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In recent years, the application of numerical simulation in the research and development(R&D) as well as the pharmaceutical processes of new drugs has expanded considerably. The discrete element method(DEM), an important approach among numerical simulation methods, offers an effective tool for the simulation of discontinuous media. Referring to the research progress of DEM and the formulation of solid traditional Chinese medicine(TCM) preparations in recent years, this paper summarizes and analyzes the application of DEM in the pharmaceutical processes of solid TCM preparations, and discusses the challenges of its application in these processes, in order to provide new methods and ideas for promoting the high-quality production of TCM preparations.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Química Farmacêutica/métodos , Composição de Medicamentos/métodosRESUMO
Condensed tannins were isolated from the bark of Ficus altissima and fractionated into four subcomponents on a Sephadex LH-20 column with 60 %, 80 %, 100 % methanol, and 70 % acetone, separately. Their structures were characterized by MALDI-TOF MS coupled with HPLC-ESI-MS and confirmed to be polymers of B-type procyanidin glucosides, procyanidins, and prodelphinidin glucosides. The degree of polymerization (DP) of these polymers was as high as 21, and the mDPs of the four subcomponents were calculated as 2.4, 6.6, 10.5 and 13.4, respectively. They competitively or noncompetitively suppressed the activities of tyrosinase and α-glucosidase through hydrogen bonding and hydrophobic interaction. And they also showed a powerful antioxidative activity. Correlation analyses verified that the anti-tyrosinase capacity exhibited a significant positive correlation (R2monophenolase = 0.9167 and R2diphenolase = 0.9302) with mDP within the methanol-water system, and the anti-α-glucosidase activity also showed a significant positive correlation with the mDP (R2 = 0.9187). In contrast, the antioxidant capability showed a significant negative correlation with the mDP (R2DPPH = 0.9258, R2ABTS = 0.9372). This study confirmed that condensed tannins from the bark of F. altissima were desirable anti-tyrosinase, anti-α-glucosidase, and antioxidant agents, and elucidated the relationships of their mDP (molecular weight) and activities, which provided a scientific basis for the comprehensive utilization of these polymers in the food, cosmetics, medicine and other fields.
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Antioxidantes , Ficus , Casca de Planta , Polimerização , Proantocianidinas , Ficus/química , Casca de Planta/química , Antioxidantes/química , Antioxidantes/farmacologia , Proantocianidinas/química , Proantocianidinas/isolamento & purificação , Proantocianidinas/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , alfa-Glucosidases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Taninos/química , Taninos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificaçãoRESUMO
Organ transplantation from donors with immune thrombocytopenia (ITP), a condition involving the autoantibody-mediated destruction of platelets, is a topic of debate due to the potential for transplantation-mediated autoimmune thrombocytopenia (TMAT), a rare but potentially fatal complication. Previous reports have described transplants from deceased liver donors with ITP who had very low platelet counts and disease largely refractory to treatment. Here, we present the first case of living kidney transplantation from a donor with ITP who underwent preoperative treatment, with concurrent splenectomy performed to reduce the long-term risk of spontaneous hemorrhage. To ensure the safety of the procedure, we monitored perioperative rotational thromboelastometry parameters and platelet counts, leading to the normalization of the donor's platelet levels. The recipient experienced an uneventful recovery of renal function without perioperative bleeding or the development of TMAT. Our report suggests that kidney transplantation from a donor with well-managed ITP is safe, and such a condition should not be considered a contraindication for donation.
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BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited. METHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN. RESULTS: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model. CONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.
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Ácidos Aristolóquicos , Nefropatias , Fatores de Transcrição , Ácidos Aristolóquicos/toxicidade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/genética , Animais , Camundongos , Humanos , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Mapas de Interação de ProteínasRESUMO
INTRODUCTION: Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial. METHODS: We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles. RESULTS: Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC-1 and P-selectin when exposed to agonist stimulations. PAC-1 expression increased under high adenosine diphosphate (ADP) stimulation, while P-selectin expression increased under both high ADP and thrombin receptor-activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC-1 and P-selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet-derived microparticles showed a significant increase. CONCLUSION: Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet-derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice.
