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1.
Cell Mol Neurobiol ; 44(1): 46, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743119

RESUMEN

Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), a subunit of major histocompatibility complex class I (MHC-I) molecules, plays a crucial role in the development and progression in certain CNS diseases. On the one hand, intracellular B2M was abnormally upregulated in brain tumors and regulated tumor microenvironments and progression. On the other hand, soluble B2M was also elevated and involved in pathological stages in CNS diseases. Targeted B2M therapy has shown promising outcomes in specific CNS diseases. In this review, we provide a comprehensive summary and discussion of recent advances in understanding the pathological processes involving B2M in CNS diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, and primary central nervous system lymphoma).


Asunto(s)
Enfermedades del Sistema Nervioso Central , Microglobulina beta-2 , Humanos , Microglobulina beta-2/metabolismo , Enfermedades del Sistema Nervioso Central/metabolismo , Enfermedades del Sistema Nervioso Central/patología , Animales
2.
J Med Syst ; 48(1): 52, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38761230

RESUMEN

This study aimed to analyze the current landscape of ChatGPT application in the medical field, assessing the current collaboration patterns and research topic hotspots to understand the impact and trends. By conducting a search in the Web of Science, we collected literature related to the applications of ChatGPT in medicine, covering the period from January 1, 2000 up to January 16, 2024. Bibliometric analyses were performed using CiteSpace (V6.2., Drexel University, PA, USA) and Microsoft Excel (Microsoft Corp.,WA, USA) to map the collaboration among countries/regions, the distribution of institutions and authors, and clustering of keywords. A total of 574 eligible articles were included, with 97.74% published in 2023. These articles span various disciplines, particularly in Health Care Sciences Services, with extensive international collaboration involving 73 countries. In terms of countries/regions studied, USA, India, and China led in the number of publications. USA ot only published nearly half of the total number of papers but also exhibits a highest collaborative capability. Regarding the co-occurrence of institutions and scholars, the National University of Singapore and Harvard University held significant influence in the cooperation network, with the top three authors in terms of publications being Wiwanitkit V (10 articles), Seth I (9 articles), Klang E (7 articles), and Kleebayoon A (7 articles). Through keyword clustering, the study identified 9 research theme clusters, among which "digital health"was not only the largest in scale but also had the most citations. The study highlights ChatGPT's cross-disciplinary nature and collaborative research in medicine, showcasing its growth potential, particularly in digital health and clinical decision support. Future exploration should examine the socio-economic and cultural impacts of this trend, along with ChatGPT's specific technical uses in medical practice.


Asunto(s)
Bibliometría , Humanos
3.
Front Neurol ; 15: 1368988, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665996

RESUMEN

Objective: Acupuncture, acknowledged as a potent non-pharmacological therapy, is frequently employed to alleviate pain. Despite its widespread use, there has been a lack of overarching bibliometric analysis of clinical research on acupuncture analgesia. We aimed to summarize current patterns, hotspots, and development trends in this field through bibliometric analysis. Methods: This study evaluates academic publications retrieved from the Web of Science database (2010.01-2023.09) concerning acupuncture analgesia in clinical settings. All primary and secondary studies on humans were included. To track global developmental trends, we employed several software for analyzing annual publication volumes, countries/regions, institutions, authors, cited authors, journals, cited journals, references, and keywords and to draw collaborative networks and reference co-citation network maps. Results: The final search encompassed 7,190 relevant studies, including 1,263 randomized controlled trials (RCTs) and 1,293 systematic reviews and meta-analyses. The results indicated a gradual increase in the number of annual publications on acupuncture analgesia in clinical practice. Among countries and institutions, China (2,139) and Chengdu University of Traditional Chinese Medicine (258) ranked first. Liang FR (89 articles) was the most prolific author, while MacPherson H (604) was the most cited author. MEDICINE (455) was the most productive journal, and Pain (2,473/0.20) ranked first in both the frequency and centrality of cited journals. Notably, the most frequently cited reference was a systematic review of individual patient data on acupuncture carried out for chronic pain that was published by Vickers Andrew J in 2012 (156). Burst analysis identified frontier research areas for 2010-2020, encompassing network meta-analysis, case reports, dry needling, lumbar disc herniation, cancer, post-herpetic neuralgia, insomnia, and bibliometric analysis. Conclusion: This study outlines current trends and potential future research hotspots in clinical acupuncture analgesia over the past decade. Findings emphasize the necessity for enhanced international collaboration to improve research output and translation.

