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1.
Curr Dev Nutr ; 8(4): 102147, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38645881

RESUMO

Background: Infant formula in the United States contains abundant iron, raising health concerns about excess iron intake in early infancy. Objectives: Using a piglet model, we explored the impact of high iron fortification and prebiotic or synbiotic supplementation on iron homeostasis and trace mineral bioavailability. Methods: Twenty-four piglets were stratified and randomly assigned to treatments on postnatal day 2. Piglets were individually housed and received an iron-adequate milk diet (AI), a high-iron milk diet (HI), HI supplemented with 5% inulin (HI with a prebiotic [HIP]), or HIP with an oral gavage of Ligilactobacillus agilis YZ050, an inulin-fermenting strain, every third day (HI with synbiotic [HIS]). Milk was provided in 14 meals daily, mimicking formula feeding in infants. Fecal consistency score and body weight were recorded daily or every other day. Blood and feces were sampled weekly, and tissues collected on postnatal day 29. Data were analyzed using mixed model analysis of variance with repeated measures whenever necessary. Results: Diet did not affect growth. HI increased hemoglobin, hematocrit, and serum iron compared to AI. Despite marginal adequacy, AI upregulated iron transporter genes and maintained satisfactory iron status in most pigs. HI upregulated hepcidin gene expression in liver, caused pronounced tissue iron deposition, and markedly increased colonic and fecal iron. Inulin supplementation, regardless of L. agilis YZ050, not only attenuated hepatic iron overload but also decreased colonic and fecal iron without altering pH or the expression of iron regulatory genes. HI lowered zinc (Zn) and copper (Cu) in the duodenum and liver compared to AI, whereas HIP and HIS further decreased Zn and Cu in the liver and diminished colonic and fecal trace minerals. Conclusions: Early-infancy excessive iron fortification causes iron overload and compromises Zn and Cu absorption. Inulin decreases trace mineral absorption likely by enhancing gut peristalsis and stool frequency.

2.
Front Immunol ; 15: 1383343, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660312

RESUMO

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.


Assuntos
Antirreumáticos , Artrite Reumatoide , Hidroxicloroquina , Hiperpigmentação , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Idoso , Feminino , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Hiperpigmentação/induzido quimicamente , Hiperpigmentação/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Pele/patologia , Pele/efeitos dos fármacos
3.
Nutrition ; 122: 112399, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38493542

RESUMO

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.


Assuntos
Neoplasias , Neutrófilos , Masculino , Humanos , Feminino , Caquexia/etiologia , Estudos de Coortes , Força da Mão , Linfócitos , Prognóstico , Neoplasias/complicações , Estudos Retrospectivos
4.
Purinergic Signal ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470513

RESUMO

Studies have confirmed that P2 purinergic receptors (P2X receptors and P2Y receptors) expressed in gastric cancer (GC) cells and GC tissues and correlates with their function. Endogenous nucleotides including ATP, ADP, UTP, and UDP, as P2 purinergic receptors activators, participate in P2 purinergic signal transduction pathway. These activated P2 purinergic receptors regulate the progression of GC mainly by mediating ion channels and intracellular signal cascades. It is worth noting that there is a difference in the expression of P2 purinergic receptors in GC, which may play different roles in the progression of GC as a tumor promoting factor or a tumor suppressor factor. Among them, P2 × 7, P2Y2 and P2Y6 receptors have certain clinical significance in patients with GC and may be used as biological molecular markers for the prediction of patients with GC. Therefore, in this paper, we discuss the functional role of nucleotide / P2 purinergic receptors signal axis in regulating the progression of GC and that these P2 purinergic receptors may be used as potential molecular targets for the prevention and treatment of GC.