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Plaquetas , Neoplasias Hematológicas , Transfusão de Plaquetas , Humanos , Transfusão de Plaquetas/métodos , Neoplasias Hematológicas/terapia , Plaquetas/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Testes de Função Plaquetária , Contagem de Plaquetas , Selectina-P/sangue , Micropartículas Derivadas de Células/metabolismoRESUMO
BACKGROUND: In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer. OBJECTIVE: This study aims to evaluate the effectiveness of Chinese herbal medicine (CHM) as a complementary treatment for neutropenia prevention and immunity modulation during chemotherapy in patients with breast cancer. METHODS: We will conduct a real-world pragmatic clinical trial to evaluate the effectiveness of CHM as a supplementary therapy to prevent neutropenia in patients with breast cancer undergoing chemotherapy. Patients will be classified into CHM or non-CHM groups based on whether they received CHM during chemotherapy. Using generalized estimating equations or repeated measures ANOVA, we will assess differences in white blood cell counts, absolute neutrophil counts, immune cells, and programmed cell death protein 1 (PD-1) expression levels between the 2 groups. RESULTS: This study was approved by the research ethics committee of Hualien Tzu Chi Hospital (IRB 110-168-A). The enrollment process began in September 2021 and will stop in December 2024. A total of 140 patients will be recruited. Data cleaning and analysis are expected to finish in the middle of 2025. CONCLUSIONS: Traditional Chinese medicine is the most commonly used complementary medicine, and it has been reported to significantly alleviate chemotherapy-related side effects. This study's findings may contribute to developing effective interventions targeting chemotherapy-related neutropenia among patients with breast cancer in clinical practice. TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry ITMCTR2023000054; https://tinyurl.com/yc353hes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55662.
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Hematopoietic stem cell (HSC) transplantation, using either bone marrow (BM) or peripheral blood stem cells (PBSC), is a well-established therapy for various hematologic and non-hematologic diseases. However, the long-term health outcomes after HSC donation remain a major concern for several potential donors. Thus, we aimed to conduct a matched cohort study of 5003 unrelated donors (1099 BM and 3904 PBSC) and randomly selected 50,030 matched controls based on age, sex, and resident area from the donor registry between 1998 and 2018. The medical insurance claims of all the participants were retrieved from the Taiwan National Health and Welfare Data Science Center after de-identification. Our findings revealed no differences in the incidence of cancer, death, and catastrophic diseases between HSC donors and matched healthy participants during long-term follow-up. Kaplan-Meier curves depicting the cumulative incidence of cancer and overall mortality throughout the follow-up period also demonstrated similar outcomes between donors and non-donors. In conclusion, our results indicate that HSC donation, whether through BM or PBSC, is safe and not associated with an increased risk of cancer, death, or catastrophic diseases. These findings provide valuable information for counseling potential HSC donors and for long-term management of HSC donor health.
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Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Neoplasias/terapia , Masculino , Feminino , Seguimentos , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Pessoa de Meia-Idade , Estudos de Coortes , Doença Catastrófica , Taiwan/epidemiologia , Doadores de TecidosRESUMO
BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.
