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1.
Am J Alzheimers Dis Other Demen ; 39: 15333175241271910, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39365953

RESUMEN

OBJECTIVES: Neuropsychological test batteries, which accurately and comprehensively assess cognitive functions, are a crucial approach in the early detection of and interventions for cognitive impairments. However, these tests have yet to gain wide clinical application in China owing to their complexity and time-consuming nature. This study aimed to develop the Computerized Neurocognitive Battery for Chinese-Speaking participants (CNBC), an autorun and autoscoring cognitive assessment tool to provide efficient and accurate cognitive evaluations for Chinese-Speaking individuals. METHODS: The CNBC was developed through collaboration between clinical neurologists and software engineers. Qualified volunteers were recruited to complete CNBC and traditional neurocognitive batteries. The reliability and validity of the CNBC were evaluated by analyzing the correlations between the measurements obtained from the computerized and the paper-based assessment and those between software-based scoring and manual scoring. RESULTS: The CNBC included 4 subtests and an autorun version. Eighty-six volunteers aged 51-82 years with 7-22 years of education were included. Significant correlations (0.256-0.666) were observed between paired measures associated with attention, executive function, and episodic memory from the CNBC and the traditional paper-based neurocognitive batteries. This suggests a strong construct validity of the CNBC in assessing these cognitive domains. Furthermore, the correlation coefficients between manual scoring and system scoring ranged from 0.904-1.0, indicating excellent inter-rater reliability for the CNBC. INTERPRETATION: A novel CNBC equipped with automated testing and scoring features was developed in this study. The preliminary results confirm its strong reliability and validity, indicating its promising potential for clinical utilization.


Asunto(s)
Disfunción Cognitiva , Pruebas Neuropsicológicas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pruebas Neuropsicológicas/normas , Reproducibilidad de los Resultados , China , Anciano de 80 o más Años , Disfunción Cognitiva/diagnóstico , Diagnóstico por Computador/métodos , Función Ejecutiva/fisiología , Atención/fisiología , Pueblos del Este de Asia
2.
Biomed Pharmacother ; 180: 117557, 2024 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-39405896

RESUMEN

Huntington's disease (HD), a monogenic neurodegenerative disorder, stems from a CAG repeat expansion within the mutant huntingtin gene (HTT). This leads to a detrimental gain-of-function of the mutated huntingtin protein (mHTT). As of now, there exist no efficacious therapies to alter the disease progression. In view of the monogenetic mutation nature and an indispensable role of wild-type HTT in healthy neurodevelopment and cellular functions, the developing strategy of allele-selectively deleting/silencing mutant HTT as well as only inactivating mHTT without altering wild-type HTT or wild-type huntingtin protein (wtHTT) comes highly recommended, and may offer a promising treatment option for HD. Here, we reviewed the therapeutic approaches that allele-selective lowering mHTT expression by targeting only mutant HTT DNA, RNA and mHTT along with recent preclinical and clinical outcomes and challenges, in anticipation of some novel ideas to be introduced into HD therapeutic research.

3.
Nat Commun ; 15(1): 8792, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39389988

RESUMEN

Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis (OA). Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts. Notably, we found a strong correlation between UCHL1 expression and osteoclast activity in the subchondral bone during OA progression in both human and murine models. Conditional UCHL1 deletion in osteoclast precursors exacerbated OA progression, while its overexpression, mediated by adeno-associated virus 9, alleviated this process in male mice. Mechanistically, RANKL stimulates UCHL1 expression in osteoclast precursors, subsequently stabilizing CD13, augmenting soluble CD13 (sCD13) release, and triggering an autocrine inhibitory effect on the MAPK pathway, thereby suppressing osteoclast formation. These findings unveil a previously unidentified negative feedback loop, RANKL-UCHL1-sCD13, that modulates osteoclast formation and presents a potential therapeutic target for OA.