4.
Chem Sci ; 15(10): 3524-3529, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38454999

RESUMEN

An unprecedented fluoroarylation of 1,1-difluoroallenes with a cost-effective nucleophilic fluoride reagent and aryldiazonium salts is reported. This visible light promoted gold-catalyzed reaction allows a stereo- and regioselective incorporation of both the fluorine atom and aryl group, enabling a straightforward construction of multi-substituted trifluoromethyl alkenes. Under the mild reaction conditions, a nice tolerance of diverse functional groups is achieved. The high regioselectivity for fluorine-incorporation is rationalized by considering the thermodynamic driving force of trifluoromethyl group formation, whereas the counterintuitive stereoselectivity that aryl is installed on the side of the bulkier γ-substituent is interpreted by alleviating the increasing 1,3-allylic interaction in the gold-coordinated allene intermediate en route to the product.

5.
Opt Express ; 32(3): 3221-3233, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297548

RESUMEN

We present the growth, spectroscopy, continuous-wave (CW) and passively mode-locked (ML) operation of a novel "mixed" tetragonal calcium rare-earth aluminate crystal, Yb3+:Ca(Gd,Y)AlO4. The absorption, stimulated-emission, and gain cross-sections are derived for π and σ polarizations. The laser performance of a c-cut Yb:Ca(Gd,Y)AlO4 crystal is studied using a spatially single-mode, 976-nm fiber-coupled laser diode as a pump source. A maximum output power of 347 mW is obtained in the CW regime with a slope efficiency of 48.9%. The emission wavelength is continuously tunable across 90 nm (1010 - 1100 nm) using a quartz-based Lyot filter. With a commercial SEmiconductor Saturable Absorber Mirror to initiate and maintain ML operation, soliton pulses as short as 35 fs are generated at 1059.8 nm with an average output power of 51 mW at ∼65.95 MHz. The average output power can be scaled to 105 mW for slightly longer pulses of 42 fs at 1063.5 nm.

6.
Opt Express ; 32(3): 3974-3979, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297606

RESUMEN

We report on the continuous-wave (CW) and, for what we believe to be the first time, passively mode-locked (ML) laser operation of an Yb3+-doped YSr3(PO4)3 crystal. Utilizing a 976-nm spatially single-mode, fiber-coupled laser diode as pump source, the Yb:YSr3(PO4)3 laser delivers a maximum CW output power of 333 mW at 1045.8 nm with an optical efficiency of 55.7% and a slope efficiency of 60.9%. Employing a quartz-based Lyot filter, an impressive wavelength tuning range of 97 nm at the zero level was achieved in the CW regime, spanning from 1007 nm to 1104 nm. In the ML regime, incorporating a commercially available semiconductor saturable absorber mirror (SESAM) to initiate and maintain soliton-like pulse shaping, the Yb:YSr3(PO4)3 laser generated pulses as short as 61 fs at 1062.7 nm, with an average output power of 38 mW at a repetition rate of ∼66.7 MHz.