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Infecções por Citomegalovirus , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Infecções por Citomegalovirus/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Taiwan/epidemiologia , Fatores de Risco , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Incidência , Adulto Jovem , Citomegalovirus/isolamento & purificação , Doença Enxerto-Hospedeiro/epidemiologia , Adolescente , Idoso , Transplante Homólogo/efeitos adversos , Criança , Pré-Escolar , Sistema de RegistrosRESUMO
Background: In recent years, Klebsiella pneumoniae has attracted attention because of its increasing drug resistance. At the same time, the migration and pathogenicity caused by its virulence genes also bring many difficulties to the diagnosis and treatment of clinical infections. However, it is currently unclear whether there are differences in virulence and pathogenicity with changes in drug resistance. Objective: To understand the differences in molecular characteristics and expression of virulence genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-sensitive Klebsiella pneumoniae (CSKP). Methods: Using polymerase chain reaction (PCR), we examined capsule polysaccharide-related genes and virulence genes in 150 clinical isolates of CRKP and 213 isolates of CSKP from the local area in Ningbo, China. Multilocus sequence typing (MLST) was used to analyze the phylogenetic relationships of clinical Klebsiella pneumoniae isolates. Furthermore, real-time quantitative PCR (RT-qPCR) was used to analyze the expression differences of common virulence genes in CSKP and CRKP, and the virulence was further verified by the larval model of Galleria mellonella. Results: The study found that the detection rates of genes rmpA, iroB, peg-344, magA, aerobactin, alls, kfu, and entB were significantly higher in CSKP compared to CRKP. The capsule gene types K1 and K2 were more common in CSKP, while K5 was more common in CRKP. Hypervirulent Klebsiella pneumoniae (hvKP) was predominantly from CSKP. CRKP strains exhibited noticeable homogeneity, with ST11 being the predominant sequence type among the strains. CSKP strains showed greater diversity in ST types, but ST23 was still the predominant sequence type. Carbapenem-sensitive hypervirulent Klebsiella pneumoniae (CS-hvKP) had higher expression of rmpA and rmpA2 genes compared to carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). In the wax moth virulence model, the survival rate of CS-hvKP was significantly lower than that of CR-hvKP. Conclusion: There is a significant difference in the distribution of virulence genes between CSKP and CRKP, with CSKP carrying a significantly greater number of virulence genes. Furthermore, compared to CSKP, CRKP strains exhibit noticeable homogeneity, with ST11 being the predominant sequence type among the strains. Additionally, in terms of virulence gene expression efficiency and virulence, CSKP is significantly higher than CRKP.
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Hemorrhagic shock (HS) leads to intestinal damage and subsequent multiple organ dysfunction syndrome. Intestinal barrier dysfunction is the main cause of multiple organ failure associated with HS. Leukocyte immunoglobulin-like receptor B4 (Lilrb4) belongs to the Ig superfamily and is a vital natural immunomodulatory receptor. The purpose of this study was to identify the role and molecular mechanism of Lilrb4 in HS-induced ileal injury. In this work, HS was established by femoral artery cannula and 90 min of HS (blood pressure, 35-40 mmHg), followed by resuscitation. RNA sequencing analysis showed that Lilrb4 was highly expressed in the ileum of HS rats. As observed, HS rats exhibited severe ileal injury, characterized by enlarged subepithelial space, edema, exfoliation and extensive loss of villi. Whereas, lentivirus system-mediated Lilrb4 overexpression considerably mitigated these alterations. HS led to increased release of markers associated with intestinal injury, which was effectively reversed by Lilrb4 overexpression. In addition, after resuscitation, Lilrb4 overexpression inhibited HS-triggered inflammatory response, as evidenced by decreased levels of proinflammatory cytokines. Lilrb4 also inhibited the activation of NF-κB signal induced by HS. Notably, Lilrb4 modulated the balance of regulatory T (Treg)-T helper 17 (Th17) cells in the mesenteric lymph node (MLN), which may also contribute to its protective role in HS progression. In aggregate, these findings confirmed that Lilrb4 overexpression protected against ileal injury caused by HS, indicating that Lilrb4 may be a potential candidate for the treatment of HS.
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NF-kappa B , Choque Hemorrágico , Animais , Ratos , Íleo/metabolismo , NF-kappa B/metabolismo , Choque Hemorrágico/complicações , Transdução de SinaisRESUMO
OBJECTIVE: To compare the clinical outcomes of transoral anterior Jefferson-fracture reduction plate (JeRP) and posterior screw rod (PSR) surgery for unstable atlas fractures via C1-ring osteosynthesis. METHODS: From June 2009 to June 2022, 49 consecutive patients with unstable atlas fractures were treated by transoral anterior JeRP fixation (JeRP group) or PSR fixation (PSR group) and followed up at General Hospital of Southern Theatre Command of PLA; 30 males and 19 females were included. The visual analogue scale (VAS) score, Neck Disability Index (NDI), distance to anterior arch fracture (DAAF), distance to posterior arch fracture (DPAF), lateral mass displacement (LMD), Redlund-Johnell value, postoperative complications, and fracture healing rate were retrospectively collected and statistically analyzed. RESULTS: Compared with that in the PSR group, the bleeding volume in the JeRP group was lower, and the length of hospital stay was longer. The VAS scores and NDIs of both groups were significantly improved after surgery. The postoperative DAAF and DPAF were significantly smaller after surgery in both groups. Compared with the significantly shorter DPAF in the PSR group, the JeRP group had a smaller DAAF, shorter LMDs and larger Redlund-Johnell value postoperatively and at the final follow-up. The fracture healing rate at 3 months after surgery was significantly greater in the JeRP group (p < 0.05). CONCLUSION: Both C1-ring osteosynthesis procedures for treating unstable atlas fractures yield satisfactory clinical outcomes. Transoral anterior JeRP fixation is more effective than PSR fixation for holistic fracture reduction and short-term fracture healing, but the hospital stay is longer.
