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1.
Mediators Inflamm ; 2024: 4777789, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39502754

RESUMEN

Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine-choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR)-mediated autophagy and ferroptosis markers, such as p-AMPKα/AMPKα, p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Autofagia , Ferroptosis , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Serina-Treonina Quinasas TOR , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Ferroptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Masculino , Proteínas Quinasas Activadas por AMP/metabolismo , Transducción de Señal/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico
2.
Front Endocrinol (Lausanne) ; 15: 1433026, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39483976

RESUMEN

Background: The pivotal responsibility of GABAergic interneurons is inhibitory neurotransmission; in this way, their significance lies in regulating the maintenance of excitation/inhibition (E/I) balance in cortical circuits. An abundance of glucocorticoids (GCs) exposure results in a disorder of GABAergic interneurons in the prefrontal cortex (PFC); the relationship between this status and an enhanced vulnerability to neuropsychiatric ailments, like depression and anxiety, has been identified, but this connection is still poorly understood because systematic and comprehensive research is lacking. Here, we aim to investigate the impact of dexamethasone (DEX, a GC receptor agonist) on GABAergic interneurons in the PFC of eight-week-old adult male mice. Methods: A double-blind study was conducted where thirty-two mice were treated subcutaneously either saline or DEX (0.2 mg/10 ml per kg of body weight) dissolved in saline daily for 21 days. Weight measurements were taken at five-day intervals to assess the emotional changes in mice as well as the response to DEX treatment. Following the 21-day regimen of DEX injections, mice underwent examinations for depression/anxiety-like behaviours and GABAergic marker expression in PFC. Results: In a depression/anxiety model generated by chronic DEX treatment, we found that our DEX procedure did trigger depression/anxiety-like behaviors in mice. Furthermore, DEX treatment reduced the expression levels of a GABA-synthesizing enzyme (GAD67), Reelin, calcium-binding proteins (parvalbumin and calretinin) and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y and vasoactive intestinal peptide) in the PFC were reduced after 21 days of DEX treatment; these reductions were accompanied by decreases in brain size and cerebral cortex thickness. Conclusion: Our results indicate that a reduction in the number of GABAergic interneurons may result in deficiencies in cortical inhibitory neurotransmission, potentially causing an E/I imbalance in the PFC; this insight suggests a potential breakthrough strategy for the treatment of depression and anxiety.


Asunto(s)
Ansiedad , Depresión , Dexametasona , Modelos Animales de Enfermedad , Neuronas GABAérgicas , Corteza Prefrontal , Proteína Reelina , Animales , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Masculino , Ratones , Dexametasona/farmacología , Depresión/metabolismo , Depresión/inducido químicamente , Ansiedad/metabolismo , Ansiedad/inducido químicamente , Neuronas GABAérgicas/metabolismo , Neuronas GABAérgicas/efectos de los fármacos , Método Doble Ciego , Interneuronas/metabolismo , Interneuronas/efectos de los fármacos , Glucocorticoides/farmacología , Biomarcadores/metabolismo , Ratones Endogámicos C57BL , Glutamato Descarboxilasa/metabolismo
3.
Hum Vaccin Immunother ; 20(1): 2408852, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39434209

RESUMEN

Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment, and the associated immune-related adverse events (irAEs) have garnered significant attention, yet reports on associated immune related gastritis are limited. The diagnosis of immune related gastritis remains predominantly exclusionary, meanwhile its management diverges significantly from that of conventional gastritis. Current guidelines lack standardized grading criteria, and substantial data from large-scale, tertiary clinical studies are absent, therefore we conducted a systematic review of Medline, Web of Science, and Embase databases, identifying 31 articles from 2017 to December 31, 2023, involving 258 patients. Clinical manifestations included epigastric pain (53.1%), mucosal erythema (56.1%), and lymphocyte infiltration (48.6%). Corticosteroid therapy was common (94.7%), with 86.7% experiencing post-treatment improvement. 80% of patients can be diagnosed through endoscopy and pathology, while the remaining 20% may require PET-CT. Hormonal therapy is favored but diverges from standard management. Accurate diagnosis is crucial in managing immune related gastritis effectively.