7.
BMC Cancer ; 24(1): 123, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267913

RESUMEN

BACKGROUND: Brain metastasis is a common outcome in non-small cell lung cancer, and despite aggressive treatment, its clinical outcome is still frustrating. In recent years, immunotherapy has been developing rapidly, however, its therapeutic outcomes for primary lung cancer and brain metastases are not the same, suggesting that there may be differences in the immune microenvironment of primary lung cancer and brain metastases, however, we currently know little about these differences. METHODS: Seventeen paired samples of NSCLC and their brain metastases and 45 other unpaired brain metastases samples were collected for the current study. Immunohistochemical staining was performed on all samples for the following markers: immune checkpoints CTLA-4, PD-1, PD-L1, B7-H3, B7-H4, IDO1, and EphA2; tumor-infiltrating lymphocytes (TILs) CD3, CD4, CD8, and CD20; tumor-associated microglia/macrophages (TAMs) CD68 and CD163; and tumor proliferation index Ki-67. The differences in expression of these markers were compared in 17 paired samples, and the effect of the expression level of these markers on the prognosis of patients was analyzed in lung adenocarcinoma brain metastases samples. Subsequently, multiplex immunofluorescence staining was performed in a typical lung-brain paired sample based on the aforementioned results. The multiplex immunofluorescence staining results revealed the difference in tumor immune microenvironment between primary NSCLC and brain metastases. RESULTS: In 17 paired lesions, the infiltration of CTLA-4+ (P = 0.461), PD-1+ (P = 0.106), CD3+ (P = 0.045), CD4+ (P = 0.037), CD8+ (P = 0.008), and CD20+ (P = 0.029) TILs in brain metastases were significantly decreased compared with primary tumors. No statistically significant difference was observed in the CD68 (P = 0.954) and CD163 (P = 0.654) TAM infiltration between primary NSCLC and paired brain metastases. In all the brain metastases lesions, the expression of PD-L1 is related to the time interval of brain metastases in NSCLC. In addition, the Cox proportional hazards regression models showed high expression of B7-H4 (hazard ratio [HR] = 3.276, 95% confidence interval [CI] 1.335-8.041, P = 0.010) and CD68 TAM infiltration (HR = 3.775, 95% CI 1.419-10.044, P = 0.008) were independent prognosis factors for lung adenocarcinoma brain metastases patients. CONCLUSIONS: Both temporal and spatial heterogeneity is present between the primary tumor and brain metastases of NCSLC. Brain metastases lesions exhibit a more immunosuppressive tumor immune microenvironment. B7-H4 and CD68+ TAMs may have potential therapeutic value for lung adenocarcinoma brain metastases patients.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1 , Antígeno CTLA-4 , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral
8.
J Obstet Gynaecol ; 43(2): 2287125, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38069630

RESUMEN

BACKGROUND: This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in the prenatal screening of foetal aneuploidy-associated diseases at different gestational ages. METHODS: Briefly, cell-free foetal DNAs were extracted from plasma first, followed by DNA sequencing and bioinformatics analyses for chromosome aneuploidy (T21, T18, and T13), sex chromosome aneuploidy (SCA), and microdeletion/microduplication. Subsequently, the positive results were subject to karyotype analyses. RESULTS: The pregnant women included in this study were divided into six groups, and the results, such as chromosome diagnoses, and clinical phenotypes, were collected for data analyses. According to the results of the data analysis, the positivity rates of foetal chromosomal abnormalities in pregnant women under 20, 20-24, 25-29, 30-34, 35-39, and >40 years old were 0%, 0.17%, 0.25%, 0.27%, 0.60%, and 1.66%, respectively. The positive predictive value (PPV) in the 20-24 years group was 41.67%, that in the 25-29 years group was 62.5%, that in the 30-34 years group was 66.67%, that in the 35-39 years group was 90.74%, and that in the >40 years group was 90.32%. CONCLUSION: Overall, NIPT detection in elderly pregnant women has excellent clinical application value in reducing the incidence of either birth defects or abortion caused by invasive chromosome examination.


It is critical to diagnose foetal chromosome aneuploidy in time through prenatal screening to prevent birth defects. This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in prenatal screening of foetal aneuploidy-associated diseases at different gestational ages. A retrospective analysis based on NIPT screening data at a medical laboratory was performed. The results showed that the total positivity rate and total positive predictive value of trisomy 21, trisomy 18, and trisomy 13 in older pregnant women (≥35 years old) were significantly higher than those in younger pregnant women, and there was an increasing trend with increasing maternal ages. This study indicated that NIPT detection in elderly pregnant women has an excellent application value in clinical practice to reduce the incidence of birth defects and abortion caused by invasive chromosome examination.


