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1.
FEBS J ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567754

ABSTRACT

Acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (IRI) has a high morbidity and mortality, representing a worldwide problem. The kidney is an essential organ of metabolism that has high blood perfusion and is the second most mitochondria-rich organ after the heart because of the high ATP demands of its essential functions of nutrient reabsorption, acid-base and electrolyte balance, and hemodynamics. Thus, these energy-intensive cells are particularly vulnerable to mitochondrial dysfunction. As the bulk of glomerular ultrafiltrate reabsorption by proximal tubules occurs via active transport, the mitochondria of proximal tubules must be equipped for detecting and responding to fluctuations in energy availability to guarantee efficient basal metabolism. Any insults to mitochondrial quality control mechanisms may lead to biological disruption, blocking the clearance of damaged mitochondria and resulting in morphological change and tissue dysfunction. Extensive research has shown that mitochondria have pivotal roles in acute kidney disease, so in this article, we discuss the role of mitochondria, their dynamics and mitophagy in renal ischemia-reperfusion injury.

2.
Phys Rev Lett ; 132(8): 086503, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38457723

ABSTRACT

The use of finite entanglement scaling with matrix product states (MPS) has become a crucial tool for studying one-dimensional critical lattice theories, especially those with emergent conformal symmetry. We argue that finite entanglement introduces a relevant deformation in the critical theory. As a result, the bipartite entanglement Hamiltonian defined from the MPS can be understood as a boundary conformal field theory with a physical and an entanglement boundary. We are able to exploit the symmetry properties of the MPS to engineer the physical conformal boundary condition. The entanglement boundary, on the other hand, is related to the concrete lattice model and remains invariant under this relevant perturbation. Using critical lattice models described by the Ising, Potts, and free compact boson conformal field theories, we illustrate the influence of the symmetry and the relevant deformation on the conformal boundaries in the entanglement spectrum.

3.
Sci Rep ; 13(1): 21175, 2023 12 01.
Article in English | MEDLINE | ID: mdl-38040819

ABSTRACT

Circular RNAs (circRNAs) are linked to cancer, but it's still not clear what role they play in prostatic cancer. Through high-throughput sequencing, the goal of this study was to compare how circRNAs are expressed at different stages of prostate cancer. 12 patients attending the Department of Urology at the Second Affiliated Hospital of Nanchang University between June 2020 and October 2021 were used for RNA sequencing, and 14 patients were used for real-time fluorescent quantitative PCR (qRT-PCR). The expression profiles of prostate cancer circRNAs were constructed by sequencing with the help of next-generation high-throughput sequencing technology, and the differentially expressed circRNAs were analyzed by targeting microRNA (miRNA) loci and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the genes from which circRNAs originated. Finally, the expression of target circRNAs in two prostate tissues was verified by qRT-PCR. Following high-throughput sequencing, 13,047 circRNAs were identified, and 605 circRNAs with significant differential expression were identified, of which 361 circRNAs were up-regulated, and 244 circRNAs were down-regulated. Analysis of circRNA-originated genes using GO and the KEGG enrichment analysis showed that circRNA host genes can regulate and influence multiple signaling pathways in prostate cancer with important biological functions. And the circRNA-miRNA network was constructed. The highest number of differentially expressed circRNA-binding miRNAs were: hsa_circ_000 7582 (52), hsa_circ_000 6198 (37), hsa_circ_000 6759 (28), hsa_circ_000 5675 (25), and hsa_circ_000 2172 (22). Moreover, we further screened out the circRNA (hsa_circ_0005692) that was significantly differentially expressed and common to all groups and verified by qRT-PCR that the expression of the target circRNA (hsa_circ_0005692) was significantly downregulated in prostate cancer compared with benign prostatic hyperplasia (BPH) tissues.


