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1.
Exp Neurol ; 382: 114961, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39288829

RESUMO

Intracerebral hemorrhage, is a cerebrovascular disease with high morbidity, mortality, and disability. Due to the lack of effective clinical treatments, the development of new drugs to treat intracerebral hemorrhage is necessary. In recent years, ferroptosis has been found to play an important role in the pathophysiological process of intracerebral hemorrhage, which can be treated by inhibiting ferroptosis and thus intracerebral hemorrhage. This article aims to explain the mechanism of ferroptosis and its relationship to intracerebral hemorrhage. In the meantime, it briefly discusses the molecules identified to alleviate intracerebral hemorrhage by inhibiting ferroptosis, along with other clinical agents that are expected to treat intracerebral hemorrhage through this mechanism. In addition, a brief overview of the morphological alterations of different forms of cell death and their role in ICH is provided. Finally, the challenges that may arise in translating ferroptosis inhibitors from basic research to clinical use are presented. This article serves as a reference and provides insights to aid in the treatment of intracerebral hemorrhage in the clinic.

2.
BMC Psychol ; 12(1): 508, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334285

RESUMO

BACKGROUND: Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children's quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. METHODS: This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. DISCUSSION: This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. TRIAL REGISTRATION: This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.


Assuntos
Adaptação Psicológica , Neoplasias do Sistema Nervoso Central , Medo , Qualidade de Vida , Humanos , Medo/psicologia , Criança , Qualidade de Vida/psicologia , Neoplasias do Sistema Nervoso Central/psicologia , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Ansiedade/psicologia , Masculino , Manejo da Dor/métodos , Pré-Escolar , Adolescente , Ensaios Clínicos Controlados Aleatórios como Assunto , Ludoterapia/métodos
3.
Int J Biol Macromol ; 279(Pt 3): 135407, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245108

RESUMO

Two polysaccharides, PGP-90 and PGP-100 (molecular weights of 7.59 × 102 kDa and 10.48 × 102 kDa, respectively), were isolated from Peach gum using alkaline electrolyte water as an extraction solution. Structural characterization showed that PGP-90 and PGP-100 are AG-II arabinogalactans with ß-D-(1 â†’ 6)-Galp as the main chain and 1 â†’ 3 Araf and 1 â†’ 5 Araf branched chains at O-3 and O-4 positions. Animal experiments showed that PGP-90 and PGP-100 significantly improved immune function, enhance the proliferative capacity of lymphocytes and phagocytosis of peritoneal macrophages, and regulated the ratio of lymphocyte subpopulations in S180 tumor-bearing mice. Meanwhile, PGP-90 and PGP-100 promoted the secretion of cytokines (TNF-α, IFN-γ, and IL-2) by activated macrophages and blocked apoptosis at the G1 phase, resulting in tumor suppression rates of 40.80 % and 46.30 % (100 mg/kg), respectively, with PGP-100 demonstrating stronger in vivo anti-tumor activity. The above experimental results indicate that Peach gum polysaccharides have the potential to be functional anti-tumor agents.

4.
Int J Biol Macromol ; 278(Pt 2): 134784, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39151863

RESUMO

Six Cordyceps militaris polysaccharides (named CMP-1, CMP-2, CMP-3, CMP-4, CMP-9, and CMP-A) were obtained by fractional alcohol precipitation. The experimental results showed that the six Cordyceps militaris polysaccharides had similar chemical composition and spectral features, and different molecular weights, monosaccharide compositions and anti-tumor activities. Purification of CMP-9 yielded the small molecule polysaccharide LMW-CMP (3.06 kDa). Structural experiments showed that LMW-CMP is an α-glucan with (1 â†’ 4)-α-D-Glcp as the main chain and a glucose branched chain attached at the O-6 position. The results of cell experiments showed that LMW-CMP could effectively inhibit the growth and proliferation of HepG2 cells, activate the downstream NF-κB signaling pathway through the MAPK pathway to induce apoptosis of HepG2 cells, and block apoptosis at the G1 phase. Animal experiments showed that LMW-CMP inhibited the proliferation of tumor cells in H22 tumor-bearing mice by improving the state of immune organs, increasing the activity of immune cells and cytokine levels in the body, and regulating the distribution of lymphocyte subpopulations, with a tumor inhibition rate of 45.70 % (200 mg/kg).