Asunto(s)
Progresión de la Enfermedad , Osteoartritis , Osteoclastos , Osteogénesis , Ligando RANK , Ubiquitina Tiolesterasa , Ligando RANK/metabolismo , Ligando RANK/genética , Animales , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/genética , Humanos , Osteoclastos/metabolismo , Masculino , Ratones , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Retroalimentación Fisiológica , Ratones Endogámicos C57BL , Persona de Mediana Edad , Modelos Animales de Enfermedad , Huesos/metabolismo , Huesos/patología , Femenino , Ratones Noqueados , Anciano
4.
Heliyon ; 10(13): e33523, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39091927

RESUMEN

How does government spending on environmental protection benefit people's health? The current paper analyzed 2010 and 2018 data from the China Family Panel Studies (CFPS) database to measure the impact of province-level environmental regulations on the health of local population. The study also applied the Alkire Foster method to develop the multidimensional health poverty (MHP) score, a new index intended to measure the health status of individuals in a holistic manner. Our results indicated that more fiscal spending on environmental regulation could improve health of the local population, especially among low-income population living in the rural areas. Further, the size of health benefit differs by the type of environmental regulation. More specifically, regulations focusing on preventing environmental pollution can achieve more sizable health benefits than remedial ones. Finally, fine inhalable particle (PM2.5) has the largest mediating effect on the relationship between environmental regulation and public health. These results provide several policy implications, which highlight the importance of: scaling up fiscal environmental expenditure and optimizing the structure of environmental expenditure with more emphasis on rural areas where more low-income population are located; shifting from ex-post accountability to ex-ante prevention; and strengthening regional cooperation in environmental protection among local governments, and establishing a cross-regional coordination mechanism.

5.
Genes Dis ; 11(5): 101203, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39022126

RESUMEN

Transcriptional factor Forkhead box M1 (FOXM1) plays an important role in pancreatic ductal adenocarcinoma (PDAC) development and progression. The molecular mechanisms underlying its dysregulation remain unclear. We identified and functionally validated the microRNAs (miRNAs) that critically regulate FOXM1 expression in PDAC. The expression levels of miRNA-23a (miR-23a-3p and -5p) were altered in PDAC cell lines and their effects on FOXM1 signaling and cell proliferation and migration and tumorigenesis were examined in vitro and in vivo using mouse PDAC models. Compared with non-tumor pancreatic tissues, PDAC tissues and cell lines exhibited significantly reduced levels of miR-23a expression. Reduced miR-23a expression and concomitant increase in FOXM1 expression were also observed in acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia, the major premalignant lesions of PDAC. Transgenic expression of miR-23a reduced the expression of FOXM1 and suppressed cell proliferation and migration in PDAC cells, whereas the inhibitors of miR-23a did the opposite. Loss or reduced levels of miR-23a increased the levels of FOXM1 expression, while increased expression of FOXM1 down-regulated miR-23a expression, suggesting that miR-23a and FOXM1 were mutual negative regulators of their expression in PDAC cells. Therefore, the miR-23a/FOXM1 signaling axis is important in PDAC initiation and progression and could serve as an interventional or therapeutic target for patients with early or late stages of PDAC.

6.
Mol Carcinog ; 63(10): 1855-1865, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38888207

RESUMEN

Plakophilin 1 (PKP1) belongs to the desmosome family as an anchoring junction protein in cellular junctions. It localizes at the interface of the cell membrane and cytoplasm. Although PKP1 is a non-transmembrane protein, it may become associated with the cell membrane via transmembrane proteins such as desmocollins and desmogleins. Homozygous deletion of PKP1 results in ectodermal dysplasia-skin fragility syndrome (EDSF) and complete knockout of PKP1 in mice produces comparable symptoms to EDSF in humans, although mice do not survive more than 24 h. PKP1 is not limited to expression in desmosomal structures, but is rather widely expressed in cytoplasm and nucleus, where it assumes important cellular functions. This review will summarize distinct roles of PKP1 in the cell membrane, cytoplasm, and nucleus with an overview of relevant studies on its function in diverse types of cancer.


Asunto(s)
Carcinogénesis , Neoplasias , Placofilinas , Humanos , Placofilinas/genética , Placofilinas/metabolismo , Animales , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Citoplasma/metabolismo , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/genética , Desmosomas/metabolismo , Desmosomas/genética
7.
Pharmacol Res Perspect ; 12(2): e1187, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38546116

RESUMEN

The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine-induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD.