Subject(s)
MicroRNAs , Prostatic Neoplasms , Male , Humans , RNA, Circular/genetics , MicroRNAs/genetics , Base Sequence , Prostatic Neoplasms/genetics , Sequence Analysis, RNA
4.
MedComm (2020) ; 4(6): e464, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38107057

ABSTRACT

Signal transducer and activator of transcription 4 (STAT4) is a critical transcription factor for T helper cell differentiation and tumor cells. Although its prognostic role and gene function have been reported in several carcinomas, the role of STAT4 in vitro and in vivo in breast cancer remains poorly understood. The effect of STAT4 in immunotherapy is also unclear. Therefore, we integrated bulk transcriptomics, experiments, and single-cell transcriptomics to systematically analyze its function in prognosis and signaling pathway. Several clinical breast cancer cohorts confirmed STAT4 as a T-cell relevant prognostic biomarker. Overexpressed STAT4 increased programmed cell death ligand 1 (PD-L1) and major histocompatibility complex class II levels in breast cancer cells. In molecular mechanism, transcriptional synergy between STAT4 and STAT3 transactivated interleukin (IL)-12R and involved a positive feedback loop: STAT4/IL-12R/JAK2-STAT3-STAT4, which contributed to the upregulation of PD-L1 expression. The above signaling axis was defined as the STAT4-related pathway and its score was used to predict T-cell expansion and anti-PD1 treatment response. These findings highlight a novel molecular mechanism indirectly regulating PD-L1 through the STAT4-related pathway: IL-12R/JAK2-STAT3-STAT4/PD-L1, and it has potential application in predicting anti-PD-1 immunotherapy response, which may pave the way for stratified immunotherapy in breast cancer.

5.
Biomed Pharmacother ; 167: 115541, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37738795

ABSTRACT

Toosendanin (TSN), extracted from Melia. toosendan Sieb.et Zucc. and Melia. azedarach L., has been developed into an ascaris repellent in China. However, with the improvement of public health protection, the incidence of ascariasis has been reduced considerably, resulting in limited medical application of TSN. Therefore, it is questionable whether this old ascaris repellent can develop into a drug candidate. Modern studies have shown that TSN has strong pharmacological activities, including anti-tumor, anti-botulinum, anti-viral and anti-parasitic potentials. It also can regulate fat formation and improve inflammation. These researches indicate that TSN has great potential to be developed into a corresponding medical product. In order to better development and application of TSN, the availability, pharmacodynamics, pharmacokinetics and toxicology of TSN are summarized systematically. In addition, this review discusses shortcomings in the current researches and provides useful suggestions about how TSN developed into a drug candidate. Therefore, this paper illustrates the possibility of developing TSN as a medical product, aimed to provide directions for the clinical application and further research of TSN.


Subject(s)
Drugs, Chinese Herbal , Neoplasms , Animals , Humans , Ascaris , Drugs, Chinese Herbal/pharmacology , Neoplasms/drug therapy , China
6.
J Gynecol Obstet Hum Reprod ; 52(7): 102617, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37308039

ABSTRACT

OBJECTIVES: To investigate the characteristics of cervical elastosonography in pregnancies and establish an ultrasound-based combing predictor for improving the prediction in pregnant women with prior-preterm birth who might ultimately undergo preterm birth (PTB). MATERIALS AND METHODS: 169 singleton pregnancies with prior-preterm birth were examined by cervical elastography from January to November of 2021. According to the ultrasound image and result of the following-up, the patients were separated into preterm groups and full-term groups with or without cerclage. There were five elastographic parameters: Elasticity Contrast Index (ECI), Cervical hard tissue Elasticity Ratio (CHR), External Cervical os Strain rate (ES), Closed Internal Cervical os Strain rate (CIS), CIS/ES ratio and CLmin. Multivariable logistic regression was used to screen out the most significant predictors. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the ability of prediction. RESULTS: The PTB group without cerclage showed significantly softer cervix stiffness, while those with cerclage showed significantly harder. CHRmin with P < 0.05 in the univariate logistic regression analysis was screened as a more valuable cervical elastosonography parameter than other ones. The combination of CLmin and CHRmin in un-cerclage and integrating CHRmin, maternal age and pre-pregnancy BMI in cerclage presented good predictive value. The results of AUC were higher than CLmin, respectively (0.775 vs 0.734, 0.729 vs 0.548). CONCLUSIONS: The addition of cervical elastography parameters (such as CHRmin) might improve the ability to predict preterm birth in pregnant women with previous preterm delivery, which was better than using CL alone.