Asunto(s)
Gastritis , Inhibidores de Puntos de Control Inmunológico , Humanos , Gastritis/inmunología , Gastritis/diagnóstico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos
4.
EClinicalMedicine ; 76: 102836, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39364270

RESUMEN

Background: Neoadjuvant chemotherapy (NACT) is commonly used to downstage the tumor in locally advanced colon cancer (LACC) and improve the R0 resection rate. Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal and esophageal cancers, but its benefits in LACC remain poorly understood. This study aimed to compare the effects and safety of NACRT and NACT on R0 resection and survival rates in initially unresectable LACC. Methods: This was an open-label, single-center, randomized, controlled trial conducted between May 11, 2019 and May 30, 2022. Forty-five patients with initially unresectable LACC were randomly allocated to the NACT (control, n = 20) or NACRT (research, n = 25) group. The NACT group received XELOX (oxaliplatin 100-130 mg/m2, qd, d1, every 3 weeks; and capecitabine 1000 mg/m2, bid, d1-d14, every 3 weeks) for 4 cycles. The NACRT group, in addition to chemotherapy, received daily irradiation (GTV 45-50 Gy/25 F; CTV 42.5-45 Gy/25 F). Surgery was scheduled 6-12 weeks after neoadjuvant treatment and adjuvant chemotherapy was administered if the patient developed resectable LACC. The primary endpoint was the 5-year overall survival (OS) rate. The secondary outcomes included the 3-year progression-free survival (PFS) and R0 resection rates. This study was registered with ClinicalTrials.gov (NCT03970694). Findings: In short-term outcome analysis, NACRT significantly improved the R0 resection rate (80% for NACRT vs. 20% for NACT, P < 0.001). The NACRT and NACT groups had a 3-year OS of 87.6% and 75% (P = 0.037) and a 3-year PFS of 76% and 45% (P = 0.049), respectively. The 5-year OS was not reached. In the NACRT group, no local or regional recurrence was observed in patients who underwent surgery during the follow-up period, compared to two patients in the NACT group. Both NACT and NACRT were well tolerated, with no significant differences in severe adverse events. The most commonly observed grade 3-4 AE was myelosuppression (39% for NACRT and 47% for NACT, P = 0.609). No grade 5 AEs were observed between the two groups. Interpretation: Adding radiation to NACT increased the R0 resection rate, prolonged the PFS, and potentially improved OS in selected patients with initially unresectable LACC. The trial findings indicate that this approach is safe, feasible, and may confer a survival benefit. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373213 to Dr Gao, 82202952 to Dr Wang); and the Natural Science Foundation of Guangdong Province (2023A1515010290 to Dr Chang). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.

5.
Medicine (Baltimore) ; 103(42): e40040, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39432617

RESUMEN

BACKGROUND: The aim of this study was to evaluate the impact of health Qigong on vascular elasticity, blood lipid levels, and cardiac function in middle-aged and elderly women. By comparing various indicators preintervention and postintervention, the research provides valuable insights into the effectiveness of health Qigong in enhancing cardiovascular health within this demographic. METHODS: A total of 40 middle-aged and elderly women were randomly assigned to 2 groups. The experimental group, consisting of 20 women, practiced health Qigong combined with Tibetan dance for 12 weeks, 3 times per week, with each session lasting 60 minutes. The control group, also consisting of 20 women, continued their regular routines without any exercise intervention. Cardiovascular function metrics were subsequently compared between the 2 groups. RESULTS: (1) Pulse wave velocity: in the experimental group, significant improvements were observed, particularly in the right ankle (P =.02 for left ankle, P =.00 for right ankle). The control group showed no significant differences (P =.08 for both ankles); (2) blood lipid levels: the experimental group demonstrated significant reductions in total cholesterol and triglyceride levels (P =.00 for both), while the control group showed no significant changes (P =.59 for total cholesterol, P =.71 for triglycerides). There were significant differences in high-density lipoprotein levels between the experimental and control groups (P =.00 and .01, respectively); (3) cardiac function: significant improvements were noted in cardiac output (Teich) and stroke volume (Teich) in the experimental group (P =.00 for both), while the control group showed no significant differences (P =.71 for cardiac output, P =.06 for stroke volume). CONCLUSION: Health Qigong, integrated with dance exercise effectively enhances pulse wave velocity, blood lipid levels, and cardiac function in middle-aged and elderly women. These findings suggest that incorporating such exercises may contribute to the prevention or delay of atherosclerosis and cardiovascular disease in this population.