Asunto(s)
Microbioma Gastrointestinal , Lantano , Insuficiencia Renal Crónica , Ratas , Animales , Disbiosis , Riñón/metabolismo , Insuficiencia Renal Crónica/metabolismo , Adenina
8.
Chem Biol Drug Des ; 103(1): e14407, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38040413

RESUMEN

Bruceine D (BD) from Brucea javanica (L) exerts an antitumor effect in several human cancers. At present, it has not been reported whether BD inhibits the malignancy of colorectal cancer (CRC) cells. Therefore, investigating the role and regulatory mechanisms of BD in CRC is the main thrust of this study. Effect of BD on CRC cell viability, proliferation, apoptosis, invasion, and autophagy was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell invasion, and western blotting assays. Expression changes of has_circ_0068464 (circ_0068464) were detected using real time quantitative polymerase chain reaction. The molecular mechanisms related to circ_0068464 were predicted through online prediction websites Starbase 2.0, circinteractome, and CircBank and validated using dual-luciferase reporter and RNA pull-down assays. The tumorigenic ability of BD and circ_0068464 on CRC was confirmed by xenograft experiments. The results showed that BD lessened CRC cell proliferation, invasion, autophagy, and prompted cell apoptosis. Circ_0068464 was overexpressed in CRC samples and cells. BD led to a significant reduction in circ_0068464 levels in cells of this carcinoma, but circ_0068464 overexpression partially rescued these effects urged by BD. Also, the combination of BD and circ_0068464 silencing decreased xenograft tumor growth compared to BD alone. Importantly, circ_0068464 could regulate ATG5 expression by functioning as a miR-520h molecular sponge. In conclusion, BD might suppress CRC growth by inhibiting the circ_0068464/miR-520h/ATG5 axis, providing a new perspective for the molecular pathogenesis of CRC and preliminarily indicating that BD may be a promising drug for CRC treatment.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Estricnina/análogos & derivados , Humanos , Carcinogénesis/genética , Autofagia , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , MicroARNs/genética
9.
Crit Rev Anal Chem ; : 1-23, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38039145

RESUMEN

Saliva is one of the most critical human body fluids that can reflect the state of the human body. The detection of saliva is of great significance for disease diagnosis and health monitoring. Microfluidics, characterized by microscale size and high integration, is an ideal platform for the development of rapid and low-cost disease diagnostic techniques and devices. Microfluidic-based saliva testing methods have aroused considerable interest due to the increasing need for noninvasive testing and frequent or long-term testing. This review briefly described the significance of saliva analysis and generally classified the targets in saliva detection into pathogenic microorganisms, inorganic substances, and organic substances. By using this classification as a benchmark, the state-of-the-art research results on microfluidic detection of various substances in saliva were summarized. This work also put forward the challenges and future development directions of microfluidic detection methods for saliva.

10.
Pharmaceutics ; 15(12)2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38140070

RESUMEN

Cancer is a serious disease with an abnormal proliferation of organ tissues; it is characterized by malignant infiltration and growth that affects human life. Traditional cancer therapies such as resection, radiotherapy and chemotherapy have a low cure rate and often cause irreversible damage to the body. In recent years, since the traditional treatment of cancer is still very far from perfect, researchers have begun to focus on non-invasive near-infrared (NIR)-responsive natural macromolecular hydrogel assembly drugs (NIR-NMHADs). Due to their unique biocompatibility and extremely high drug encapsulation, coupling with the spatiotemporal controllability of NIR, synergistic photothermal therapy (PTT), photothermal therapy (PDT), chemotherapy (CT) and immunotherapy (IT) has created excellent effects and good prospects for cancer treatment. In addition, some emerging bioengineering technologies can also improve the effectiveness of drug delivery systems. This review will discuss the properties of NIR light, the NIR-functional hydrogels commonly used in current research, the cancer therapy corresponding to the materials encapsulated in them and the bioengineering technology that can assist drug delivery systems. The review provides a constructive reference for the optimization of NIR-NMHAD experimental ideas and its application to human body.