Subject(s)
Cervix Uteri , Premature Birth , Pregnancy , Female , Humans , Infant, Newborn , Cervix Uteri/diagnostic imaging , Pregnant Women , Prospective Studies , Pregnancy Trimester, Second
7.
Am J Transl Res ; 15(5): 3433-3441, 2023.
Article in English | MEDLINE | ID: mdl-37303639

ABSTRACT

OBJECTIVE: This study aimed to explore the efficacy and safety of qi-invigorating blood-activating tongmai decoction combined with rosuvastatin in the treatment of senile type 2 diabetes mellitus (T2DM) complicated with atherosclerosis (AS). METHODS: The clinical data of 122 elderly patients with T2DM complicated with AS treated in Hospital of Chengdu University of Traditional Chinese Medicine from February 2020 to November 2021 were retrospectively analyzed. Among them, 57 patients treated with rosuvastatin alone were divided into a Monotherapy group, and 65 patients treated with qi-invigorating blood-activating tongmai decoction adjuvant combined with rosuvastatin were divided into a combined group. The two groups were compared in terms of efficacy after treatment, incidence of adverse reactions after 8 weeks of treatment, and carotid plaque indexes, glucose metabolism indexes and lipid metabolism indexes before and after 8 weeks of treatment. RESULTS: The Combined group showed a notably higher response rate than the Monotherapy group (P<0.05), but the two groups showed no significant difference in the incidence of adverse reactions (P>0.05). After 8 weeks of treatment, the intima-media thickness (IMT), plaque area, fasting blood glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triacylglycerol (TG) and low-density lipoprotein-cholesterol (LDL-C) in the two groups decreased significantly, and high-density lipoprotein-cholesterol (HDL-C) in them increased significantly. Furthermore, the Combined group showed significantly higher levels of IMT, plaque area, fasting blood glucose, HbA1c, TC, TG and LDL-C, and a significantly lower HDL-C level than the Monotherapy group (P<0.05). CONCLUSION: Qi-invigorating blood-activating tongmai decoction can promote the therapeutic efficacy of rosuvastatin in elderly patients with T2DM complicated with AS.

8.
Arch Gynecol Obstet ; 2023 Jun 27.
Article in English | MEDLINE | ID: mdl-37368143

ABSTRACT

OBJECTIVE: This study set out to investigate a novel ultrasound parameter using cervical elastosonography for improving the prediction of spontaneous preterm birth (sPTB) in twin pregnancies. STUDY DESIGN: The study was comprised of 106 twin pregnancies from October 2020 to January 2022 in Beijing Obstetrics and Gynecology Hospital. They were divided into two groups according to gestational age (GA) at delivery (delivery < 35 weeks and delivery ≥ 35 weeks). There were five elastographic parameters: Elasticity Contrast Index (ECI), Cervical Hardness Ratio (CHR), Closed Internal cervical ostium Strain rate (CIS); External cervical ostium strain rate (ES), CIS/ES ratio and Cervical Length (CL). All of the clinical and ultrasonic indicators with P < 0.1 were considered candidate indicators via univariate logistic regression. Based on the extracted unified combination of clinical indicators, the combinations of permutation with the candidate ultrasound indicators were performed step by step in multivariable logistic regression. The best ultrasound indicator with the lowest Akaike Information Criterion (AIC) and the highest Areas Under the receiver operating characteristic Curve (AUC) was chosen for establishing the prediction score. RESULTS: Over 30% (36/106) of those who delivered before 35 weeks gestation. There were distinct differences in the clinical characteristics and cervical elastography parameters between the two groups. Seven major clinical variables were identified as a unified clinical indicator. CISmin as the best ultrasound elastography predictor indicated the lowest AIC and the highest AUC and outperformed alternative indicators significantly in the prediction of delivery before 35 weeks of gestation. Unfortunately, CLmin which was commonly used in clinical practice ranked far from all of the cervical elastography parameters and presented the highest AIC and the lowest AUC. A preliminary scoring rule was established and the ability to predict the risk of sPTB in twin pregnancies was improved (Accuracy: 0.896 vs 0.877; AIC: 81.494 vs 91.698; AUC: 0.923 vs 0.906). CONCLUSIONS: The cervical elastosonography predictor such as CISmin might be a more useful indicator applied for enhancing the ability in predicting twin pregnancies preterm birth than CL. Furthermore, there would be more benefits for advancing clinical decision-making in actual clinical practice by using cervical elastosonography in the near future.