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Cordyceps , Etanol , Polissacarídeos Fúngicos , Cordyceps/química , Animais , Humanos , Camundongos , Etanol/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Peso Molecular , NF-kappa B/metabolismo , Monossacarídeos/análise
5.
Zhongguo Zhen Jiu ; 44(6): 689-93, 2024 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-38867632

RESUMO

The paper introduces JIAO Lin's clinical experience in treatment of knee osteoarthritis (KOA) by manual mobilization of meridian muscle regions. Professor JIAO Lin believes that the key to the occurrence and development of KOA lies in the disorder of meridian muscle regions (sinews/fascia). In pathology, four stages are divided, i.e. the acute stage, the blockage stage, the contraction stage and the atrophy stage of muscle regions, characterized as multi-layer, multi-dimensional and multi-morphological distribution. In treatment, based on the principle, "taking pain sites as stimulating points", the sites, with reduced pain threshold and distributed along the meridian muscle regions, are regarded as "acupoints" for intervention. Manual mobilization of meridian muscle regions is the dominant approach, combined with routine acupuncture, heat-sensitive moxibustion, cupping and bloodletting corresponding to the features of syndromes and meridian manifestation at different stages. The comprehensive treatment may restore and reconstruct the physiological functions of the meridian muscle regions around knee joints by "nourishing tendons, strengthening bones and benefiting joints".


Assuntos
Pontos de Acupuntura , Meridianos , Osteoartrite do Joelho , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia por Acupuntura , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/fisiopatologia
6.
Technol Health Care ; 32(S1): 385-402, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38759063

RESUMO

BACKGROUND: The purpose of this meta-analysis was to evaluate the effectiveness and safety of thoracic manipulation (TM) in patients with neck pain (NP). OBJECTIVE: The purpose of this meta-analysis was to evaluate the effectiveness and safety of thoracic manipulation (TM) in patients with neck pain (NP). METHODS: Seven electronic databases were searched from their inception through October 2023 by two authors. The methodological quality assessments were performed with the Physiotherapy Evidence Database (PEDro) scale. Pain, cervical range of motion (ROM), disability, and quality of life (QOL) were estimated for TM treatment in patients with NP. RESULTS: Eighteen randomized controlled trials (RCTs) with 914 patients were included with a PEDro score of 6.923 ± 3.120. Pooled effect sizes of pain (SMD =-0.481, 95% CI -0.653 to -0.309, P= 0.000), disability (SMD =-1.435, 95% CI -2.480 to -0.390, P= 0.007), QOL-physical component score (PCS) (SMD = 0.658, 95% CI 0.290 to 1.025, P= 0.000), ROM of flexion (SMD = 0.921, 95% CI 0.287 to 1.555, P= 0.000), ROM of extension (SMD = 0.572, 95% CI 0.321 to 0.822, P= 0.000), ROM of left lateral flexion (SMD = 0.593, 95% CI 0.075 to 1.112, P= 0.025) and ROM of left rotation (SMD = 0.230, 95% CI 0.010 to 0.450, P= 0.04) were favored by the TM group. CONCLUSIONS: TM provides short-term effect on relieving neck pain, increasing cervical ROM, and disability in patients with NP without serious side effects. Continuous therapy and distraction therapy are recommended as optimal choice on reducing pain and improving cervical ROM, especially in patients with chronic NP (> 3 months). The TM-induced improvements in the QOL of patients with NP should be verified by more further high-quality RCTs.


Assuntos
Cervicalgia , Qualidade de Vida , Amplitude de Movimento Articular , Humanos , Cervicalgia/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Manipulação da Coluna/métodos
7.
Int J Biol Macromol ; 269(Pt 1): 131812, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38670197