Asunto(s)
Análisis de la Onda del Pulso , Qigong , Humanos , Femenino , Qigong/métodos , Persona de Mediana Edad , Anciano , Lípidos/sangre , Baile/fisiología , Rigidez Vascular/fisiología
6.
SAGE Open Med Case Rep ; 12: 2050313X241286680, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39376550

RESUMEN

Nasal myiasis is a nasal infestation caused by myiasis, a parasitic disease affecting the nasal cavity. It is a rare condition. The nasal cavity is in close proximity to the sinuses, eyes, and cranial cavity. If the fly larvae migrate into this location, it may result in significant complications. The prompt and appropriate removal of maggots and the administration of an efficacious treatment can effectively prevent further deterioration of the disease. In this case study, we present the case of a 55-year-old woman who was admitted to the intensive care unit with severe respiratory failure. On the fourth day following admission, the patient remained unconscious, and several white larvae emerged from the nasal cavity. Through identification, the larvae were determined to be Musca domestica larvae. Subsequently, saline irrigation was performed under nasal endoscopy, and anti-inflammatory therapy was administered to the patient to prevent intracranial infection. Following treatment, the patient's symptoms were effectively managed, and the prognosis remained favorable until the 1-month follow-up. This case report presents a literature review of the reported cases of nasal myiasis caused by M. domestica and discusses the susceptibility factors and treatment modalities for nasal myiasis.

7.
Adv Sci (Weinh) ; : e2410354, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39473357

RESUMEN

The discovery of nanoscale ferroelectricity in hafnia (HfO2) has paved the way for next generation high-density, non-volatile devices. Although the surface conditions of nanoscale HfO2 present one of the fundamental mechanism origins, the impact of external environment on HfO2 ferroelectricity remains unknown. In this study, the deleterious effect of ambient moisture is examined on the stability of ferroelectricity using Hf0.5Zr0.5O2 (HZO) films as a model system. It is found that the development of an intrinsic electric field due to the adsorption of atmospheric water molecules onto the film's surface significantly impairs the properties of domain retention and polarization stability. Nonetheless, vacuum heating efficiently counteracts the adverse effects of water adsorption, which restores the symmetric electrical characteristics and polarization stability. This work furnishes a novel perspective on previous extensive studies, demonstrating significant impact of surface water on HfO2-based ferroelectrics, and establishes the design paradigm for the future evolution of HfO2-based multifunctional electronic devices.

8.
Int J Mol Sci ; 25(20)2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39456893

RESUMEN

Nonalcoholic steatohepatitis (NASH) is a form of chronic liver disease that is characterized by liver inflammation and steatosis, with possible progression to fibrosis. Currently, no drugs have been approved for the treatment of NASH. In this study, we isolated a polysaccharide from Atractylodes lancea rhizome (AP) and established a methionine- and choline-deficient (MCD) diet -induced NASH mouse model to investigate the preventive effect and potential mechanism of AP on NASH. The results showed that AP effectively reduced liver lipid accumulation and inflammation and reduced autophagy and ferroptosis in hepatocytes, thereby preventing the development of NASH. These findings suggest that AP may be a promising natural candidate for the treatment of NASH.