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BACKGROUND: Dermoscopy is a noninvasive technique that has attracted increasing attention in the field of inflammatory skin diseases (such as psoriasis) in recent years. OBJECTIVE: This study aimed to provide an up-to-date overview of the role of dermoscopy in the diagnosis and extra-diagnosis of psoriasis. METHODS: This study sought to review the published literature regarding use of dermoscopy in the evaluation of psoriasis. RESULTS: The diagnostic value of dermoscopy in psoriasis vulgaris, nail psoriasis, and other types of psoriasis was summarized from the aspects of vascular pattern, scale pattern, and other features. Meanwhile, the application value of dermoscopy in the differential diagnosis, efficacy and severity assessment, prediction and monitoring of psoriasis was discussed. CONCLUSION: Dermoscopy has good clinical value in the diagnosis and differential diagnosis of psoriasis and shows great prospects for severity assessment and efficacy prediction monitoring.
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Dermatite , Doenças da Unha , Psoríase , Humanos , Dermoscopia/métodos , Psoríase/diagnóstico por imagem , Doenças da Unha/diagnóstico por imagem , Diagnóstico DiferencialRESUMO
The authors wish to make the following corrections to this published paper [...].
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OBJECTIVE: To compare outcomes in women undergoing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery. DESIGN: This retrospective, propensity-score matched cohort study from the New York State cardiac registry (2012-2018) included all women with multivessel coronary artery disease undergoing PCI with everolimus-eluting stents (EES) and CABG surgery. The primary outcome was all-cause mortality. The key secondary outcome was major adverse cardiac events, defined as the composite of all-cause mortality, myocardial infarction, and stroke. RESULTS: PCI with EES was associated with a higher 6-year risk of mortality (25.75% vs 23.57%; adjusted hazard ratio [AHR], 1.29; 95% confidence interval [CI], 1.14-1.45). PCI also was associated with a higher rate of the composite outcome of death, myocardial infarction, and stroke (36.58% vs 32.89%; AHR, 1.28; 95% CI, 1.17-1.41), as well as myocardial infarction (14.94% vs 9.12%; AHR, 1.84; 95% CI, 1.56-2.17), but not stroke (7.07% vs 7.62%; AHR, 0.83; 95% CI, 0.67-1.03). Repeat revascularization rates also were higher for women undergoing PCI (21.53% vs 11.57%; AHR, 1.88; 95% CI, 1.63-2.17). There was no difference in mortality between the 2 interventions when PCI patients received complete revascularization or had noncomplex lesions and for women without diabetes. CONCLUSIONS: For women with multivessel coronary artery disease, CABG surgery is associated with lower 6-year mortality, myocardial infarction, and repeat revascularization rates compared to PCI with EES.