5.
Eur J Haematol ; 112(6): 964-974, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38388794

RESUMO

OBJECTIVES: This study assesses the clinical significance of additional cytogenetic abnormalities (ACAs) and/or the deletion of 3'CBFB (3'CBFBdel) resulting in unbalanced CBFB::MYH11 fusion in acute myeloid leukemia (AML) with inv (16)/t(16;16)/CBFB::MYH11. METHODS: We retrospectively evaluated the clinicopathologic features of 47 adult de novo AML with inv (16)/t(16;16)/CBFB::MYH11 fusion. There were 44 balanced and 3 unbalanced CBFB::MYH11 fusions. Given the low frequency of unbalanced cases, the latter group was combined with 19 published cases (N = 22) for statistic and meta-analysis. RESULTS: Both balanced and unbalanced cases were characterized by frequent ACAs (56.5% and 72.7%, respectively), with +8, +22, and del(7q) as the most frequent abnormalities. The unbalanced group tends to be younger individuals (p = .04) and is associated with a lower remission rate (p = .02), although the median overall survival (OS) was not statistically different (p = .2868). In the balanced group, "ACA" subgroup had higher mortality (p = .013) and shorter OS (p = .011), and patients with relapsed disease had a significantly shorter OS (p = .0011). Cox multivariate regression analysis confirmed that ACAs and history of disease relapse are independent risk factors, irrespective of disease relapse status. In the combined cohort, cases with ACAs had shorter OS than those with "Sole" abnormality (p = .0109). CONCLUSIONS: ACAs are independent high-risk factors in adult AML with inv (16)/t(16;16)/CBFB::MYH11 fusion and should be integrated for risk stratification in this disease. Larger studies are needed to assess the clinical significance of the unbalanced CBFB::MYH11 fusion resulting from the 3'CBFBdel.


Assuntos
Aberrações Cromossômicas , Inversão Cromossômica , Cromossomos Humanos Par 16 , Leucemia Mieloide Aguda , Proteínas de Fusão Oncogênica , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Idoso , Cromossomos Humanos Par 16/genética , Prognóstico , Estudos Retrospectivos , Adulto Jovem , Subunidade beta de Fator de Ligação ao Core/genética , Adolescente , Idoso de 80 Anos ou mais , Translocação Genética , Cadeias Pesadas de Miosina/genética
6.
Eur J Med Res ; 29(1): 103, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326905

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have been extensively investigated in the field of cancer, among which, lncRNA ladybird homeobox 2-antisense RNA 1 (LBX2-AS1) has been demonstrated to exert carcinogenic effects on a variety of malignancies. However, the biological functions of LBX2-AS1 in clear cell renal cell carcinoma (ccRCC) have not been explicitly elucidated. METHODS: Arraystar lncRNA chip and qRT-PCR verify the expression of LncRNA LBX2-AS1 in ccRCC. CCK-8 assay and cell cloning assay were used to assess the proliferative capacity of ccRCC cells. Migration abilities were quantified by scratch assay and transwell assay. Potential molecular signaling pathways were determined by high-throughput whole transcriptomics analysis. WB analysis was performed to validate the relationship between LBX2-AS1 and key molecules of mitophagy pathway. The effect of LBX2-AS1 on mitophagy was observed by laser confocal microscopy. Rescue experiments further validated the role of downstream gene FOXO3A in the LBX2-AS1 signaling pathway. Finally, the authentic effect of LBX2-AS1 was verified in vivo. RESULTS: LncRNA LBX2-AS1 was over expressed in ccRCC tissues and could enhance the proliferation and migration of ccRCC cells. Autophagic pathway was identified as a possible mechanism involved in the oncogenic effect of LBX2-AS1. Mitophagy levels were observed in LBX2-AS1 low-expressing cells through laser confocal microscopy. Knockdown of LBX2-AS1 significantly elevated mitophagy levels as observed using laser confocal microscopy and led to FOXOA3 decreasing in and BNIP3L and LC3 enrichment. Meanwhile, LBX2-AS1 knocking down dampened the proliferation of ccRCC cells in vivo.


Assuntos
Carcinoma de Células Renais , Proteínas de Homeodomínio , Neoplasias Renais , RNA Longo não Codificante , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/patologia , MicroRNAs , Mitofagia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo
7.
Arch Biochem Biophys ; 753: 109893, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309681

RESUMO

Adipose tissue-derived stem cells (ADSCs) are a kind of stem cells with multi-directional differentiation potential, which mainly restore tissue repair function and promote cell regeneration. It can be directionally differentiated into Schwann-like cells to promote the repair of peripheral nerve injury. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the repair of nerve injury, but the underlying mechanism remains unclear, which seriously limits its further application.The study aimed to identify the molecular mechanism by which overexpression of glial cell line-derived neurotrophic factor (GDNF) facilitates the differentiation of ADSCs into Schwann cells, enhancing nerve regeneration after injury. In vitro, ADSCs overexpressing GDNF for 48 h exhibited changes in their morphology, with 80% of the cells having two or more prominences. Compared with that of ADSCs, GDNF-ADSCs exhibited increased expression of the Schwann cell marker S100, nerve damage repair-related factors.ADSC cells in normal culture and ADSC cells were overexpressing GDNF(GDNF-ADSCs) were analysed using TMT-Based Proteomic Analysis and revealed a significantly higher expression of MTA1 in GDNF-ADSCs than in control ADSCs. Hes1 expression was significantly higher in GDNF-ADSCs than in ADSCs and decreased by MTA1 silencing, along with a simultaneous decrease in the expression of S100 and nerve damage repair factors. These findings indicate that GDNF promotes the differentiation of ADSCs into Schwann cells and induces factors that accelerate peripheral nerve damage repair.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial , Proteômica , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Regeneração Nervosa , Tecido Adiposo , Diferenciação Celular , Células de Schwann
8.
Anal Sci ; 40(4): 765-772, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38358582