Asunto(s)
Atractylodes , Enfermedad del Hígado Graso no Alcohólico , Polisacáridos , Rizoma , Transducción de Señal , Serina-Treonina Quinasas TOR , Proteína p53 Supresora de Tumor , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Polisacáridos/química , Atractylodes/química , Rizoma/química , Ratones , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Proteína p53 Supresora de Tumor/metabolismo , Modelos Animales de Enfermedad , Metionina/deficiencia , Ratones Endogámicos C57BL , Autofagia/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Ferroptosis/efectos de los fármacos , Dieta , Deficiencia de Colina/complicaciones
9.
Int J Mol Sci ; 25(19)2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39409181

RESUMEN

Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (Scd1), Spermine Synthase (Sms), AP-1 Transcription Factor Subunit (Fos), Oxysterol Binding Protein Like 5 (Osbpl5), and FK506 binding protein 5 (Fkbp5) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Ácido Gálico , Metabolismo de los Lípidos , Hígado , Enfermedad del Hígado Graso no Alcohólico , Estearoil-CoA Desaturasa , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Animales , Ratones , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacología , Estearoil-CoA Desaturasa/metabolismo , Estearoil-CoA Desaturasa/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Dieta Alta en Grasa/efectos adversos , Lipogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
10.
Clin Lab ; 70(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39257108

RESUMEN

BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of ˃ 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.


Asunto(s)
Anticuerpos Antinucleares , Anticuerpos Monoclonales Humanizados , ADN , Humanos , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , ADN/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Persona de Mediana Edad , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Artritis Reumatoide/sangre , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Adulto , Biomarcadores/sangre
11.
J Cancer ; 15(16): 5308-5317, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247596

RESUMEN

Tellurium is a rare element, and ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) is the most bioactive molecule among several synthetic tellurium compounds. AS101 was found to be immunomodulatory and can modulate types of cytokines. However, the effect of AS101 on tumor metastasis remains unclear. Heparanase, an endo-glucuronidase, cleaves heparin sulfate side chains of proteoglycans on the cell surface, further leading to the degradation of the extracellular matrix. Heparanase also releases angiogenic factors in the extracellular matrix, is overexpressed in tumor cells, and promotes tumor metastasis and angiogenesis. In this study, we investigated the effect of AS101 in 4T1 and CT26 cells, especially heparanase. Heparanase expression was downregulated in 4T1 and CT26 cells after treatment with AS101 in vitro. The protein level involved in the protein kinase-B/mammalian target of rapamycin (AKT/mTOR) signaling pathway also declined. Cell migration assays revealed the inhibitory effect of AS101 on migration. The results of this study indicate that AS101 inhibits tumor migration by downregulating heparanase through the AKT/mTOR signaling pathway and has positive effects in vivo.

12.
Front Neurosci ; 18: 1415008, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280262

RESUMEN

Background: Many systematic reviews (SRs) have reported the efficacy of acupuncture in improving Parkinson's disease (PD), but the quality of evidence is unknown. Therefore, it is necessary to comprehensively summarize and objectively evaluate the evidence of acupuncture for PD. Methods: Seven databases were searched to retrieve SRs on the acupuncture for PD. Two reviewers independently completed literature retrieval, screening, and data extraction. The methodological quality, risk of bias (RoB), evidence quality of the included SRs were assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2), the Risk of Bias in Systematic Reviews (ROBIS), the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Results: A total of 24 SRs were included. According to AMSTAR 2, 6 (25%) were rated as high quality, 6 (25%) were rated as moderate quality, and 12 (50%) were rated as very low quality. The application of the ROBIS tool showed that 12 (25%) SRs were at low risk of bias. The results of GRADE showed that 8 (7.62%) outcomes provided high quality evidence, 23 (21.9%) outcomes provided moderate quality evidence, 42 (40%) outcomes provided low quality evidence, and 32 (30.48%) outcomes provided very low quality evidence. Conclusion: The overview indicates that acupuncture shows promise as a treatment for PD, although the evidence is limited and inconclusive due to methodological flaws and the heterogeneity of existing studies. Future research should focus on fully reporting methodological details and following review guidelines to produce more reliable and consistent evidence on the effectiveness of acupuncture for PD. Systematic review registration: https://inplasy.com, identifier INPLASY202480049.