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Acute-phase markers are often used to evaluate the disease activity of rheumatoid arthritis (RA). Occasionally, the serum levels of acute-phase reactants remain normal in patients with obvious inflamed joints. Hematological indices derived from complete blood counts have been shown to correlate with disease activity. This provides a potential practical implementation in daily practice. Only a few studies have evaluated the relation between hematological indices and novel RA treatment (i.e., biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); no research has examined the changes in hematological indices in RA treatments longitudinally. We conducted a retrospective study involving 273 RA patients with b/tsDMARD treatment and followed them for at least a year. Baseline, 3-month, and 6-month lab data were collected. The results indicated a reduction in the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) post-treatment. Higher baseline PLRs and SIIs were associated with a more significant reduction in ESR at three months (η2 = 0.03/0.13, p = 0.21/0.023). NLR and SII correlated with CRP moderately at three months (r = 0.373/0.394, p < 0.001/< 0.001). A correlation comparison showed that the correlation of NLR and PLR with CRP differs during different periods (p = 0.037/0.004). Subgroup analysis revealed that the time effect on correlation is related to treatment with Janus kinase inhibitor and anti-interleukin-6 but not antitumor necrosis factors.
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Pyroptosis is a new form of programmed cell death recognized as crucial in developing sepsis. However, there is limited research on the mechanism of pyroptosis-related genes in sepsis-related from the Gene Expression Omnibus (GEO) database and standardized. The expression levels of pyroptosis-related genes were extracted, and differential expression analysis was conducted. A prediction model was constructed using random forest (RF), support vector machine (SVM), weighted gene co-expression new analysis (WGCNA), and nomogram techniques to assess the risk of sepsis. The relationship between pyroptosis-related subgroups and the immune microenvironment and inflammatory factors was studied using consistent clustering algorithms, principal component analysis (PCA), single-sample genomic enrichment analysis (ssGSEA), and immune infiltration. A risk prediction model based on 3 PRGs has been constructed and can effectively predict the risk of sepsis. Patients with sepsis can be divided into two completely different subtypes of pyroptosis-related clusters. Cluster B is highly correlated with the lower proportion of Th17 celld and has lower levels of expression of inflammatory factors. This study utilizes mechanical learning methods to further investigate the pathogenesis of sepsis, explore potential biomarkers, provide effective molecular targets for its diagnosis and treatment of sepsis.
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Piroptose , Sepse , Humanos , Piroptose/genética , Sepse/diagnóstico , Sepse/genética , Apoptose , Algoritmos , Análise por ConglomeradosRESUMO
INTRODUCTION: Tanshinone I (Tan I) is one of the bioactive components of Salvia miltiorrhiza. Whether it inhibits gastric cancer through ferroptosis has not been reported. This study aimed to confirm the effect of Tan I on ferroptosis in gastric cancer cells. METHODS: AGS and HGC27 cells were treated with Tan I. First, oxidative stress-related parameters and the expression of ferroptosis-related proteins were examined. Combined with a ferroptosis inhibitor, Tan I was found to inhibit gastric cancer cells via the ferroptosis pathway. Finally, with bioinformatics analysis, the target protein of Tan I was identified. RESULTS: Tan I significantly inhibited the expression level of GPX4. This molecule also increased ROS, MDA, and Fe2+ contents and decreased GSH enzyme activity. Therefore, we hypothesized that Tan I may inhibit gastric cancer cells by inducing ferroptosis. Western blotting results showed that Tan I inhibited the expression levels of the ferroptosis resistance-related proteins GPX4, SLC7A11, and FTH1, while the pro-ferroptosis-related proteins TFR1 and ACSL4 were significantly upregulated. A ferroptosis inhibitor effectively reversed these regulatory effects of Tan I in gastric cancer. With these data combined with the bioinformatics analysis, KDM4D was identified as a key regulatory target of Tan I. Mechanistically, Tan I induced positive regulation of ferroptosis resistance-related indicators by inhibiting KDM4D to upregulate p53 protein expression. Overexpression of KDM4D significantly reversed the effect of Tan I-induced ferroptosis resistance in gastric cancer cells. CONCLUSIONS: Tan I induced ferroptosis inhibition in gastric cancer by regulating the KDM4D/p53 pathway.