9.
Front Immunol ; 14: 1197011, 2023.
Article in English | MEDLINE | ID: mdl-37383233

ABSTRACT

Conventional therapy for kidney renal clear cell carcinoma (KIRC) is unpromising. The tumor microenvironment (TME) is intimately linked to the invasiveness of a variety of tumor forms, including KIRC. The purpose of this research is to establish the prognostic and immune-related significance of dihydrolipoamide branched chain transacylase E2 (DBT) in individuals with KIRC. In this investigation, we discovered that DBT expression was down-regulated in a range of human malignancies, and low DBT expression in KIRC was linked to higher-level clinicopathological characteristics as well as a poor prognosis for KIRC patients. Based on the findings of univariate and multivariate Cox regression analyses, DBT might be employed as an independent prognostic factor in KIRC patients. Furthermore, we developed a nomogram to better investigate DBT's predictive usefulness. To confirm DBT expression, we examined KIRC cell lines using RT-qPCR and Western blotting. We also examined the role of DBT in KIRC using colony formation, CCK-8, EdU, transwell, and wound healing assays. We discovered that plasmid-mediated overexpression of DBT in KIRC cells slowed cell proliferation and decreased migration and invasion. Multiple enrichment analyses revealed that DBT may be involved in processes and pathways related to immunotherapy and drug metabolism. We computed the immune infiltration score and discovered that the immunological score and the ESTIMATE score were both greater in the DBT low expression group. According to the CIBERSORT algorithm, DBT seems to promote anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells while inhibiting regulatory T cells. Finally, in KIRC, DBT expression was found to be highly linked to immunological checkpoints, targeted medicines, and immunotherapeutic agents. Our findings suggest that DBT is a distinct predictive biomarker for KIRC patients, playing a significant role in the TME of KIRC and serving as a reference for the selection of targeted treatment and immunotherapy.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Algorithms , Biological Assay , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/therapy , Immunotherapy , Kidney Neoplasms/genetics , Tumor Microenvironment
10.
Eur J Gastroenterol Hepatol ; 35(1): 80-88, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36165067

ABSTRACT

BACKGROUND: Albumin therapy in patients with decompensated liver cirrhosis has always been a controversial issue. This study aimed to investigate the efficacy and safety of albumin in reducing mortality and controlling complications in patients with liver cirrhosis and provide a reference for relevant decision-making. METHODS: Databases such as PubMed, EMBASE, and Web of Science were searched to collect eligible articles published before January 2022, which were analyzed by Revman 5.3. RESULTS: A total of 10 randomized controlled trials (2040 patients) were included. Based on the meta-analysis results, no significant difference in mortality was shown between the albumin administration group and the control group (HR = 1.01; 95% CI, 0.97-1.05; P = 0.62). Subgroup analysis showed that albumin administration had no significant short-term or long-term survival benefits in patients with decompensated liver cirrhosis and increased the risk of pulmonary edema adverse reactions (RR = 3.14; 95% CI, 1.48-6.65; P = 0.003). Subgroup analysis based on albumin administration time showed that short-term (HR = 0.93; 95% CI, 0.76-1.13; P = 0.47) or long-term (HR = 0.97; 95% CI: 0.87-1.08; P = 0.58) administration of albumin could not significantly reduce the mortality of patients with decompensated liver cirrhosis. In contrast, albumin administration could significantly reduce the recurrence rate of ascites (RR = 0.56; 95% CI, 0.46-0.68; P = 0.000). CONCLUSION: Short-term(<1 month) or long-term (>1 month) administration of albumin can not significantly reduce the mortality of patients with decompensated liver cirrhosis, and a large amount of albumin infusion will increase the risk of pulmonary edema.


Subject(s)
Ascites , Pulmonary Edema , Humans , Ascites/therapy , Pulmonary Edema/complications , Randomized Controlled Trials as Topic , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Albumins/adverse effects
11.
Phys Rev Lett ; 129(21): 210601, 2022 Nov 18.
Article in English | MEDLINE | ID: mdl-36461979

ABSTRACT

Some quantum critical states cannot be smoothly deformed into each other without either crossing some multicritical points or explicitly breaking certain symmetries even if they belong to the same universality class. This brings up the notion of "symmetry-enriched" quantum criticality. While recent works in the literature focused on critical states with robust degenerate edge modes, we propose that the conformal boundary condition (B.C.) is a more generic characteristic of such quantum critical states. We show that in two families of quantum spin chains, which generalize the Ising and the three-state Potts models, the quantum critical point between a symmetry-protected topological phase and a symmetry-breaking order realizes a conformal B.C. distinct from the simple Ising and Potts chains. Furthermore, we argue that the conformal B.C. can be derived from the bulk effective field theory, which realizes a novel bulk-boundary correspondence in symmetry-enriched quantum critical states.