Asunto(s)
Enfermedades Fetales , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Anciano , Adulto , Edad Materna , Diagnóstico Prenatal/métodos , Aneuploidia , Aberraciones Cromosómicas , Enfermedades Fetales/diagnóstico , Cariotipo , Trisomía
9.
Mol Neurobiol ; 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38066400

RESUMEN

Spinal cord injury (SCI) is a serious disabling central nervous system injury that can lead to motor, sensory, and autonomic dysfunction below the injury level. SCI can be divided into primary injury and secondary injury according to pathological process. Primary injury is mostly irreversible, while secondary injury is a dynamic regulatory process. Apoptosis is an important pathological event of secondary injury and has a significant effect on the recovery of nerve function after SCI. Nerve cell death can further aggravate the microenvironment of the injured site, leading to neurological dysfunction and thus affect the clinical outcome of patients. Therefore, apoptosis plays a crucial role in the pathological progression of secondary SCI, while inhibiting apoptosis may be a promising therapeutic strategy for SCI. This review will summarize and explore the factors that lead to cell death after SCI, the influence of cross talk between signaling pathways and pathways involved in apoptosis and discuss the influence of apoptosis on SCI, and the therapeutic significance of targeting apoptosis on SCI. This review helps us to understand the role of apoptosis in secondary SCI and provides a theoretical basis for the treatment of SCI based on apoptosis.

10.
Medicine (Baltimore) ; 102(44): e34683, 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37933071

RESUMEN

To explore the potential mechanism of Gegen Qinlian decoction (GGQL) in the treatment of COVID-19 comorbid with diabetes mellitus (DM) through network pharmacology and molecular docking, and to provide theoretical guidance for clinical transformation research. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to screen the active compounds and targets of GGQL, the targets of COVID-19 comorbid with DM were searched based on Genecards database. Protein-protein interaction network was constructed using String data platform for the intersection of compounds and disease targets, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the intersection targets was performed using DAVID database. Cytoscape software was used to construct the "compound target-pathway (C-T-P)" of GGQL in the treatment of COVID-19 comorbid with DM, the molecular docking platform was used to complete the simulated docking of key compounds and targets. We obtained 141 compounds from GGQL, revealed 127 bioactive compounds and 283 potential targets of GGQL. Quercetin, kaempferol and formononetin in GGQL play a role by modulating the targets (including AR, GSK3B, DPP4, F2, and NOS3). GGQL might affect diverse signaling pathways related to the pathogenesis of coronavirus disease - COVID-19, AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, human cytomegalovirus infection and Th17 cell differentiation. Meanwhile, molecular docking showed that the selected GGQL core active components had strong binding activity with the key targets. This study revealed that GGQL play a role in the treatment of COVID-19 comorbid with DM through multi-component, multi-target and multi-pathway mode of action, which provided good theoretical basis for further verification research.


Asunto(s)
COVID-19 , Diabetes Mellitus , Medicamentos Herbarios Chinos , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Medicina Tradicional China
11.
Zhongguo Gu Shang ; 36(10): 954-8, 2023 Oct 25.
Artículo en Chino | MEDLINE | ID: mdl-37881928

RESUMEN

OBJECTIVE: To evaluate the short-term efficacy of proximal fibula osteotomy in the treatment of knee osteoarthritis, and to analyze the effect of osteotomy on the tension of the lateral knee soft tissue of patients and verify the reliability of the Arch string theory. METHODS: A total of 71 patients with varus knee osteoarthritis from December 2019 to March 2022 were included, 3 patients dropped out, and 68 patients completed all trials, collected 27 males and 41 females, aged from 51 to 79 years old, with an average of (68.0±7.0 ) years old. The follow-up time ranged from 4 to 12 weeks, with an average of (3.76±1.94) weeks. After admission, the patient underwent Proximal fibula osteotomy, and the tension of lateral knee soft tissue, visual analogue scale (VAS) of pain, the western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and other indicators were recorded before surgery and 1 month after surgery in the weight-bearing state. RESULTS: According to the VAS, the curative effect of a single index was evaluated by referring to the score before and after treatment by Bao Zongzhao. Thirty seven cases were markedly effective, 27 cases were effective, and 4 cases were ineffective. After surgery, 3 patients presented with weakness of dorsalis pedis extension and 1 presented with paresthesia of dorsalis pedis, which disappeared after symptomatic treatment . The VAS and WOMAC score at 1 month after operation were lower than those before operation, and the differences were statistically significant(P<0.001). The tension of lateral knee soft tissue 1 month after operation was lower than that before operation, and the difference had statistical significance(P<0.001). CONCLUSION: Proximal fibula osteotomy is safe and effective in the treatment of varus knee osteoarthritis in the short term. One month after osteotomy, the tension of lateral knee soft tissue increases under weight-bearing state, but the long-term changes still need further observation and follow-up.


