transport-related biological processes, and altered metabolism. Lipidomic profiling revealed the accumulation of long-chain acylcarnitines (LCAC) and aberrant lipid metabolism in HCC tissue. Exogenous LCACs, especially palmitoyl-carnitine and stearoyl-carnitine, inhibited iNKT cell expansion and promoted senescence. Collectively, our results provide deeper insights into iNKT cell dysregulation and identify a cell senescence-associated challenge for iNKT cell-based immunotherapy in HBV-related HCC. The mechanistic links between iNKT cell senescence and accumulated LCACs suggest new targets for anti-HCC immunotherapies. SIGNIFICANCE: Patients with HBV-related HCC exhibit a cell senescence-associated dysregulation of invariant natural killer cells that is related to altered lipid metabolism and accumulated LCACs in tumor tissue.


Asunto(s)
Carcinoma Hepatocelular , Carnitina , Neoplasias Hepáticas , Células T Asesinas Naturales , Humanos , Antígenos CD1d , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carnitina/análogos & derivados , Carnitina/farmacología , Galactosilceramidas/farmacología , Neoplasias Hepáticas/metabolismo , Células T Asesinas Naturales/efectos de los fármacos , Células T Asesinas Naturales/metabolismo , Senescencia Celular/efectos de los fármacos
16.
Plants (Basel) ; 13(1)2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38202394

RESUMEN

The impact of ammonium (NH4+) stress on plant growth varies across species and cultivars, necessitating an in-depth exploration of the underlying response mechanisms. This study delves into elucidating the photosynthetic responses and differences in tolerance to NH4+ stress by investigating the effects on two wheat (Triticum aestivum L.) cultivars, Xumai25 (NH4+-less sensitive) and Yangmai20 (NH4+-sensitive). The cultivars were grown under hydroponic conditions with either sole ammonium nitrogen (NH4+, AN) or nitrate nitrogen (NO3-, NN) as the nitrogen source. NH4+ stress exerted a profound inhibitory effect on seedling growth and photosynthesis in wheat. However, these effects were less pronounced in Xumai25 than in Yangmai20. Dynamic photosynthetic analysis revealed that the suppression in photosynthesis was primarily attributed to stomatal limitation associated with a decrease in leaf water status and osmotic potential. Compared to Yangmai20, Xumai25 exhibited a significantly higher leaf K+ concentration and TaAKT1 upregulation, leading to a stronger stomatal opening and, consequently, a better photosynthetic performance under NH4+ stress. In conclusion, our study suggested stomatal limitation as the primary factor restricting photosynthesis under NH4+ stress. Furthermore, we demonstrated that improved regulation of osmotic substances contributed to higher stomatal conductance and enhanced photosynthetic performance in Xumai25.

17.
Cell Mol Biol (Noisy-le-grand) ; 68(7): 129-134, 2022 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-36495507

RESUMEN

The study aimed to explore the clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in treating cirrhotic portal hypertension and relevant influencing factors. 100 patients with cirrhotic portal hypertension receiving TIPS in the 980 hospitals of PLA logistic force from January 2015 to January 2018 were enrolled. Blood was collected from patients to detect liver function indicators [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], renal function indicators [blood urea nitrogen (BUN) and creatinine (Cr)], glucose metabolism indicators [insulin and glucose (GLU)] and inflammatory factors [interleukin-6 (IL-6), IL-8 and CXCL9] before surgery and at1 and 6 month(s) after surgery. Surgical efficacy was evaluated. The physique of patients was examined. The portal venous pressure, diameter and hemorheological indicators of patients were measured. Additionally, postoperative complications and nursing satisfaction were observed. At 1 and 6 month(s) after an operation, the levels of AST, ALT, BUN, Cr, insulin, GLU and inflammatory factors IL-6, IL-8 and CXCL9 and the portal venous pressure were overtly reduced (p<0.05), the postoperative dry weight was increased (p<0.05), the postoperative nursing satisfaction was 97%, the patients with higher satisfaction had fewer complications (p<0.05), the diameter of the portal vein was notably lowered (p<0.05), while the blood flow rate was remarkably raised (p<0.05). After the application of TIPS in the treatment of cirrhotic portal hypertension, the liver function, renal function, glucose metabolism and portal venous pressure and flow rate of patients return to normal, and postoperative complications are clearly reduced after postoperative nursing, proving the overall efficacy. Hence, TIPS is worthy of popularization and application.