11.
Curr Vasc Pharmacol ; 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37961858

RESUMEN

OBJECTIVE: To investigate the pharmacological effects and molecular mechanisms of lanthanum hydroxide(LH) on ectopic mineralization of soft tissue and abnormal bone in rats with acute kidney injury(AKI). METHODS: Wistar rats were modeled by 5/6 nephrectomy. After the operation, the rats were divided into different groups, the biochemical indexes of serum collected at different times. Lanthanum hydroxide was administered by intragastric tube at doses of 0.4, 0.2, and 0.1g/kg, respectively. Rats were sacrificed in the 16th week after LH treatment. Observation of pathological changes in tissues were made by specific staining. Western Blot, Real-Time Quantitative PCR, and immunohistochemistry techniques were used to detect the impact on pathway-related proteins. RESULTS: Compared with the control group (no LH administered), the serum phosphate level of the LH group was significantly reduced (P<0.01), calcification of the thoracic aorta was reduced (P<0.05, P<0.01) (Serum biochemical tests before dosing and during drug treatment cycles), renal fibrosis was improved (P<0.01), nuclear entry of nuclear factor kappa-B (NF-κB) was reduced (P<0.01), and the expression of the smooth muscle protein 22α (SM22α) was significantly increased (P<0.01). The expression of osteogenic marker genes was decreased. In addition, compared with the controls, the receptor activator for nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio of the femur in the model group was increased (P<0.05). CONCLUSION: LH can inhibit the occurrence and development of vascular calcification and bone abnormalities in AKI rats by inhibiting the NF-κB and RANKL/OPG signaling pathways.

12.
J Alzheimers Dis ; 96(4): 1489-1504, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38007654

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is a fatal and debilitating neurodegenerative disease. Sphingosine-1-phosphate receptor 2 (S1PR2), one of the receptors of S1P, is a key regulatory factor for various diseases. OBJECTIVE: This study aimed to explore the role and possible mechanism of S1PR2 in AD. METHODS: S1PR2 expression in the AD mice was detected, and after intervening S1PR2 expression with sh-S1PR2 in AD mice, the behavioral changes, pathological lesions of the hippocampus, autophagy level, and AKT/mTOR pathway activation were analyzed. Furthermore, SH-SY5Y cells were induced by Aß25-35 to construct an AD cell model, and the effects of sh-S1PR2 on proliferation, apoptosis, autophagy, and AKT/mTOR pathway of AD cells were investigated. In addition, the effects of pathway inhibitor rapamycin on model cells were further analyzed. RESULTS: The expression of S1PR2 was significantly increased in AD mice, the sh-S1PR2 significantly improved behavioral dysfunction, alleviated pathological injury of the hippocampus, increased the number of neurons, and inhibited Aß production and p-tau expression, showing a positive effect on the AD pathology. In addition, silencing of S1PR2 expression significantly promoted the autophagy level and inhibited the activation of the AKT/mTOR pathway in AD model mice. In vitro experiments further confirmed that sh-S1PR2 promoted cell proliferation, inhibited apoptosis, relieved cytopathology, promoted autophagy, and inhibited the activation of the AKT/mTOR pathway in the cell model. The use of rapamycin further confirmed the role of AKT/mTOR pathway-mediated autophagy in the regulation of AD by S1PR2. CONCLUSION: S1PR2 promoted AD pathogenesis by inhibiting autophagy through the activation of AKT/mTOR pathway.


Asunto(s)
Enfermedad de Alzheimer , Neuroblastoma , Enfermedades Neurodegenerativas , Animales , Humanos , Ratones , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Autofagia , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Sirolimus/farmacología , Receptores de Esfingosina-1-Fosfato , Serina-Treonina Quinasas TOR/metabolismo
13.
Clin Cancer Res ; 29(24): 5183-5195, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37819952