Asunto(s)
Osteoartritis de la Rodilla , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Osteoartritis de la Rodilla/cirugía , Peroné/cirugía , Reproducibilidad de los Resultados , Tibia/cirugía , Articulación de la Rodilla/cirugía , Osteotomía , Resultado del Tratamiento , Estudios Retrospectivos
12.
Discov Oncol ; 14(1): 148, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37566174

RESUMEN

OBJECTIVE TERT: is the most frequently mutated gene in adult glioblastomas (GBMs) defined by the 2021 World Health Organization classification system. The present study aims to explore differences in clinical characteristics and immune microenvironment between TERT mutant and wild-type GBM. METHODS: Three GBM-related cohorts consisting of 205 GBM patients in our cohort, 463 GBM patients without immune checkpoint inhibitor(ICI) therapy and 1465 tumour patients (including 92 GBM cases) receiving ICI treatment in the MSK cohort were included. Retrospective analysis and immunohistochemistry assay were used for investigating the local (including tumour cells, local immune cells, and seizures) and systemic (including circulating immune cells, coagulation-related functions, and prognosis) effects of TERT mutations. Besides, differences in genetic alterations and immunotherapy responses between TERT mutant and wild-type GBMs were also explored. RESULTS: We found that TERT mutant and wild-type GBMs possessed similar initial clinic symptoms, circulating immune microenvironment and immunotherapy response. With respect to that in TERT wild-type GBMs, mutations in TERT resulted in higher levels of tumour-infiltrating neutrophils, prolonged coagulation time, worse chemotherapy response and poorer overall survival. CONCLUSION: Mutations in TERT alter the local immune environment and decrease the sensitivity of GBM to chemotherapy.

13.
Front Pharmacol ; 14: 1243243, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37637420

RESUMEN

Background: Ketosis is one of the most frequent and costly metabolic disorders in high-producing dairy cows, and negatively associated with the health and reproductive performance of bovine. Ketosis is mainly caused by the accumulation of ketone body ß-hydroxybutyric acid and its diagnosis is based on ß-hydroxybutyrate (ßHB) concentration in blood. Methods: In this study, we investigated the effects of ßHB on bovine oocyte maturation in the concentration of subclinical (1.2 mM) ßHB and clinical (3.6 mM). Results: The results showed ßHB disrupted bovine oocyte maturation and development capacity. Further analysis showed that ßHB induced oxidative stress and mitochondrial dysfunction, as indicated by the increased level of reactive oxygen species (ROS), disrupted mitochondrial structure and distribution, and depolarized membrane potential. Furthermore, oxidative stress triggered early apoptosis, as shown by the enhanced levels of Caspase-3 and Annexin-V. Moreover, 3.6 mM ßHB induced the disruption of the pyruvate dehydrogenase (PDH) activity, showing with the decrease of the global acetylation modification and the increase of the abnormal spindle rate. Conclusion: Our study showed that ßHB in subclinical/clinical concentration had toxic effects on mitochondrial function and PDH activity, which might affect energy metabolism and epigenetic modification of bovine oocytes and embryos.