Asunto(s)
Hipertensión Portal , Derivación Portosistémica Intrahepática Transyugular , Humanos , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Interleucina-6 , Interleucina-8 , Cirrosis Hepática/complicaciones , Hipertensión Portal/cirugía , Hipertensión Portal/complicaciones , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Insulina , Glucosa , Estudios Retrospectivos
18.
Artículo en Inglés | MEDLINE | ID: mdl-36355742

RESUMEN

Visual patterns are basic elements in images and represent the discernible regularity in the visual world. Thus, mining visual patterns is a fundamental task in computer vision. Most previous studies consider that only one visual pattern exists in a category, and then builds up a one-to-one mapping using category label. In reality, however, many categories include multiple patterns, which are many-to-one mappings. Without knowing the information of patterns, few existing pattern mining methods can discover and distinguish varied patterns in a category. To tackle this problem, we propose a novel framework, PaclMap, which learns medium-grained features to represent patterns. It includes an unsupervised pattern-level contrastive learning and a multipattern activation map. Their joint optimization encourages the network to mine both discriminative and frequent patterns in a category. Extensive experiments conducted on four benchmark datasets (Place-20, imagenet large scale visual recognition challenge (ILSVRC)-20, visual object classes (VOC), and Travel) demonstrate that PaclMap outperforms six state-of-the-art methods with average improvements of 2.9% on accuracy and 12.3% on frequency, respectively.

19.
Medicine (Baltimore) ; 101(46): e31595, 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36401467

RESUMEN

BACKGROUND: Increasing evidence supports the efficacy and safety of prostatic artery embolization (PAE) in the treatment of benign prostatic hyperplasia. However, PAE relies on ionizing radiation, which has not been studied systematically so far. Therefore, the potential associated risks remain largely unknown and are subject to intense debate. We performed a protocol for systematic review and meta-analysis to evaluate the clinical benefits of different radiation doses in patients with benign prostatic hyperplasia undergoing PAE. METHODS: A comprehensive search of several databases from 1966 to October 2022 was conducted. The databases include Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and PubMed. Risk of bias of the included studies was assessed by the "Risk of Bias Assessment Tool" of the Cochrane Handbook for randomized controlled trials. All data were analyzed using the Comprehensive Meta-Analysis software package (Biostat, Engelwood, NJ). RESULTS: The results will be submitted to a peer-reviewed journal once completed. CONCLUSION: This review will provide reliable evidence for extensive application of PAE for benign prostatic hyperplasia and determine the most rational radiation dose for these patients.


Asunto(s)
Embolización Terapéutica , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/terapia , Hiperplasia Prostática/etiología , Próstata , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Resultado del Tratamiento , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto , Arterias , Dosis de Radiación , Literatura de Revisión como Asunto
20.
Nanomaterials (Basel) ; 12(19)2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36234419

RESUMEN

Endohedral metallofullerenes (EMFs) are one type of intriguing metal/carbon hybrid molecule with the molecule configuration of sphere cavity-encapsulating metal ions/metal clusters due to their unique physicochemical properties and corresponding application in the fields of biological materials, single molecule magnet materials and energy conversion materials. Although the EMF family is growing, and versatile EMFs have been successfully synthesized and confirmed using crystal structures, some expected EMF members have not been observed using the conventional fullerene separation and purify strategy. These missing EMFs raise an interesting scientific issue as to whether this is due to the difficulty in separating them from the in situ formed carbon soot. Herein, we successfully captured a long-sought dysprosium-based EMF bearing a C2v(5)-C80 cage (Dy@C2v(5)-C80) in the form of Dy@C2v(5)-C80(CH2Ph)(Ph = -C6H5) from carbon soot containing versatile EMFs using simple benzyl radical functionalization and unambiguously confirmed the molecule structure using single crystal X-ray diffraction characterization. Meanwhile, the crystal structure of Dy@C2v(5)-C80(CH2Ph) showed that a single benzyl group was grafted onto the (5,6,6)-carbon, suggesting the open-shell electronic configuration of Dy@C2v(5)-C80. The theoretical calculations unveiled that the benzyl radical addition enables the modulation of the electronic configuration of Dy@C2v(5)-C80 and the corresponding stabilization of Dy@C2v(5)-C80 in conventional organic solvents. This facile stabilization strategy via benzyl radical addition exhibits the considerable capability to capture these missing EMFs, with the benefit of enriching the endohedral fullerene family.

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