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Ferroptose , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Proteína Supressora de Tumor p53 , Histona Desmetilases com o Domínio JumonjiRESUMO
Heat shock proteins (HSP) are a large family of peptide proteins that are widely found in cells. Studies have shown that the expression and function of HSPs in cells are very complex, and they can participate in cellular physiological and pathological processes through multiple pathways. Multiple heat shock proteins are associated with cancer cell growth, proliferation, metastasis, and resistance to anticancer drugs, and they play a key role in cancer development by ensuring the correct folding or degradation of proteins in cancer cells. As research hotspots, HSP90, HSP70 and HSP27 have been extensively studied in cancer so far. However, HSP20, also referred to as HSPB6, as a member of the small heat shock protein family, has been shown to play an important role in the cardiovascular system, but little research has been conducted on HSP20 in cancer. This review summarizes the current cellular functions of HSP20 in different cancer types, as well as its effects on cancer proliferation, progression, prognosis, and its other functions in cancer, to illustrate the close association between HSP20 and cancer. We show that, unlike most HSPs, HSP20 mainly plays an active anticancer role in cancer development, which is expected to provide new ideas and help for cancer diagnosis and treatment and research.
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Antineoplásicos , Neoplasias , Humanos , Proteínas de Choque Térmico/metabolismo , Neoplasias/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP20/metabolismoRESUMO
Contrast-induced acute kidney injury(CI-AKI) is the third cause of AKI. Although tubular injury has been regarded as an important pathophysiology of CI-AKI, the underlying mechanism remains elusive. Here, we found arginase2(ARG2) accumulated in the tubules of CI-AKI mice, and was upregulated in iohexol treated kidney tubular cells and in blood samples of CI-AKI mice and patients, accompanied by increased nitrosative stress and apoptosis. However, all of the above were reversed in ARG2 knockout mice, as evidenced by the ameliorated kidney dysfunction and the tubular injury, and decreased nitrosative stress and apoptosis. Mechanistically, HO-1 upregulation could alleviate iohexol or ARG2 overexpression mediated nitrosative stress. Silencing and overexpressing ARG2 was able to upregulate and downregulate HO-1 expression, respectively, while HO-1 siRNA had no effect on ARG2 expression, indicating that ARG2 might inhibit HO-1 expression at the transcriptional level, which facilitated nitrosative stress during CI-AKI. Additionally, CREB1, a transcription factor, bound to the promoter region of ARG2 and stimulated its transcription. Similar findings were yielded in cisplatin- or vancomycin-induced AKI models. Taken together, ARG2 is a crucial target of CI-AKI, and activating CREB1/ARG2/HO-1 axis can mediate tubular injury by promoting nitrosative stress, highlighting potential therapeutic strategy for treating CI-AKI.
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Injúria Renal Aguda , Iohexol , Humanos , Camundongos , Animais , Iohexol/efeitos adversos , Iohexol/metabolismo , Estresse Nitrosativo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/tratamento farmacológico , Rim/metabolismo , Fatores de Transcrição/metabolismo , Cisplatino/farmacologia , Apoptose , Camundongos Endogâmicos C57BLRESUMO
Objective: To analyze the application effect of damage control surgery (DCS) combined with seamless integrated rescue mode in emergency treatment of severe thoracic and abdominal trauma. Methods: The clinical data of 90 patients with severe thoracic and abdominal trauma admitted to the emergency room of our hospital from September 2020 to September 2021 were selected for the retrospective analysis. According to the different treatment methods, they were divided into the experimental group (EG) and the control group (CG), with 45 cases in each group. The CG was treated with seamless integrated rescue mode, and the EG received the DCS combined with seamless integrated rescue mode. The mortality, complication rate, mixed venous oxygen saturation (SvO2), cardiac index (CI), central venous pressure (CVP), prothrombin time (PT), active partial thromboplastin time (APTT), the content of arterial blood lactate (ABL), C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-10 (IL-10) were compared between the two groups. Results: Compared with the CG, after intervention, the levels of SvO2, CI, CVP, APTT and IL-10 in the EG were signally higher (all P < .05), while the levels of PT, ABL, CRP and IL-6 in the EG were memorably lower (all P < .05), and the mortality and complication rate in the EG were notably lower (all P < .05). Conclusion: The application of DCS combined with seamless integrated rescue mode in emergency treatment of patients with severe thoracic and abdominal trauma can effectively reduce the mortality of patients, improve their coagulation dysfunction, decrease the level of inflammatory factors and reduce the occurrence of complications, with a positive significance for improving disease prognosis.