13.
Drug Dev Res ; 85(6): e22254, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39234934

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. Syncytin-1 (Syn), an envelope glycoprotein encoded by the env gene of the human endogenous retrovirus-W family, has been resorted to be highly expressed in biopsies from the muscles from ALS patients; however, the specific regulatory role of Syn during ALS progression remains uncovered. In this study, C57BL/6 mice were injected with adeno-associated virus-overexpressing Syn, with or without Fasudil administration. The Syn expression was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry analysis. The histological change of anterior tibial muscles was determined by hematoxylin-eosin staining. Qualitative ultrastructural analysis of electron micrographs obtained from lumbar spinal cords was carried out. Serum inflammatory cytokines were assessed by enzyme linked immunosorbent assay (ELISA) assay and motor function was recorded using Basso, Beattie, and Bresnahan (BBB) scoring, climbing test and treadmill running test. Immunofluorescence and western blot assays were conducted to examine microglial- and motor neurons-related proteins. Syn overexpression significantly caused systemic inflammatory response, muscle tissue lesions, and motor dysfunction in mice. Meanwhile, Syn overexpression promoted the impairment of motor neuron, evidenced by the damaged structure of the neurons and reduced expression of microtubule-associated protein 2, HB9, neuronal nuclei and neuron-specific enolase in Syn-induced mice. In addition, Syn overexpression greatly promoted the expression of CD16/CD32 and inducible nitric oxide synthase (M1 phenotype markers), and reduced the expression of CD206 and arginase 1 (M2 phenotype markers). Importantly, the above changes caused by Syn overexpression were partly abolished by Fasudil administration. This study provides evidence that Syn-activated microglia plays a pivotal role during the progression of ALS.


Asunto(s)
1-(5-Isoquinolinesulfonil)-2-Metilpiperazina , Ratones Endogámicos C57BL , Microglía , Neuronas Motoras , Animales , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/metabolismo , Ratones , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Productos del Gen env , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/metabolismo , Proteínas Gestacionales/metabolismo , Masculino , Citocinas/metabolismo , Modelos Animales de Enfermedad , Actividad Motora/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos
14.
Antioxidants (Basel) ; 13(9)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39334685

RESUMEN

Nonalcoholic steatohepatitis (NASH) is a critical stage in the progression of nonalcoholic fatty liver disease (NAFLD). Tanshinone IIA (TIIA) is a tanshinone extracted from Salvia miltiorrhiza; due to its powerful anti-inflammatory and antioxidant biological activities, it is commonly used for treating cardiovascular and hepatic diseases. A NASH model was established by feeding mice a methionine and choline-deficient (MCD) diet. Liver surface microblood flow scanning, biochemical examination, histopathological examination, cytokine analysis through ELISA, lipidomic analysis, transcriptomic analysis, and Western blot analysis were used to evaluate the therapeutic effect and mechanism of TIIA on NASH. The results showed that TIIA effectively reduced lipid accumulation, fibrosis, and inflammation and alleviated endoplasmic reticulum (ER) stress. Lipidomic analysis revealed that TIIA normalized liver phospholipid metabolism in NASH mice. A KEGG analysis of the transcriptome revealed that TIIA exerted its effect by regulating the PPAR signalling pathway, protein processing in the ER, and the NOD-like receptor signalling pathway. These results suggest that TIIA alleviates NASH by activating the PPARα/FGF21 axis to negatively regulate the ER stress-induced unfolded protein response (UPR).