14.
Int Immunopharmacol ; 123: 110761, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37544025

RESUMEN

Astrocytes are crucially involved in neuroinflammation. Activated astrocytes exhibit at least two phenotypes, A1 (neurotoxic) and A2 (neuroprotective). The A1 phenotype is the major reactive astrocyte phenotype involved in aging and neurodegenerative diseases. Telmisartan, which is an antihypertensive agent, is a promising neuroprotective agent. This study aimed to investigate the effects of telmisartan on the phenotype of reactive astrocytes. Astrocytes were activated by culturing with the conditioned medium derived from lipopolysaccharide-stimulated microglia. This conditioned medium induced early, transient A2 astrocyte conversion (within 24 h) and late, sustained A1 conversion (beginning at 24 h and lasting up to 7 days), with a concomitant increase in the production of pro-inflammatory cytokines (interleukin [IL]-1ß, tumor necrosis factor [TNF]α, and IL-6) and phosphorylation of nuclear factor-κB (NF-κB)/p65. Telmisartan treatment promoted and inhibited A2 and A1 conversion, respectively. Telmisartan reduced total and phosphorylated p65 protein levels. Losartan, a specific angiotensin II type-1 receptor (AT1R) blocker, did not influence the reactive state of astrocytes. Additionally, AT1R activation by angiotensin II did not induce the expression of pro-inflammatory cytokines and A1/A2 markers, indicating that the AT1R signaling pathway is not involved in the astrocyte-mediated inflammatory response. A peroxisome proliferator-activated receptor γ (PPARγ) antagonist reversed the effects of telmisartan. Moreover, telmisartan-induced p65 downregulation was reversed by the proteasome inhibitor MG132. These results indicate that telmisartan suppresses activated microglia-induced neurotoxic A1 astrocyte conversion through p65 degradation. Our findings contribute towards the elucidation of the anti-inflammatory activity of telmisartan in brain disorders.


Asunto(s)
FN-kappa B , PPAR gamma , Telmisartán/farmacología , FN-kappa B/metabolismo , PPAR gamma/metabolismo , Astrocitos/metabolismo , Microglía , Angiotensina II/metabolismo , Medios de Cultivo Condicionados/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
15.
Zool Res ; 44(5): 837-847, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37501399

RESUMEN

The common marmoset ( Callithrix jacchus) has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies. Epileptic marmosets have been independently reported in two Asian primate research centers. Nevertheless, the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated. Here, we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing. We identified 14 558 184 single nucleotide polymorphisms (SNPs) from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples. Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers. In addition, SNP and copy number variation (CNV) analyses suggested that the WW domain-containing oxidoreductase ( WWOX) and Tyrosine-protein phosphatase nonreceptor type 21 ( PTPN21) genes may be associated with epilepsy in marmosets. Notably, KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets. This study provides valuable population genomic resources for marmosets in two Asian primate centers. Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers, while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.


Asunto(s)
Callithrix , Epilepsia , Animales , Callithrix/genética , Estudios de Casos y Controles , Variaciones en el Número de Copia de ADN , Genética de Población , Epilepsia/veterinaria
16.
Drug Des Devel Ther ; 17: 2183-2192, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37521036

RESUMEN

Introduction: Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of Lactobacillus rhamnosus GG (LGG) in relieving intestinal mucosal injury induced by TMZ. Methods: Glioblastoma mice were divided into four groups: CON (control), LGG (109 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1ß, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKß, IκBα, and P65 with their phosphorylation in jejunum were measured. Results: Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos-IKKß and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group. Conclusion: LGG inhibits the activation of the TLR4-NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.


Asunto(s)
Probióticos , Receptor Toll-Like 4 , Animales , Ratones , Receptor Toll-Like 4/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Quinasa I-kappa B/metabolismo , Mucosa Intestinal/metabolismo , Transducción de Señal , Proteínas de Uniones Estrechas/metabolismo
17.
Front Endocrinol (Lausanne) ; 14: 1217669, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37497349