RESUMEN

PURPOSE: Stromal fibrosis limits nutritional supply and disarrays metabolism in pancreatic cancer (PDA, pancreatic ductal adenocarcinoma). Understanding of the molecular basis underlying metabolic cues would improve PDA management. The current study determined the interaction between glucose-regulated proteins 78 (GRP78) and hypoxia-inducible factor 1α (HIF-1α) and its mechanistic roles underlying PDA response to oxygen and glucose restrains. EXPERIMENTAL DESIGN: Gene expression and its association with clinicopathologic characteristics of patients with PDA and mouse models were analyzed using IHC. Protein expression and their regulation were measured by Western blot and immunoprecipitation analyses. Protein interactions were determined using gain- and loss-of-function assays and molecular methods, including chromatin immunoprecipitation, co-immunoprecipitation, and dual luciferase reporter. RESULTS: There was concomitant overexpression of both GRP78 and HIF-1α in human and mouse PDA tissues and cells. Glucose deprivation increased the expression of GRP78 and HIF-1α, particularly colocalization in nucleus. Induction of HIF-1α expression by glucose deprivation in PDA cells depended on the expression of and its own interaction with GRP78. Mechanistically, increased expression of both HIF-1α and LDHA under glucose deprivation was caused by the direct binding of GRP78 and HIF-1α protein complexes to the promoters of HIF-1α and LDHA genes and transactivation of their transcriptional activity. CONCLUSIONS: Protein complex of GRP78 and HIF-1α directly binds to HIF-1α own promoter and LDHA promoter, enhances the transcription of both HIF-1α and LDHA, whereas glucose deprivation increases GRP78 expression and further enhances HIF-1α and LDHA transcription. Therefore, crosstalk and integration of hypoxia- and hypoglycemia-responsive signaling critically impact PDA metabolic reprogramming and therapeutic resistance.


Asunto(s)
Carcinoma Ductal Pancreático , Chaperón BiP del Retículo Endoplásmico , Neoplasias Pancreáticas , Animales , Humanos , Ratones , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Resistencia a Antineoplásicos/genética , Chaperón BiP del Retículo Endoplásmico/metabolismo , Glucosa , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Reprogramación Metabólica/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo
14.
iScience ; 26(9): 107672, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37680460

RESUMEN

Non-natural nucleobase isocytosine (IC) is the isomer of cytosine; its chemical derivate 5-fluoroisocytosine (5-FIC) together with the isocytosine-specific deaminase (ICD) VCZ was suggested to be potential practical enzyme/prodrug pair for cancer therapy through gene-directed enzyme-prodrug therapy (GDEPT) method. In this study, we have determined the crystal structures of apo-VCZ and its complex with 5-FU. We identified the critical residues for substrate binding and catalytic reaction. We also captured the substrate-induced conformational changes of VCZ, then proposed the conjectural reaction procedures of VCZ for converting the IC into the uracil. Moreover, we evaluated the therapeutic effect of wildtype or the mutated VCZ protein in the colorectal cancer cell lines. Our studies will shed light on optimizing the ICD/5-FIC pairs by modifying either the enzyme or the prodrug based on the structural observations, thereby improving the possibility of applying the ICD/5-FIC pair in clinical trials.

15.
Front Endocrinol (Lausanne) ; 14: 1255889, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37745724

RESUMEN

Background: Senescence have emerged as potential factors of lung cancer risk based on findings from many studies. However, the underlying pathogenesis of lung cancer caused by senescence is not clear. In this study, we try to explain the potential pathogenesis between senescence and lung cancer through proteomics and metabonomics. And try to find new potential therapeutic targets in lung cancer patients through network mendelian randomization (MR). Methods: The genome-wide association data of this study was mainly obtained from a meta-analysis and the Transdisciplinary Research in Cancer of the Lung Consortium (TRICL), respectively.And in this study, we mainly used genetic complementarity methods to explore the susceptibility of aging to lung cancer. Additionally, a mediation analysis was performed to explore the potential mediating role of proteomics and metabonomics, using a network MR design. Results: GNOVA analysis revealed a shared genetic structure between HannumAge and lung cancer with a significant genetic correlation estimated at 0.141 and 0.135, respectively. MR analysis showed a relationship between HannumAge and lung cancer, regardless of smoking status. Furthermore, genetically predicted HannumAge was consistently associated with the proteins C-type lectin domain family 4 member D (CLEC4D) and Retinoic acid receptor responder protein 1 (RARR-1), indicating their potential role as mediators in the causal pathway. Conclusion: HannumAge acceleration may increase the risk of lung cancer, some of which may be mediated by CLEC4D and RARR-1, suggestion that CLEC4D and RARR-1 may serve as potential drug targets for the treatment of lung cancer.