RESUMO

As one of the most fundamental thiol compounds in the human body, cysteine (Cys) is involved in maintaining redox balance. Abnormal Cys levels can lead to various diseases. In this work, we successfully synthesized a fluorescent probe (CTBA) that can specifically detect Cys using acrylate as the reaction site, and CTBA has met the selectivity and anti-interference for Cys detection under optimized conditions. The linear range for Cys detection is between 0.05 and 100 µM and the detection limit is 0.0381 µM. Finally, this probe is used to detect the Cys content in three bovine serum samples and the test results are satisfactory.


Assuntos
Cisteína , Corantes Fluorescentes , Humanos , Corantes Fluorescentes/química , Cisteína/química , Células HeLa , Limite de Detecção , Espectrometria de Fluorescência/métodos
9.
BMC Complement Med Ther ; 24(1): 47, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245694

RESUMO

BACKGROUND: Leguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance. METHODS: The SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets - LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding. RESULTS: We obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc., Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells. CONCLUSIONS: Results of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.


Assuntos
Alcaloides , Neoplasias Pulmonares , Sophora , Neoplasias Pulmonares/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicina Tradicional Tibetana , Fosfatidilinositol 3-Quinases , Alcaloides/farmacologia
10.
Br J Surg ; 111(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38215239

RESUMO

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.


Assuntos
Laparoscopia , Levamisol/análogos & derivados , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Resultado do Tratamento , Estudos de Coortes , Neoplasias Gástricas/cirurgia , Gastrectomia , Pontuação de Propensão , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
11.
Mol Cancer Res ; 22(1): 94-103, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37756563

RESUMO

Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells. IMPLICATIONS: Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.


Assuntos
Leucemia Mieloide Aguda , Monoéster Fosfórico Hidrolases , Animais , Camundongos , Leucemia Mieloide Aguda/genética , Mutação , Monoéster Fosfórico Hidrolases/genética , Fosforilação , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais/genética
12.
Leuk Lymphoma ; 65(1): 26-36, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37794791

RESUMO

The MYC protooncogene plays a critical role in many cellular processes. MYC translocations are recurrent in large B-cell lymphomas (LBCLs) where they exhibit a negative effect on survival. Gain of MYC copies is also frequently identified; however, there is no consensus on the frequency and prognostic significance of MYC copy gains. We collected FISH data for MYC with reflex testing for BCL2 and BCL6 and IHC results at diagnosis for a cohort of 396 de novo and transformed LBCL cases and compared progression-free (PFS) and overall survival (OS) to determine the prognostic impact of extra MYC copies. The prevalence of cases with MYC copy number gain was 20.9%. PFS was shorter for patients with ≥5 MYC copies compared to controls (p = 0.0005, HR = 2.25). .MYC gain trended towards worse OS; patients with ≥7MYC copies had worse OS (p = 0.013), similar to patients with MYC translocations. We propose that MYC gain represents a dose-dependent prognostic factor for LBCLs.


Assuntos
Variações do Número de Cópias de DNA , Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Hibridização in Situ Fluorescente , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Translocação Genética , Proteínas Proto-Oncogênicas c-bcl-6/genética
13.
Phytochemistry ; 218: 113958, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154730

RESUMO

Six undescribed nordrimane sesquiterpene derivatives, salvirrane A-F (1-6), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Comprehensive spectral analysis and a quantum chemical calculation strategy were employed to determine their structures. These compounds represent four previously unreported nordrimane carbon skeletal types in Salvia genus, including 15-nor-drimane, 11,15-di-nor-drimane, 14,15-di-nor-drimane, and 11,14,15-tri-nor-drimane sesquiterpenes. All compounds were evaluated for their cytotoxic activities against several human cancer cell lines (A549, H460, Hep3B, MCF7, PC3, and HeLa). The results showed that 3 exhibited low activity against MCF7 cells (IC50,72.72 ± 6.95 µM) and moderate activity against HeLa cells (IC50, 9.80 ± 0.64 µM). Moreover, the EdU (5-ethynyl-2'-deoxyuridine) assay demonstrates that 3 displays dose-dependent efficacy in suppressing the proliferation of HeLa cells. Network pharmacology and molecular docking technology implied that 3 may potentially bind to Src (proto-oncogene tyrosine-protein kinase) to exert anti-proliferative activity.