RESUMEN

Osteosarcoma is a highly aggressive and metastatic malignant tumor. It has the highest incidence of all malignant bone tumors and is one of the most common solid tumors in children and adolescents. Osteosarcoma tissues are often richly infiltrated with inflammatory cells, including tumor-associated macrophages, lymphocytes, and dendritic cells, forming a complex immune microenvironment. The expression of immune checkpoint molecules is also high in osteosarcoma tissues, which may be involved in the mechanism of anti-tumor immune escape. Metabolism and senescence are closely related to the immune microenvironment, and disturbances in metabolism and senescence may have important effects on the immune microenvironment, thereby affecting immune cell function and immune responses. Metabolic modulation and anti-senescence therapy are gaining the attention of researchers as emerging immunotherapeutic strategies for tumors. Through an in-depth study of the interconnection of metabolism and anti- senescence in the tumor immune microenvironment and its regulatory mechanism on immune cell function and immune response, more precise therapeutic strategies can be developed. Combined with the screening and application of biomarkers, personalized treatment can be achieved to improve therapeutic efficacy and provide a scientific basis for clinical decision-making. Metabolic modulation and anti- senescence therapy can also be combined with other immunotherapy approaches, such as immune checkpoint inhibitors and tumor vaccines, to form a multi-level and multi-dimensional immunotherapy strategy, thus further enhancing the effect of immunotherapy. Multidisciplinary cooperation and integrated treatment can optimize the treatment plan and maximize the survival rate and quality of life of patients. Future research and clinical practice will further advance this field, promising more effective treatment options for patients with osteosarcoma. In this review, we reviewed metabolic and senescence characteristics in the immune microenvironment of osteosarcoma and related immunotherapies, and provide a reference for development of more personalized and effective therapeutic strategies.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Niño , Humanos , Adolescente , Calidad de Vida , Inmunoterapia/métodos , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/patología , Microambiente Tumoral
19.
Gene ; 877: 147569, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37330022

RESUMEN

In recent years, the use of microbes to control termites has attracted increasing attention. It was found that pathogenic bacteria, nematodes, and fungi effectively control termites under laboratory conditions. However, their effects have not been replicated in the field, and one reason for this is the complex immune defense mechanisms of termites, which are mainly regulated by immune genes. Therefore, altering the expression of immune genes may have a positive influence on the biocontrol efficacy of termites. Coptotermes formosanus Shiraki is one of the most economically important termite pests worldwide. Currently, the large-scale identification of immune genes in C. formosanus is primarily based on cDNA library or transcriptome data rather than at the genomic level. In this study, we identified the immune genes of C. formosanus according to genome-wide analysis. In addition, our transcriptome analysis showed that immune genes were significantly downregulated when C. formosanus was exposed to the fungus Metarhizium anisopliae or nematodes. Finally, we found that injecting dsRNA to inhibit three immune genes (CfPGRP-SC1, CfSCRB3, and CfHemocytin), which recognize infectious microbes, significantly increased the lethal effect of M. anisopliae on termites. These immune genes show great potential for C. formosanus management based on RNAi. These results also increase the number of known immune genes in C. formosanus which will provide a more comprehensive insight into the molecular basis of immunity in termites.


Asunto(s)
Isópteros , Metarhizium , Animales , Isópteros/genética , Isópteros/microbiología , Metarhizium/genética , Perfilación de la Expresión Génica
20.
Medicine (Baltimore) ; 102(20): e33830, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37335714

RESUMEN

Tumor treating fields (TTFields) is a novel approved modality for the treatment of glioblastoma (GBM) exhibiting a satisfactory effect. Although TTFields has shown considerable safety for the normal brain, dermatological adverse events (DAEs) often occur during therapy. However, studies focused on the identification and management of DAEs are rare. The clinical data and photos of skin lesions from 9 patients with GBM were retrospectively analyzed, and the types and grades of individual scalp dermatitis were evaluated based on the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0). Adherence and safety were also evaluated on the basis of the device monitoring data. Eight patients (88.9%) exhibited grade 1 or grade 2 CTCAE DAEs, all of whom were cured after interventions. The adherence was >90%, with no relevant safety events reported. Finally, a guideline for preventing DAEs in patients with GBM was proposed. The identification and management of TTFields-related DAEs is necessary and urgent in patients with GBM. Timely interventions of DAEs will help to improve the adherence and quality of life of patients, which ultimately improves prognosis. The proposed guideline for preventing DAEs in patients with GBM assists in the management of healthcare providers and may avoid dermatologic complications.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Enfermedades de la Piel , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Glioblastoma/complicaciones , Glioblastoma/terapia , Estudios Retrospectivos , Enfermedades de la Piel/epidemiología , Enfermedades de la Piel/prevención & control
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