Asunto(s)
Estudio de Asociación del Genoma Completo , Neoplasias Pulmonares , Humanos , Estudio de Asociación del Genoma Completo/métodos , Proteómica , Neoplasias Pulmonares/genética , Riesgo , Análisis de la Aleatorización Mendeliana/métodos
16.
J Ovarian Res ; 16(1): 193, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37723573

RESUMEN

BACKGROUND: Evaluating the efficacy of letrozole overlapped with gonadotropin-modified letrozole protocol (mLP) for diminished ovarian reserve (DOR) or advanced-age women with repeated cycles. METHODS: This is a retrospectively registered, paired-match study including 243 women with DOR and 249 women aged over 40 years old who received in vitro fertilization (IVF) treatment. 123 women received stimulation with mLP (mLP group). GnRH agonist (GnRH-a) long, GnRH antagonist (GnRH-anta), and mild stimulation protocol were used as controls with 123 women in each group. We further analyzed 50 of 123 patients in the mLP group who have experienced more than one failed cycles with other ovarian stimulation protocols (non-mLP group). Clinical pregnancy rate (CPR), cumulative clinical pregnancy rate (CCPR), and live birth rate (LBR) were main outcomes. RESULTS: The CPR in the mLP group (38.46%) was significantly higher than mild stimulation (17.11%), but not significantly different from GnRH-a long (26.13%) and GnRH-anta (29.17%) group. The CCPR showed an increasing trend in the mLP group (33.33%) although without significance when compared with controls. The CCRP of GnRH-a long, GnRH-anta, mild stimulation group were 21.68%, 29.03%, and 13.04%, respectively. In women with repeated cycles, mLP achieved the higher available embryo rate (P < 0.05), the top-quality embryo rate, the CPR (P < 0.001), and the LBR (P < 0.001). Further study showed a positive correlation between testosterone and the number of oocytes retrieved in the mLP group (r = 0.395, P < 0.01). CONCLUSION: The mLP may be effective for aged or DOR women who have experienced previous cycle failure by improving the quality of embryos, the CPR, and the LBR. An increasing serum testosterone level may reflect follicular growth during ovarian stimulation.


Asunto(s)
Gonadotropinas , Enfermedades del Ovario , Embarazo , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Letrozol/farmacología , Letrozol/uso terapéutico , Antagonistas de Hormonas , Fertilización In Vitro , Testosterona , Hormona Liberadora de Gonadotropina
17.
Cell Death Dis ; 14(8): 528, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37591827

RESUMEN

Tumor is a representative of cell immortalization, while senescence irreversibly arrests cell proliferation. Although tumorigenesis and senescence seem contrary to each other, they have similar mechanisms in many aspects. Pancreatic ductal adenocarcinoma (PDA) is highly lethal disease, which occurs and progresses through a multi-step process. Senescence is prevalent in pancreatic premalignancy, as manifested by decreased cell proliferation and increased clearance of pre-malignant cells by immune system. However, the senescent microenvironment cooperates with multiple factors and significantly contributes to tumorigenesis. Evidently, PDA progression requires to evade the effects of cellular senescence. This review will focus on dual roles that senescence plays in PDA development and progression, the signaling effectors that critically regulate senescence in PDA, the identification and reactivation of molecular targets that control senescence program for the treatment of PDA.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Páncreas , Neoplasias Pancreáticas/genética , Carcinogénesis/genética , Transformación Celular Neoplásica/genética , Carcinoma Ductal Pancreático/genética , Microambiente Tumoral , Neoplasias Pancreáticas
18.
PLoS One ; 18(8): e0290301, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37603567

RESUMEN

As a natural ecological fragile region, the vast desert steppe in the Inner Mongolia has a developed animal husbandry, and thus posed great impacts on soil quality. In order to accurately evaluate the current situation of soil quality in the desert steppe, it is therefore imperative to adopt a suitable method to effectively assess the soil quality in the region. In this study, the minimum data set (MDS) was established with the help of principal component analysis, Norm value calculation, and correlation analysis, and four indicators, including organic matter, sand grains, soil erosion degree, and pH, were established to evaluate the soil quality of the desert steppe in the Siziwang Banner, a county in the Inner Mongolia. The results from the minimum data set (MDS) method were validated based on the total data set (TDS) method, and the validation indicated that the MDS method can be representative of the soil quality of the study area. The results indicated: 1) the soil quality index (SQI) of 0-30 cm in more than 90% of the study area falls in the range of 0.4 and 0.6 (medium level), while the better level (SQI ≥0.6) only accounted less than 10% of the study area; 2) For the MDS indexes, soil organic matter content at all depths decreased in the southern mountains, central hills, and northern plateau, which is consistent with the changing trends of SQI; 3) The sand grain was the dominant particle in the study region, which was in accordance with the intense wind erosion; 4) The negative correlation was found between the soil pH value and SQI (the high value in pH corresponded to the low value in SQI), which reflected that soil pH has a more stressful effect on the local vegetation. Overall, the MDS indexes in this study can objectively and practically reflect the soil quality in the study area, which can provide a cost effective method for SQI assessment in the desert steppe, which is important for the further grassland ecological construction and grassland management to improve the soil quality in the desert steppes.