12.
Front Oncol ; 12: 1030626, 2022.
Article in English | MEDLINE | ID: mdl-36387158

ABSTRACT

We reported a case of pure laparoscopic radical nephroureterectomy for complicated renal pelvis carcinoma combined with horseshoe kidney (HSK). The aim was to present a case report and review of the literature about renal pelvis carcinoma combined with HSK. The case report includes a history of patient data. The pure laparoscopic radical nephroureterectomy was provided with the informed consent of the patient. A 53-year-old patient was diagnosed with a right renal pelvis mass with HSK. We performed laparoscopic radical nephroureterectomy with partial cystectomy and horseshoe renal isthmus amputation. Histopathological features, computed tomography urography (CTU), and angiography (CTA) confirmed the diagnosis of renal pelvis carcinoma combined with HSK. The tumor was removed, and the patient had an uneventful recovery. Renal pelvis carcinoma combined with HSK is a rare case. Due to severe anatomical abnormalities, this disease is a major challenge for urologists. We share our successful case for readers to learn from.

13.
Front Surg ; 9: 909854, 2022.
Article in English | MEDLINE | ID: mdl-36338658

ABSTRACT

Objective: Long-chain acyl-coenzyme A synthases (ACSLs) catalyze the activation of fatty acid and are often dysregulated in malignancies. The purpose of this research was to figure out the ACSL3's prognostic value and mechanism in clear cell renal cell carcinoma (ccRCC). Methods: The expression of ACSL3 in ccRCC was investigated in this work using data from the GEO, TCGA, Oncomine and HPA databases. The expression differences of ACSL3 in the cell lines were further detected by qPCR and Western blot. GEPIA, MethSurv, cBioPortal, and the TIMER were used to perform survival and correlation analysis on ACSL3. GO and KEGG analyses were carried out in R using clusterProfiler and GOplot. Protein-protein interactions (PPI) are constructed from Strings website, and the results were visualized in Cytoscape software. Results: The expression level of ACSL3 was significantly reduced in ccRCC tissues, and its mRNA and protein expression were also significantly lower in both renal cancer cell lines. ACSL3 is significantly related to clinical stage, OS, DFS, DNA methylation, and immune-cell infiltration. Conclusion: Our findings demonstrated that data mining was capable of eliciting information on ACSL3 levels and its role in genetic regulatory pathways in ccRCC.

14.
Biomed Res Int ; 2022: 3360316, 2022.
Article in English | MEDLINE | ID: mdl-36277880

ABSTRACT

Objective: To investigate the risk of cardiovascular and neurodegenerative diseases induced by matrix metalloproteinases (MMPs) by meta-analysis. Methods: Relevant literature was searched from Wanfang Medical Center, CNQI, VIP, PubMed, and other domestic and foreign literature databases for the research direction, and the risk of cardiovascular and neurodegenerative diseases induced by MMPs was meta-analyzed using the fixed-effect model and random-effect model. Results: MMP-1 and MMP-9 were risk factors for cardiovascular diseases by fixed and random-effect model analysis, respectively, while MMP-2 and MMP-9 were risk factors for increased neurodegenerative diseases by random-effect model analysis. Conclusion: MMP-1 and MMP-9 are risk factors for cardiovascular diseases, and MMP-2 and MMP-9 are major factors for increased risk of neurodegenerative diseases. MMP-1, MMP-2, and MMP-9 can be used as new targets for clinical diagnosis, treatment, and research of subsequent cardiovascular and neurodegenerative diseases.


Subject(s)
Cardiovascular Diseases , Neurodegenerative Diseases , Humans , Matrix Metalloproteinase 9 , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 1 , Matrix Metalloproteinases
15.
Front Mol Biosci ; 9: 910928, 2022.
Article in English | MEDLINE | ID: mdl-36275614

