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1.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1361-1368, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621984

RESUMEN

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cß(PKCßⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group. After drug administration for 7 consecutive days, the area of myocardial infarction in each group was measured. The pathological morphology of the myocardial tissue was observed by hematoxylin-eosin(HE) staining. The apoptosis in the myocardial tissue was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Enzyme-linked immunosorbent assay(ELISA) was employed to measure the le-vels of indicators of myocardial injury and oxidative stress. The level of ROS was detected by flow cytometry. The protein and mRNA levels of the related proteins in the myocardial tissue were determined by Western blot and real-time quantitative PCR(RT-qPCR), respectively. Compared with the sham group, the model group showed obvious myocardial infarction, myocardial structural disorders, interstitial edema and hemorrhage, presence of a large number of vacuoles, elevated levels of myocardial injury markers, myocardial apoptosis, ROS, and malondialdehyde(MDA), lowered superoxide dismutase(SOD) level, and up-regulated protein and mRNA le-vels of PKCßⅡ, NOX2, cysteinyl aspartate specific proteinase-3(caspase-3), and acyl-CoA synthetase long-chain family member 4(ACSL4) in the myocardial tissue. Compared with the model group, Chaihu Sanshen Capsules reduced the area of myocardial infarction, alleviated the pathological changes in the myocardial tissue, lowered the levels of myocardial injury and oxidative stress indicators and apoptosis, and down-regulated the mRNA and protein levels of PKCßⅡ, NOX2, caspase-3, and ACSL4 in the myocardial tissue. Chaihu Sanshen Capsules can inhibit oxidative stress and programmed cell death(apoptosis, ferroptosis) by regulating the PKCßⅡ/NOX2/ROS signaling pathway, thus mitigating myocardial ischemia reperfusion injury.


Asunto(s)
Infarto del Miocardio , Daño por Reperfusión Miocárdica , Daño por Reperfusión , Ratas , Animales , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/genética , Especies Reactivas de Oxígeno , Ratas Sprague-Dawley , Caspasa 3/metabolismo , Transducción de Señal , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/genética , ARN Mensajero , Apoptosis
2.
Ther Adv Infect Dis ; 11: 20499361241248058, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681967

RESUMEN

Background: Urosepsis is a common disease in urology, which is characterized by high treatment costs and high mortality. In the treatment of sepsis, anti-infection therapy is the most important means. However, the effect of empirical anti-infection therapy is often not ideal. Therefore, it is necessary to continuously monitor the prevalence of bacterial isolates in the blood culture of patients with urinary sepsis and their sensitivity to antibacterial drugs. This is of great significance to improve the efficacy of empirical antibiotic therapy for urosepsis. Objective: To elucidate the landscape of prevailing bacterial profiles and their antimicrobial susceptibilities in urosepsis cases, and to furnish robust clinical evidence to underpin the timely initiation of empirical antibiotic treatment. Methods: Collect the basic information and blood culture results of patients with urosepsis hospitalized from 2017 to 2020. Retrospective analysis of bacterial species and antimicrobial susceptibility in urosepsis and changes over 4 years. Results: Gram-negative bacteria (178 isolates, 75.11%) constituted the main pathogens causing urosepsis, followed by Gram-positive bacteria (46 isolates, 19.41%) and fungus (13 isolates, 5.48%). The sensitivity of ertapenem, meropenem, amikacin, and imipenem to Gram-negative bacteria all exceeded 85%. The sensitivity rates of levofloxacin, gentamicin, and ciprofloxacin are decreasing every year (p < 0.05). Tigecycline, vancomycin, and linezolid exhibited excellent sensitivity against Gram-positive bacteria. Among fungi, fluconazole demonstrated universal sensitivity, while itraconazole-resistant isolates have been found, and amphotericin B is still effective. Conclusion: Analysis of blood culture results of patients more accurately reflected the etiology of urosepsis, mainly Escherichia coli, Enterococcus, and Klebsiella pneumoniae. If there are no definitive blood culture results, empiric treatment of urosepsis should not include fluoroquinolone antibiotics. Cefepime, cefoxitin, and ceftazidime are the most sensitive antibiotics to Gram-negative bacteria besides carbapenem antibiotics. In addition, the current situation regarding extended-spectrum ß-lactamase-producing bacteria and carbapenem-resistant Enterobacteriaceae bacteria resistance is extremely concerning with limited therapeutic options available. Strengthening antibiotic management practices and exploring novel antibacterial agents can help mitigate this issue.