RESUMO

An important micronutrient involved in immune response and antitumor is selenium. LMW-GFP, a polysaccharide extracted from Grifola frondosa seed bodies, has a relatively weak antitumor effect on BGC-823 and MFC cells in vitro, whereas selenium binding to LMW-GFP can significantly increase the in vitro antitumor activity of LMW-GFP. In this study, Se-LMW-GFP was prepared by the HNO3-Na2SeO3 method, and the structures of LMW-GFP and Se-LMW-GFP were characterized by UV-visible spectroscopy of absorption, FTIR spectroscopy, and electron scanning microscopy, and these structural analyses showed that selenium was successfully complexed to LMW-GFP. The selenium content of Se-LMW-GFP was measured to be 2.08 % ± 0.08 % by ICP-MS. The anti-tumor activity of LMW-GFP before and after selenium modification was compared by cellular experiments, and the findings indicated that the anti-tumor activity of Se-LMW-GFP was considerably improved over that of LMW-GFP, and inhibited the proliferation of BGC-823 cells and MFC cells through a combination of the Fas/FasL-mediated exogenous death receptor pathway as well as the endogenous mitochondrial pathway. Our results suggest that Se-LMW-GFP not only has great potential for natural health food and anti-gastric cancer drug development but is also a good selenium supplement.


Assuntos
Proliferação de Células , Grifola , Peso Molecular , Selênio , Neoplasias Gástricas , Grifola/química , Humanos , Selênio/química , Selênio/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química
8.
Am J Ophthalmol ; 264: 154-161, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38556185

RESUMO

PURPOSE: To comprehensively identify the corneal biomechanical differences measured by Corvis ST between different degrees of myopia and emmetropia. DESIGN: Systematic review and meta-analysis. METHODS: Electronic databases, including PubMed, Embase, and Web of Science, were systematically searched for studies comparing the corneal biomechanics among various degrees of myopes and emmetropes using Corvis ST. The weighted mean differences and 95% confidence intervals were calculated. Meta-analysis was performed in high and nonhigh myopes and in myopes and emmetropes, respectively. RESULTS: Eleven studies were included in this study. The meta-analysis among myopes and emmetropes included 1947 myopes and 621 emmetropes, and 443 high myopes and 449 nonhigh myopes were included in the meta-analysis among high and nonhigh myopia. Myopes showed the cornea with significantly longer time at the first applanation (A1t) and lower length at the second applanation (A2L) than emmetropes. High myopes showed significantly greater A1t, velocity at the second applanation (A2v), deformation amplitude at the highest concavity (HC-DA), and peak distance at the highest concavity (HC-PD) and decreased time at the second applanation (A2t) and radius of the highest concavity (HC-R). CONCLUSIONS: Corneal biomechanics is different in myopia, especially in high myopia. Compared with nonhigh myopes, the corneas of high myopes deformed slower during the first applanation, faster during the second applanation, and showed greater deformation amplitude, indicating greater elasticity and viscidity.


Assuntos
Córnea , Emetropia , Miopia , Humanos , Córnea/fisiopatologia , Emetropia/fisiologia , Fenômenos Biomecânicos/fisiologia , Miopia/fisiopatologia , Elasticidade/fisiologia , Pressão Intraocular/fisiologia , Tonometria Ocular , Refração Ocular/fisiologia
9.
Clin Exp Rheumatol ; 42(5): 1035-1042, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38372719

RESUMO

OBJECTIVES: Rheumatic and musculoskeletal diseases (RMD) may exhibit different immune responses to novel coronavirus (COVID-19) infection compared to healthy individuals. While previous studies have primarily investigated changes in COVID-19-related antibodies post-vaccination for RMD patients, this study sought to explore the dynamics of SARS-CoV-2 IgG antibodies and neutralising antibodies (NAb) in RMD patients after COVID-19 infection. METHODS: In this longitudinal study, we monitored the SARS-CoV-2 IgG antibodies and NAb levels in RMD patients and healthy controls (HC) at 60 and 90 days post-COVID-19 infection. Chemiluminescent immunoassay was used to detect the levels of novel coronavirus-specific IgG (anti-S1/S2 IgG) antibodies and NAb. RESULTS: A total of 292 RMD patients and 104 HC were enrolled in the study. At both the 60-day and 90-day post-COVID-19 infection, RMD patients exhibited significantly lower levels of anti-S1/S2 IgG and NAb than those in the HC group (p<0.001). The anti-S1/S2 IgG antibody levels remained relatively stable, while the NAb levels in RMD patients could vary greatly between the 60th and 90th days. A logistic regression analysis revealed that the prior administration of glucocorticoids (GC), immunosuppressants, and b/tsDMARDs stood out as independent risk factors associated with reduced anti-S1/S2 IgG and NAb levels, irrespective of the specific RMD subtypes. CONCLUSIONS: GC and anti-rheumatic medications can potentially alter the production of specific antibodies, especially NAb, in RMD patients post-COVID-19 infection. These findings emphasise the importance of continuous monitoring for NAb fluctuations in RMD patients following a COVID-19 infection.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Imunoglobulina G , Doenças Musculoesqueléticas , Doenças Reumáticas , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/sangue , Doenças Reumáticas/imunologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Estudos Longitudinais , Adulto , Doenças Musculoesqueléticas/imunologia , Doenças Musculoesqueléticas/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Idoso , Estudos de Casos e Controles
10.
Neurochem Res ; 49(4): 815-833, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38170383