ABSTRACT

Cuproptosis is a novel kind of programmed cell death that has been linked to tumor development, prognosis, and responsiveness to therapy. Nevertheless, the precise function of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) remains unknown. We characterized the genetic and transcriptional changes of CRGs in papillary renal cell carcinoma (PRCC) samples and analyzed the expression patterns in two separate cohorts. We observed that two unique cuproptosis-related subgroups and three separate gene subgroups were connected with clinicopathological, prognostic, and TME features of patients. Then, a risk score for predicting overall survival (OS) was created and validated in patients with PRCC. To make the risk score more clinically useful, we created a nomogram that was very accurate. A lower risk score, which was associated with higher tumor mutation burden, and immune activity, suggested a better prognosis for OS. Additionally, the risk score was shown to be substantially linked with the drug's susceptibility to chemotherapeutic agents. Our extensive research of CRGs in PRCC identified possible roles for them in the TME, clinicopathological features, and overall survival. These findings may help advance our knowledge of CRGs in PRCC and pave the way for improved prognosis and the creation of more effective immunotherapy therapies.

16.
Oxid Med Cell Longev ; 2022: 7142314, 2022.
Article in English | MEDLINE | ID: mdl-36082081

ABSTRACT

Renal ischemia-reperfusion injury (RIRI) is a common pathological process that causes kidney injury. Previous studies have indicated that both peroxisome proliferator-activated receptor γ (PPARγ) and microRNA-21 (miR-21) exert protective effects against RIRI. However, their relationship is not well understood. In the present study, we investigated the role of the PPARγ/miR-21/programmed cell death 4 (PDCD4) axis in IRI, both in vivo and in vitro. In vitro cell hypoxia/reoxygenation (H/R) and in vivo RIRI models were established, and cell viability, cell apoptosis, and key molecule expression profiles were analyzed. Our results showed that both PPARγ and miR-21 had protective effects against RIRI to varying degrees, and there was an interaction between PPARγ and miR-21. PPARγ could promote the expression of miR-21 and partially protect against RIRI by reducing the level of the miR-21 target protein (PDCD4). Our findings underscore the potential utility of future clinical investigations of PPARγ activation and targeting of the underlying miR-21/PDCD4/caspase-3 pathway, which may participate in the pathogenesis of human IRI.


Subject(s)
MicroRNAs , PPAR gamma , Reperfusion Injury , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Humans , Kidney/pathology , MicroRNAs/metabolism , PPAR gamma/metabolism , RNA-Binding Proteins/metabolism , Reperfusion Injury/pathology , Signal Transduction
17.
Neuropharmacology ; 219: 109253, 2022 11 15.
Article in English | MEDLINE | ID: mdl-36108796

ABSTRACT

High-frequency stimulation (HFS) of the sciatic nerve leads to long-term potentiation (LTP) at C-fiber synapse and long-lasting pain hypersensitivity. The underlying mechanisms, however, are still unclear. In the present study, we investigated the involvement of astrocytes derived l-lactate in the spinal dorsal horn subsequent to glucocorticoid (GC) secretion into the plasma in this process using Sprague-Dawley rats and Aldh1L1-CreERT2 mice of either sex. We found that HFS increased l-lactate and monocarboxylate transporters 1/2 (MCT1/2) in the spinal dorsal horn. Inhibition of glycogenolysis or blocking lactate transport prevented the induction of spinal LTP following HFS. Furthermore, Chemogenetical inhibition of dorsal horn astrocytes, which were activated by HFS, prevented spinal LTP, alleviated the mechanical allodynia and the decreased the level l-lactate and GFAP expression in the dorsal horn following HFS. In contrast, Chemogenetics activation of dorsal horn astrocytes in naïve rats induced spinal LTP as well as mechanical allodynia, and increased GFAP expression and l-lactate. Application of l-lactate directly to the spinal cord of naïve rats induced spinal LTP, mechanical allodynia, and increased spinal expression of p-ERK. Importantly, HFS increased GC in the plasma and glucocorticoid receptor (GR) expression in spinal astrocytes, adrenalectomy or knocking down of GR in astrocytes by using Cre-Loxp system blocked the mechanical allodynia, prevented the spinal LTP and the enhancement of lactate after HFS. These results show that lactate released from spinal astrocytes following glucocorticoid release into the plasma enhance synaptic transmission at the C-fiber synapse and underlie pain chronicity.