15.
Front Oncol ; 14: 1389278, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301548

RESUMEN

Background: Lymphovascular invasion (LVI) is a significant risk factor for lymph node metastasis in gastric cancer (GC) and is closely related to the prognosis and recurrence of GC. This study aimed to establish clinical models, radiomics models and combination models for the diagnosis of GC vascular invasion. Methods: This study enrolled 146 patients with GC proved by pathology and who underwent radical resection of GC. The patients were assigned to the training and validation cohorts. A total of 1,702 radiomic features were extracted from contrast-enhanced computed tomography images of GC. Logistic regression analyses were performed to establish a clinical model, a radiomics model and a combined model. The performance of the predictive models was measured by the receiver operating characteristic (ROC) curve. Results: In the training cohort, the age of LVI negative (-) patients and LVI positive (+) patients were 62.41 ± 8.41 and 63.76 ± 10.08 years, respectively, and there were more male (n = 63) than female (n = 19) patients in the LVI (+) group. Diameter and differentiation were the independent risk factors for determining LVI (-) and (+). A combined model was found to be relatively highly discriminative based on the area under the ROC curve for both the training (0.853, 95% CI: 0.784-0.920, sensitivity: 0.650 and specificity: 0.907) and the validation cohorts (0.742, 95% CI: 0.559-0.925, sensitivity: 0.736 and specificity: 0.700). Conclusions: The combined model had the highest diagnostic effectiveness, and the nomogram established by this model had good performance. It can provide a reliable prediction method for individual treatment of LVI in GC before surgery.

16.
Int J Biometeorol ; 68(11): 2307-2319, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39105775

RESUMEN

Long time series of vegetation monitoring can be carried out by remote sensing data, the level of urban greening is objectively described, and the spatial characteristics of plant pollen are indirectly understood. Pollen is the main allergen in patients with seasonal allergic rhinitis. Meteorological factors affect the release and diffusion of pollen. Therefore, studying of the complex relationship between meteorological factors and allergic rhinitis is essential for effective prevention and treatment of the disease. In this study, we leverage remote sensing data for a comprehensive decade-long analysis of urban greening in Tianjin, which exhibits an annual increase in vegetative cover of 0.51 per annum, focusing on its impact on allergic rhinitis through changes in pollen distribution. Utilizing high-resolution imagery, we quantify changes in urban Fractional Vegetation Coverage (FVC) and its correlation with pollen types and allergic rhinitis cases. Our analysis reveals a significant correlation between FVC trends and pollen concentrations, with a surprising value of 0.71, highlighting the influence of urban greenery on allergenic pollen levels. We establish a robust connection between the seasonal patterns of pollen outbreaks and allergic rhinitis consultations, with a noticeable increase in consultations during high pollen seasons. our findings indicate a higher allergenic potential of herbaceous compared to woody vegetation. This nuanced understanding underscores the importance of pollen sensitivity, alongside concentration, in driving allergic rhinitis incidents. Utilizing a Generalized Linear Model, significant features influencing the number of visits for allergic rhinitis (P < 0.05) were identified. Both GLM and LSTM models were employed to forecast the visitation volumes for rhinitis during the spring and summer-autumn of 2022. Upon validation, it was found that the R² values between the simulated and actual values for both GLM and LSTM models surpassed the 95% confidence threshold. Moreover, the R² values for the summer-autumn seasons (GLM: 0.56, LSTM: 0.72) were higher than those for spring (GLM: 0.22, LSTM: 0.47). Comparing the errors between the simulated and actual values of GLM and LSTM models, LSTM exhibited higher simulation precision in both spring and summer-autumn seasons, demonstrating superior simulation performance. Overall, our study pioneers the integration of remote sensing with meteorological and health data for allergic rhinitis forecasting. This integrative approach provides valuable insights for public health planning, particularly in urban settings, and lays the groundwork for advanced, location-specific allergenic pollen forecasting and mitigation strategies.


Asunto(s)
Alérgenos , Predicción , Polen , Tecnología de Sensores Remotos , Rinitis Alérgica , China/epidemiología , Humanos , Rinitis Alérgica/epidemiología , Alérgenos/análisis , Tiempo (Meteorología) , Ciudades/epidemiología , Rinitis Alérgica Estacional/epidemiología , Conceptos Meteorológicos , Estaciones del Año
17.
Sci Rep ; 14(1): 19167, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160247