RESUMO

Ischemic stroke is a common neurological disease. Currently, there are no Food and Drug Administration-approved drugs that can maximize the improvement in ischemic stroke-induced nerve damage. Hence, treating ischemic stroke remains a clinical challenge. Ferroptosis has been increasingly studied in recent years, and it is closely related to the pathophysiological process of ischemic stroke. Iron overload, reactive oxygen species accumulation, lipid peroxidation, and glutamate accumulation associated with ferroptosis are all present in ischemic stroke. This article focuses on describing the relationship between ferroptosis and ischemic stroke and summarizes the relevant substances that ameliorate ischemic stroke-induced neurological damage by inhibiting ferroptosis. Finally, the problems in the treatment of ischemic stroke targeting ferroptosis are discussed, hoping to provide a new direction for its treatment.


Assuntos
Ferroptose , Sobrecarga de Ferro , AVC Isquêmico , Humanos , Ácido Glutâmico , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio
11.
J Glaucoma ; 32(11): 954-961, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37671508

RESUMO

PRCIS: There was a significant inverse linear relationship between age at menopause and open angle glaucoma (OAG). Late menarche (≥13 y) and a history of 5 or more deliveries were significantly associated with an increased risk of OAG. PURPOSE: To determine the association between reproductive factors including age at menarche, age at menopause, reproductive period, parity, and the risk of OAG in women. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched until February 9, 2022. Studies were included if they assessed the association between reproductive factors and OAG. The adjusted odds ratios (ORs) with relevant 95% CIs were extracted and pooled using fixed-effects models. Besides, we conducted dose-response analyses via the generalized least squares for trend method. RESULTS: Seven articles including 18,618 women were identified in this review. The pooled results indicated that late age at menarche (≥13 y) was significantly associated with an increased risk of OAG (OR=1.76, 95% CI: 1.28, 2.43). Early menopause (<45 y) also significantly elevated the risk of OAG (OR=1.89, 95% CI: 1.23, 2.90) in categorical meta-analyses, consistent with the inverse linear relationship between menopausal age and the risk of OAG in dose-response analyses ( P =0.002). In addition, women who had delivered at least 5 children were at significantly higher risk of OAG compared with those nulliparous (OR=2.35, 95% CI: 1.02, 5.39), and a J-shape relationship between parity and OAG was observed in dose-response analyses ( P <0.001). CONCLUSIONS: Late menarche (≥13 y), early menopause (<45 y), and a history of 5 or more parturitions are possible risk factors for OAG. Longitudinal studies are warranted to further examine the relationships between reproductive factors and the risk of OAG.


Assuntos
Glaucoma de Ângulo Aberto , Gravidez , Criança , Feminino , Humanos , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/epidemiologia , Glaucoma de Ângulo Aberto/etiologia , Pressão Intraocular , História Reprodutiva , Paridade , Menopausa/fisiologia , Fatores de Risco
12.
J Immunother Cancer ; 11(9)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37734878