Subject(s)
Hyperalgesia , Long-Term Potentiation , Animals , Astrocytes/metabolism , Glucocorticoids/metabolism , Glucocorticoids/pharmacology , Hyperalgesia/metabolism , Lactic Acid/metabolism , Long-Term Potentiation/physiology , Mice , Pain/metabolism , Posterior Horn Cells , Rats , Rats, Sprague-Dawley , Receptors, Glucocorticoid/metabolism , Spinal Cord/physiology , Spinal Cord Dorsal Horn
18.
Front Mol Biosci ; 9: 871602, 2022.
Article in English | MEDLINE | ID: mdl-35402508

ABSTRACT

Background: Immunotherapy has emerged as an important technique for treating a variety of cancers. The dynamic interplay between tumor cells and invading lymphocytes in the tumor microenvironment is responsible for the good response to immunotherapy (TME). Pyroptosis, or inflammation-induced cell death, is closely linked to a number of cancers. However, in papillary renal cell carcinoma (KIRP), the association between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy impact remains unknown. Methods: We carefully investigated the link between pyroptosis and tumor growth, prognosis, and immune cell infiltration by evaluating 52 pyroptosis-related genes. The PRG score was utilized to measure a single tumor patient's pyroptosis pattern. After that, we looked at how well these values predicted prognoses and therapy responses in KIRP. Results: We discovered that PRG differences between subgroups were linked to clinical and pathological aspects, prognosis, and TME in two separate genetic subtypes. After that, a PRG score for estimating overall survival (OS) was developed, and its predictive potential in KIRP patients was confirmed. As a result, we developed a very precise nomogram to improve the PRG score's clinical usefulness. A low PRG score, which is determined by mutation load and immune activation, suggests a good chance of survival. Furthermore, the PRG score was linked to chemotherapeutic drug sensitivity in a substantial way. Conclusions: The possible functions of PRGs in the TME, clinical and pathological characteristics, and prognosis were established in our thorough investigation of PRGs in KIRP. These results might help us better understand PRGs in KIRP and offer a new avenue for prognostic evaluation and the development of more effective immunotherapy treatments.

19.
Cancer Med ; 11(21): 3993-4004, 2022 11.
Article in English | MEDLINE | ID: mdl-35322581

ABSTRACT

Renal cell carcinoma (RCC) seriously threatens people's lives and health. The identification of some precise biomarkers during the process of RCC progression and the pathophysiologic procedure is critical for improving the diagnosis and management of RCC. Evidence suggests that ferroptosis may play a pivotal role in eradicating clear cell RCC (ccRCC, KIRC) tumor cells. We screened out the target prognostic ferroptosis-associated genes and examined the functions of farnesyl-diphosphate farnesyltransferase (FDFT1) in 786-O cells by plasmid transfection. In our study, we identified FDFT1 as a potential marker correlating with ferroptosis in KIRC. Upregulated FDFT1 inhibited cell proliferation, migration, and invasion, and the underlying antitumor effects may occur via the AKT signaling pathway. Our study provides helpful evidence to study the complex physiopathology of KIRC.


Subject(s)
Carcinoma, Renal Cell , Ferroptosis , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Ferroptosis/genetics , Cell Line, Tumor , Biomarkers , Kidney Neoplasms/pathology
20.
J Vis Exp ; (179)2022 01 07.
Article in English | MEDLINE | ID: mdl-35068478

ABSTRACT

The field of moxibustion research is expanding, with a rapid increase in publications in recent years. Moxibustion is a therapy that ignites moxa on the skin of humans, with an increase in peripheral skin temperature and localized redness. During this treatment, the recipient must remain still to prevent scalding and expose intervention sites for easy manipulation; however, maintaining a fixed posture during moxibustion is a big challenge for animals. Thus, manipulating moxibustion in small animals, such as mice, can lead to several difficulties for researchers. In addition, an uncomfortable posture for animals can lead to fear and resistance to moxibustion, increased risk of injury, diminished animal welfare, and less valid research data. An efficient, comfortable moxibustion method is needed to protect animal welfare and minimize the adverse effects on experimental results. However, moxibustion methods are highly variable and often have limited efficacy. More importantly, an uncomfortable moxibustion posture might cause a stress response, such as those observed with anxiety, fear, and anger, which could influence the research data. Therefore, strategies for animal moxibustion that inflict the least harm possible during the intervention are required. This protocol introduces a mouse tethering method for moxibustion intervention, minimizing mouse discomfort and improving study efficiency. Essential strategies for tethering mice and application of moxibustion are highlighted, and the structure of the tethering instrument is described.


Subject(s)
Moxibustion , Acupuncture Points , Animal Welfare , Animals , Mice , Skin , Skin Temperature
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