RESUMEN

Faults play a crucial role in shaping the formation and damage patterns of landslides in the mountainous region, particularly in Qinling-Daba (Qinba) area in China. On 6 October 2022, following a 4-day rainfall event totaling 221.5 mm, a landslide occurred in Hanwang Town, Shaanxi Province. The left boundary of the landslide coincided with a fault, which influence the formation and movement development of the landslide. To further understand and quantified the formation process and damage mechanism of the landslide, a comprehensive study was conducted, incorporating field investigations, local rainfall data, and various methods including unmanned aerial vehicles (UAVs), numerical simulations, and laboratory test. The results indicate that fault dictate the formation of the Lijiaping landslide by influencing the mechanical strength of the rock mass and the catchment topography in the landslide area. Due to fault, the rock mass in the landslide area is high fragmentation, with a softening coefficient of about 0.52. Weathering resulted in numerous residual and slope sediments in the landslide area, providing ample material for the landslide. Meanwhile, the fault activity led to a wedge-shaped topography in the landslide area, with an average Terrain Wetness Index (TWI) of 3.43, significantly higher than the Hanwang Township average of 1.47. This creates a hydrogeological structure favorable for landslides. Numerical simulations revealed that the maximum velocity of the landslide reached 5.05 m/s and the maximum displacement was 53.18 m, both occurring in the central part of the landslide. These findings offer crucial scientific insights for understanding and preventing similar geological hazards.

18.
Sci Rep ; 14(1): 18402, 2024 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-39117753

RESUMEN

Gaining a comprehensive understanding of the role played by the oral microbiome in moderate to severe plaque psoriasis and its potential implications for disease management and development holds significant importance. With the objective of exploring correlations between the oral microbiota and severe psoriasis, this study involved 72 severe psoriasis patients and 16 healthy individuals, whose clinical manifestations and living habits were carefully recorded. Cutting-edge techniques such as 16S rRNA gene sequencing and bioinformatics analysis were employed to compare the microbial flora, investigating dynamic changes among severe plaque psoriasis patients, psoriatic arthritis patients and healthy individuals. The findings revealed noteworthy patterns including increased levels of Aggregatibacter in the psoriatic arthritis group, accompanied by a decrease in the level of Prevotella. Moreover, the enrichment o Capnocytandophaga (P = 0.009), Campylobacter (P = 0.0022), and Acetobacter (P = 0.0292) was notably more substantial in the psoriasis group compared to the control group, whereas certain bacterial species such as Bacteroides (P = 0.0049), Muribaculaceae (P = 0.0048) demonstrated decreased enrichment. Additionally, the psoriatic arthritis group exhibited significantly higher levels of Ralstonia, Bifidobacterium and Micromonospora. Based on these findings, it can be inferred that individuals with lower levels of Prevotella and higher levels of Corynebacterium may be more susceptible to psoriasis exacerbation.


Asunto(s)
Artritis Psoriásica , Microbiota , Psoriasis , ARN Ribosómico 16S , Humanos , Artritis Psoriásica/microbiología , Femenino , Masculino , Psoriasis/microbiología , Microbiota/genética , Adulto , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Boca/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Enfermedades de la Uña/microbiología , Estudios de Casos y Controles
20.
World J Clin Oncol ; 15(8): 1110-1116, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39193160

RESUMEN

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is a malignant tumor that originates from the lymphoid tissues and can potentially affect numerous organs within the body. Among these, the skin stands out as one of the primary sites affected by NHL, often presenting with multiple extra-nodal manifestations. In this report, we present an unusual case of NHL involving chronic wounds in the lower extremities that were difficult to heal. The scars were successfully treated using radiotherapy in combination with extended excision debridement and peroneal artery perforator flap grafting, resulting in satisfactory outcomes. CASE SUMMARY: A 19-year-old male patient presented with ulceration of the skin on the left calf near the ankle accompanied by purulent discharge. Subsequent pathologic biopsy confirmed a diagnosis of NHL (extranodal NK/T-cell lymphoma, nasal type). Initial treatment comprised local radiotherapy and wound care; however, the wound exhibited prolonged non-healing. Consequently, the patient underwent a series of interventions including radiotherapy, wound enlargement excision debridement, and peroneal artery perforator flap grafting. Ultimately, successful healing was achieved with favorable postoperative outcomes characterized by good texture of the flap without any signs of rupture or infection. CONCLUSION: The combination of radiotherapy, wound enlargement excision debridement, and peroneal artery perforator flap grafting may present a favorable treatment modality for chronic non-healing lower leg wounds resulting from NHL.

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