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises. Identification of ways to prevent the emergence of cancer in high-risk patients is an ultimate goal for combatting all types of cancer, including OSCC. METHODS: Our study employs a mouse model of tongue carcinogenesis induced by tobacco carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), to establish tongue dysplasia and OSCC. We use conventional histology, immunohistochemistry, multispectral imaging, mass cytometry, novel cell lines, pharmaceutical inhibition of PI3Kγ, T-cell suppression assays and mouse transplant models in our functional experimentation. RESULTS: In our study, we identify Ly6G+ granulocytes as the most abundant immune cell type in a model of tongue carcinogenesis induced by tobacco carcinogen mimetic 4NQO. Targeting Ly6G+ granulocytes with a pharmacologic inhibitor of PI3Kγ, an isoform of PI3K exclusively expressed by myeloid cells, resulted in reduced tongue dysplasia severity, and reduced rates of OSCC. Importantly, we performed functional assays with the Ly6G+ granulocytes induced in cell line models of 4NQO carcinogenesis to demonstrate that these granulocytes have increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) activity against T-cell proliferation and these PMN-MDSCs play a functional role in promoting tumor formation by inhibiting tumor regression in a PI3Kγ-dependent manner. CONCLUSIONS: Overall, our data suggest that recruitment of PMN-MDSCs to sites of dysplasia is critical to immune suppression of CD8 T cells, thereby permitting malignancy, and PI3Kγ inhibitors are one mechanism to reduce PMN-MDSC recruitment, immunosuppression and tumorigenesis in OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Células Supressoras Mieloides , Humanos , Animais , Camundongos , Fosfatidilinositol 3-Quinase , Carcinoma de Células Escamosas/induzido quimicamente , Neoplasias Bucais/induzido quimicamente , Carcinogênese , Carcinógenos/toxicidade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fosfatidilinositóis
13.
Cancer Lett ; 570: 216330, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37524225

RESUMO

Transforming growth factor beta (TGFß) activity is linked to metastasis in many cancer types, but whether TGFß activity is necessary for squamous cell carcinoma (SCC) lung metastasis has not been studied. Here we used a lung metastatic SCC model derived from keratin 15 (K15). KrasG12D.Smad4-/- SCC and human SCC specimens to identify metastasis drivers and test therapeutic interventions. We demonstrated that a TGFß receptor (TGFßR) inhibitor reduced lung metastasis in mouse SCC correlating with reduced CD11b+/Ly6G+ myeloid cells positive for inducible nitric oxide synthase (iNOS). Further, TGFß activity and iNOS were higher in primary human oral SCCs with metastasis than SCCs without metastasis. Consistently, either depleting myeloid cells with anti-Gr1 antibody or inhibiting iNOS with L-N6-(1-iminoethyl)-l-lysine (L-NIL) reduced SCC lung metastasis. L-NIL treated tumor-bearing mice exhibited reductions in tumor-infiltrating myeloid cells and in plasma Cxcl5 levels, and attenuated primary tumor growth with increased apoptosis and decreased proliferation. Blocking Cxcl5 with an antagonist of its receptor Cxcr2, SB225002, also reduced SCC lung metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Óxido Nítrico Sintase Tipo II , Fator de Crescimento Transformador beta/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/metabolismo , Células Mieloides/metabolismo , Óxido Nítrico/metabolismo
14.
Pharm Biol ; 61(1): 839-857, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37203204

RESUMO

CONTEXT: Current chemotherapeutic drugs cannot meet the treatment needs of patients with nasopharyngeal carcinoma (NPC), so urgent action is needed to discover novel chemotherapeutic agents. Our previous study revealed that garcinone E (GE) inhibited the proliferation and metastasis of NPC, suggesting that the compound might display promising anticancer activity. OBJECTIVE: To examine the mechanism underlying the anti-NPC activity of GE for the first time. MATERIALS AND METHODS: For MTS assay, NPC cells were treated with 2.5-20 µmol/L GE or dimethyl sulfoxide for 24, 48, and 72 h. Colony formation capacity, cell cycle distribution, and in vivo xenograft experiment of GE were assessed. MDC staining, StubRFP-sensGFP-LC3 observation, LysoBrite Blue staining, and immunofluorescence examined the autophagy of NPC cells after GE exposure. Western blotting, RNA-sequencing, and RT-qPCR measured protein and mRNA levels. RESULTS: GE suppressed cell viability with an IC50 of 7.64, 8.83 and 4.65 µmol/L for HK1, HONE1 and S18 cells. GE inhibited colony formation and cell cycle, increased autophagosome number, and inhibited the autophagic flux partially by blocking lysosome-autophagosome fusion, and repressed S18 xenograft growth. GE dysregulated the expression of autophagy- and cell cycle-related proteins such as Beclin-1, SQSTM1/p62, LC3, CDKs, and Cyclins. Bioinformatics GO and KEGG pathway enrichment analysis of RNA-seq showed that autophagy was enriched in differentially expressed genes upon GE treatment. DISCUSSION AND CONCLUSION: GE acts as an autophagic flux inhibitor, which may have potential chemotherapeutic use for NPC treatment and may have an application in basic research to explore the mechanisms of autophagy.