Assuntos
Antineoplásicos , Sesquiterpenos Policíclicos , Salvia , Sesquiterpenos , Humanos , Células HeLa , Simulação de Acoplamento Molecular , Sesquiterpenos/química , Antineoplásicos/farmacologia , Salvia/química , Estrutura Molecular
14.
PLoS Genet ; 19(12): e1011084, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38157491

RESUMO

mDia formin proteins regulate the dynamics and organization of the cytoskeleton through their linear actin nucleation and polymerization activities. We previously showed that mDia1 deficiency leads to aberrant innate immune activation and induces myelodysplasia in a mouse model, and mDia2 regulates enucleation and cytokinesis of erythroblasts and the engraftment of hematopoietic stem and progenitor cells (HSPCs). However, whether and how mDia formins interplay and regulate hematopoiesis under physiological and stress conditions remains unknown. Here, we found that both mDia1 and mDia2 are required for HSPC regeneration under stress, such as serial plating, aging, and reconstitution after myeloid ablation. We showed that mDia1 and mDia2 form hetero-oligomers through the interactions between mDia1 GBD-DID and mDia2 DAD domains. Double knockout of mDia1 and mDia2 in hematopoietic cells synergistically impaired the filamentous actin network and serum response factor-involved transcriptional signaling, which led to declined HSPCs, severe anemia, and significant mortality in neonates and newborn mice. Our data demonstrate the potential roles of mDia hetero-oligomerization and their non-rodent functions in the regulation of HSPCs activity and orchestration of hematopoiesis.


Assuntos
Actinas , Proteínas de Transporte , Camundongos , Animais , Forminas/genética , Forminas/metabolismo , Actinas/genética , Actinas/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Citoesqueleto de Actina/metabolismo , Microtúbulos/metabolismo
15.
Front Pharmacol ; 14: 1277283, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954842

RESUMO

Lonicerae Japonicae Caulis is the aboveground stem part of the Lonicera Japonica Thunb, which belongs to the medicine food homology species in China. It has the effects of clearing away heat, toxic material, dredging wind and unblocking collaterals. Modern research shows that it contains various active metabolites and a wide range of pharmacological effects, which is of great research and clinical application value. It mainly contains organic acids, volatile oils, flavonoids, triterpenes, triterpene saponins and other active metabolites. Its pharmacological effects mainly include anti-inflammatory, antibacterial, antitumor, antioxidant, and repairing bone and soft tissue. Based on the literature reports in recent years, the active metabolites, pharmacological effects and mechanisms of Lonicerae Japonicae Caulis were sorted out and summarized. It lays a foundation for explaining the efficacy material basis and application value of Lonicerae Japonicae Caulis. It aims to provide a reference for the in-depth research, development and utilization of Lonicerae Japonicae Caulis.

16.
Pharmaceuticals (Basel) ; 16(10)2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37895865

RESUMO

Cancer is still one of the major factors threatening public health, with morbidity and mortality rates at the forefront of the world. Clinical drawbacks, such as high toxicity and side effects of drug therapy, and easy recurrence after surgery affect its therapeutic effect. Gas signaling molecules are essential in maintaining biological homeostasis and physiological functions as specific chemical substances for biological information transfer. In recent years, the physiological regulatory functions of gas molecules in the cancer process have been gradually revealed and have shown broad application prospects in tumor therapy. In this paper, standard gas therapies are classified and introduced. Taking H2, CO2, NO, CO, H2S, and SO2 gases as examples, the research progress and application of gas therapies in malignant tumors are mainly introduced in terms of biological characteristics, anticancer mechanisms, and treatment strategies. Finally, the problems and prospects for developing gases as anticancer drugs are outlined.