Asunto(s)
Arena , Suelo , Animales , Erosión del Suelo , Crianza de Animales Domésticos , China
19.
Int Immunopharmacol ; 120: 110290, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37216800

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is a common neurodegenerative disease and a momentous cause of dementia in the elderly. Sennoside A (SA) is an anthraquinone compound and possesses decisive protective functions in various human diseases. The purpose of this research was to elucidate the protective effect of SA against AD and investigate its mechanism. METHODS: Male APPswe/PS1dE9 (APP/PS1) transgenic mice with a C57BL/6J background were chosen as AD model. Age-matched nontransgenic littermates (C57BL/6 mice) were negative controls. SA's functions in AD in vivo were estimated by cognitive function analysis, Western blot, hematoxylin-eosin staining, TUNEL staining, Nissl staining, detection of Fe2+ levels, glutathione and malondialdehyde contents, and quantitative real-time PCR. Also, SA's functions in AD in LPS-induced BV2 cells were examined using Cell Counting Kit-8 assay, flow cytometry, quantitative real-time PCR, Western blot, enzyme-linked immunosorbent assay, and analysis of reactive oxygen species levels. Meanwhile, SA's mechanisms in AD were assessed by several molecular experiments. RESULTS: Functionally, SA mitigated cognitive function, hippocampal neuronal apoptosis, ferroptosis, oxidative stress, and inflammation in AD mice. Furthermore, SA reduced BV2 cell apoptosis, ferroptosis, oxidative stress, and inflammation induced by LPS. Rescue assay revealed that SA abolished the high expressions of TRAF6 and p-P65 (NF-κB pathway-related proteins) induced by AD, and this impact was reversed after TRAF6 overexpression. Conversely, this impact was further enhanced after TRAF6 knockdown. CONCLUSIONS: SA relieved ferroptosis, inflammation and cognitive impairment in aging mice with AD through decreasing TRAF6.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Ferroptosis , Enfermedades Neurodegenerativas , Anciano , Animales , Humanos , Masculino , Ratones , Envejecimiento , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Inflamación , Lipopolisacáridos , Ratones Endogámicos C57BL , Ratones Transgénicos , Senósidos , Factor 6 Asociado a Receptor de TNF/metabolismo
20.
Heliyon ; 9(4): e15291, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37095918

RESUMEN

Stress can trigger cardiovascular disease. Both imbalance of autonomic nervous activity and increase of neurohormonal output are core aspects of stress responses and can lead to cardiovascular disease. PC6 as a very important acupoint is used to prevent and treat cardiovascular disease and to improve stress-related activities. We examined the influence of electroacupuncture (EA) at PC6 on stress-induced imbalance of autonomic nervous activity and increase of neurohormonal output. EA at PC6 relieved increased cardiac sympathetic nervous activity and decreased cardiac vagal nervous activity induced by immobilization stress. Also, EA at PC6 reduced immobilization stress-induced increases of plasma norepinephrine (NE) and adrenaline (E) released from sympatho-adrenal-medullary axis. Finally, EA at PC6 reduced immobilization stress-induced increases of corticotropin-releasing hormone (CRH) in paraventricular hypothalamic nucleus and plasma cortisol (CORT) released from hypothalamic-pituitary-adrenal axis. However, EA at tail had no significant effect on the stress-induced autonomic and neuroendocrine responses. The results demonstrate the role of EA at PC6 regulating the autonomic and neuroendocrine responses induced by stress and provide insight into the prevention and treatment of EA at PC6 for stress-induced cardiovascular disease by targeting autonomic and neuroendocrine systems.

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