Assuntos
Apoptose , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Proliferação de Células , Autofagia , Linhagem Celular Tumoral , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia
15.
J Invest Dermatol ; 143(11): 2243-2254.e10, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37211203

RESUMO

Long-term management of inflammatory skin diseases is challenging because of side effects from repeated use of systemic treatments or topical corticosteroids. This study sought to identify the mechanisms and developmental therapeutics for these diseases using genetic models and pharmacological approaches. We found that mice overexpressing SMAD7 in keratinocytes but not mice overexpressing the N-terminal domain of SMAD7 (i.e., N-SMAD7) were resistant to imiquimod-induced T helper 1/17- and T helper 2-type inflammation. We generated a Tat-PYC-SMAD7 (truncated SMAD7 protein encompassing C-terminal SMAD7 and PY motif fused with cell-penetrating Tat peptide). Topically applied Tat-PYC-SMAD7 to inflamed skin entered cells upon contact and attenuated imiquimod-, 2,4-dinitrofluorobenzene-, and tape-stripping-induced inflammation. RNA-sequencing analyses of mouse skin exposed to these insults showed that in addition to inhibiting TGFß/NF-κB, SMAD7 blunted IL-22/signal transducer and activator of transcription 3 activation and associated pathogenesis, which is due to SMAD7 transcriptionally upregulating IL-22 antagonist IL-22RA2. Mechanistically, SMAD7 facilitated nuclear translocation and DNA binding of C/EBPß to IL22RA2 promoter for IL22RA2 transactivation. Consistent with the observations in mice mentioned earlier, transcript levels of IL22RA2 were increased in human atopic dermatitis and psoriasis lesions with clinical remission. Our study identified the anti-inflammation functional domain of SMAD7 and suggests the mechanism and feasibility for developing SMAD7-based biologics as a topical therapy for skin inflammatory disorders.


Assuntos
Dermatite , Psoríase , Receptores de Interleucina , Camundongos , Humanos , Animais , Imiquimode/farmacologia , Proteína Smad7/genética , Pele/patologia , Psoríase/tratamento farmacológico , Psoríase/genética , Psoríase/induzido quimicamente , Dermatite/patologia , Queratinócitos/metabolismo , Inflamação/patologia , Fenótipo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(4): 401-407, 2023 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-37073846

RESUMO

A boy, aged 16 months, attended the hospital due to head and facial erythema for 15 months and vulva erythema for 10 months with aggravation for 5 days. The boy developed perioral and periocular erythema in the neonatal period and had erythema and papules with desquamation and erosion in the neck, armpit, and trigone of vulva in infancy. Blood gas analysis showed metabolic acidosis; the analysis of amino acid and acylcarnitine profiles for inherited metabolic diseases and the analysis of organic acid in urine suggested multiple carboxylase deficiency; genetic testing showed a homozygous mutation of c.1522C>T(p.R508W) in the HLCS gene. Finally the boy was diagnosed with holocarboxylase synthetase deficiency and achieved a good clinical outcome after oral biotin treatment. This article analyzes the clinical data of a child with holocarboxylase synthetase deficiency and summarizes the etiology, diagnosis, and treatment of this child, so as to provide ideas for clinicians to diagnose this rare disease.