17.
Front Oncol ; 13: 1239962, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37681019

RESUMO

Background: Resection of a giant retroperitoneal liposarcoma is difficult and technically demanding, especially for large retroperitoneal tumors accompanied by a diaphragmatic hernia. Technically, the open abdominal approach can be time-consuming and difficult to perform, with possible intraoperative complications and other factors bringing psychological and physical difficulties to the patient. This study reports a safe and feasible approach for the complete resection of a large retroperitoneal tumor complicated by a diaphragmatic hernia. Methods: A 58-year-old male patient with persistent upper abdominal pain and distension was treated at a local hospital on 4 July 2022. Computed tomography showed a mixed-density mass on the right retroperitoneum, and liposarcoma was considered. On 6 July 2022, the patient was transferred to our hospital for further treatment. Computed tomography showed a mass with low-density fatty shadow in the right adrenal region. The boundary with the right adrenal gland was unclear. The mass was 102 mm × 74 mm, and the right lobe of the liver was compressed. Insufficiency of the right middle lobe of the liver was seen due to a right diaphragmatic hernia and left mediastinal deviation. We considered the traditional approach for tumor resection via laparotomy, but we opted to perform a comprehensive evaluation first. The tumor was close to the back of the right kidney and liver, causing the diaphragm to rise because of its proximity to these organs. Exposing the tumor through laparotomy would be difficult, making it challenging to remove. The patient had a diaphragmatic hernia and moderate pulmonary dysfunction; therefore, we decided to enter the abdomen through a thoracotomy of the ninth rib. Results: Using our technique, the tumor was easily visualized and completely removed in approximately 30 min. The intraoperative blood loss was 100 ml, and no postoperative bleeding, pneumothorax, intestinal fistula, infection, or other complications occurred. Conclusion: The transthoracic approach may be a safer and more feasible resection method than the traditional open approach for patients with giant retroperitoneal liposarcoma with a diaphragmatic hernia.

18.
Sci Total Environ ; 899: 166415, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37598956

RESUMO

Exposure to microplastics (MPs) and hydrophobic organic contaminants (HOCs) combined at high concentrations may induce adverse effects to aquatic organisms in laboratory-scale studies. To determine environmentally relevant concentrations of HOCs in MPs, it is essential to understand the occurrence of MP-affiliated HOCs in the aquatic environment. Here we report the occurrences of HOCs affiliated with polymer-specific floating MPs from 12 tributaries and three estuaries in the Pearl River Delta, South China. Target HOCs include nine synthetic musks (SMs), 14 ultraviolet adsorbents (UVAs), 15 polycyclic aromatic hydrocarbons (PAHs), eight polybrominated diphenyl ethers (PBDEs), and 14 polychlorinated biphenyls (PCBs). Average concentrations of MP-affiliated ∑9SM, ∑14UVA, ∑15PAH, ∑8PBDE, and ∑14PCB were 1790, 5550, 1090, 412, and 107 ng g-1, respectively. The average concentrations of HOCs affiliated with MPs of different polymer types were 9790, 7220, 72,500, and 55,800 ng g-1 for polyethylene (PE), polypropylene, polystyrene, and other MPs, respectively. As the concentration of PE was the highest among all MPs at the average concentration of 0.77 mg m-3, the monthly outflow of PE-affiliated HOCs accounted for the largest proportion (46 %) in the outflow of MP-affiliated HOCs (2.8 g) to the coastal ocean via three estuaries. These results suggest that HOCs were highly concentrated in MPs and varied among different chemicals and polymer types. Due to the differences of polymer characteristics and half-life of affiliated chemicals, future toxicology studies concerning exposure to these combined pollutants may need to specify polymer types and their affiliated chemicals.

19.
Front Neurosci ; 17: 1203915, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37539383

RESUMO

Autoimmune encephalitis, a class of encephalitis, is clinically characterized by multifocal or diffuse brain injury, including aberrant mental behavior, convulsions, and near-event memory impairment. In this article, we describe a female patient with autoimmune encephalitis who tested positive for leucine-rich glioma inactivated 1 (LGI1) antibodies and had hippocampal inflammatory edema in the lesion area. During the first 3 months of her illness, the patient primarily experienced memory loss, the onset of rigid twitching in her extremities that lasted for 1 min while in remission, and incontinence. After gamma globulin administration, methylprednisolone shock, and other symptomatic therapies during hospitalization, the patient's psychiatric symptoms and seizures improved considerably; however, she did not fully recover her memory. After receiving fire acupuncture for 6 months, the patient's understanding, orientation, and calculation skills improved considerably. Her memory and mental state were also improved at the follow-up visit. In this case, the use of fire acupuncture for the treatment of autoimmune encephalitis resulted in favorable outcomes with important benefits for conditions affecting the central nervous system; however, more convincing data are required to support the effectiveness of this treatment method.

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