Assuntos
Deficiência de Holocarboxilase Sintetase , Humanos , Masculino , Biotina/genética , Biotina/uso terapêutico , Deficiência de Holocarboxilase Sintetase/genética , Deficiência de Holocarboxilase Sintetase/diagnóstico , Deficiência de Holocarboxilase Sintetase/tratamento farmacológico , Homozigoto , Mutação , Doenças Raras/tratamento farmacológico , Lactente
17.
Bioorg Chem ; 131: 106304, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36463590

RESUMO

Velvet antler is a traditional Chinese medicine with various pharmacological values, which is an important raw material for traditional Chinese medicinal wine. Nevertheless, the chemical compositions and bioactivities of velvet antler residue used for making medicinal wine are rarely reported, leading to a waste of resources. In this study, a velvet antler protein (VA-pro) was extracted from velvet antler residue by simulating the gastrointestinal digestion, and its composition, structural characteristics and in vivo anti-tumor activities were determined and investigated. VA-pro possessed high purity with a relatively low molecular weight as 22.589 kDa under HPLC, one- and two-dimensional electrophoresis, and it contained high contents of Pro, Gly, Glu and Ala. Besides, the secondary structure of VA-pro was dominated by ß-turn and ß-sheet, and VA-pro possessed similar protein sequence, isoelectric point and amino acid compositions to hypothetical protein G4228_020061. The in vivo results substantiated that VA-pro could improve the body weights and immune organ indices, increase the expressions of sera cytokines and regulate the distributions of T and B lymphocytes subsets in peripheral blood of S180 tumor-bearing mice. Furthermore, VA-pro could effectively inhibit solid S180 tumors growth by inducing S phase cell cycle arrest mediated through mitochondria. To summarize, our study provided theoretical support that VA-pro had the potential to be used as an immunopotentiator in immunocompromised or cancer-bearing hosts.


Assuntos
Chifres de Veado , Neoplasias , Camundongos , Animais , Chifres de Veado/química , Chifres de Veado/metabolismo , Peso Molecular , Proteínas/metabolismo , Aminoácidos/metabolismo , Neoplasias/metabolismo
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-971081

RESUMO

Biogenetics plays an important role in the pathogenesis of depressive disorder in adolescents. Various genetic polymorphism studies have updated the understanding of adolescent depressive disorder. However, due to the influence of gene-environment interaction and age of puberty, the influence of gene polymorphisms on adolescent depressive disorder is complicated to clarify. Investigating and clarifying the relationship between gene polymorphisms and adolescent depressive disorder will promote the research on the pathogenesis of this disorder and provide a reference for the prevention and treatment of this disorder. This article reviews the genetic polymorphisms related to adolescent depressive disorder.


Assuntos
Humanos , Adolescente , Transtorno Depressivo Maior/genética , Polimorfismo Genético , Interação Gene-Ambiente , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981970

RESUMO

A boy, aged 16 months, attended the hospital due to head and facial erythema for 15 months and vulva erythema for 10 months with aggravation for 5 days. The boy developed perioral and periocular erythema in the neonatal period and had erythema and papules with desquamation and erosion in the neck, armpit, and trigone of vulva in infancy. Blood gas analysis showed metabolic acidosis; the analysis of amino acid and acylcarnitine profiles for inherited metabolic diseases and the analysis of organic acid in urine suggested multiple carboxylase deficiency; genetic testing showed a homozygous mutation of c.1522C>T(p.R508W) in the HLCS gene. Finally the boy was diagnosed with holocarboxylase synthetase deficiency and achieved a good clinical outcome after oral biotin treatment. This article analyzes the clinical data of a child with holocarboxylase synthetase deficiency and summarizes the etiology, diagnosis, and treatment of this child, so as to provide ideas for clinicians to diagnose this rare disease.


Assuntos
Humanos , Masculino , Lactente , Biotina/uso terapêutico , Deficiência de Holocarboxilase Sintetase/tratamento farmacológico , Homozigoto , Mutação , Doenças Raras/tratamento farmacológico
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-982008

RESUMO

Non-suicidal self-injury (NSSI) is becoming increasingly common in adolescents and seriously affects their physical and mental health, and it is also a major risk factor for suicide among adolescents. NSSI has now become a public health issue of general concern; however, the identification of cognitive dysfunction in NSSI is still based on neuropsychological cognitive assessment and subjective questionnaire assessment, with a lack of objective evaluation indicators. As a method for studying the cognitive neural mechanism of NSSI, electroencephalography is a reliable tool for finding objective biomarkers of NSSI. This article reviews the recent research on electrophysiology associated with cognitive dysfunction in adolescents with NSSI.


Assuntos
Humanos , Adolescente , Comportamento Autodestrutivo , Disfunção Cognitiva , Eletroencefalografia , Testes Neuropsicológicos , Fatores de Risco
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