3.
J Nanobiotechnology ; 22(1): 129, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528554

RESUMEN

The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.


Asunto(s)
Aterosclerosis , Emodina , Iridoides , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/tratamiento farmacológico , Liposomas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Emodina/farmacología , Emodina/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Colesterol
6.
Asian J Surg ; 47(2): 1019-1020, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37985323
7.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5623-5631, 2023 Oct.
Artículo en Chino | MEDLINE | ID: mdl-38114155

RESUMEN

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.


Asunto(s)
Enfermedad Coronaria , Función Ventricular Izquierda , Ratas , Animales , Volumen Sistólico , Ratas Sprague-Dawley , Enfermedad Coronaria/tratamiento farmacológico , Metabolómica
8.
J Endourol ; 37(12): 1241-1247, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37756365

RESUMEN

Introduction: Percutaneous nephrolithotomy (PCNL) is the recommended treatment for 2-4-cm renal stones. Minimally invasive PCNL (MPCNL) with ≤22F sheath was frequently used instead of standard PCNL. MPCNL uses pressurized irrigation to flush out stone fragments through a conventional nephrostomy sheath (cNS), which may result in higher intrarenal pressure (IRP) and longer operating time. The novel vacuum-assisted nephrostomy sheath (vaNS) was developed to mitigate higher IRP and to facilitate stone removal. It might improve the performance of MPCNL. This prospective and randomized trial compares these two sheaths. Materials and Methods: In total, 120 patients with 2-4-cm renal stones were accrued in six tertiary medical centers with equal numbers in 2021. In total, 120 patients underwent mPCNL, 60 using 18F cNS and 60 using 18F vaNS, in a prospective and randomized assignment. The primary outcome measurement is decrease in IRP. The secondary outcome is efficacy in stone retrieval. Results: The IRP was lower with vaNS than with cNS: mean IRP during lithotripsy was 12.0 ± 2.7 mm Hg with vaNS vs 20.4 ± 6.0 mm Hg with cNS, p = 0.000. IRP duration ≥30 mm Hg was shorter with vaNS than with cNS (6.7 ± 7.4 seconds vs 113.4 ± 222.7 seconds, p = 0.001). vaNS has shorter stone removal time (26.9 ± 14.3 minutes vs 35.7 ± 11.8 minutes, p = 0.000). Stone extraction rate was higher (166.4 ± 88.1 mm3/min vs 90.4 ± 31.7 mm3/min, p = 0.000). Stone grasper usage was less (1.4 ± 2.6 vs 11.9 ± 9.7, p = 0.000). vaNS maintained the safety profile. Blood loss, creatinine changes, perioperative complications, and hospital stays were the same in both groups, all p > 0.05. Conclusion: MPCNL for stones 2-4 cm using vaNS has shorter stone removal time, higher stone extraction rate, and less use of stone extractor. vaNS is superior to cNS at reducing IRP and is associated with improved stone free rates at 3 days but not at 30 days postoperatively. The trial was registered with Chinese Clinical Trial Registry (ClinicalTrials.gov, NCT ChiCTR2000039681).


Asunto(s)
Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Cálculos Renales/cirugía
9.
Cell Signal ; 112: 110887, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37717713

RESUMEN

Sirtuin1 (Sirt1) activation significantly attenuated calcium oxalate (CaOx) crystal deposition and renal inflammatory injury by regulating renal immune microenvironment. Here, to elucidate the molecular mechanism underlying the therapeutic effects of Sirt1 on macrophage related inflammation and tubular epithelial cells (TECs) necrosis, we constructed a macrophage and CaOx monohydrate (COM)-stimulated tubular cell co-culture system to mimic immune microenvironment in kidney and established a mouse model of CaOx nephrocalcinosis in wild-type and myeloid-specific Sirt1 knockout mice. Target prediction analyses of Gene Expression Omnibus Datasets showed that only miR-34b-5p is regulated by lipopolysaccharides and upregulated by SRT1720 and targets the TLR4 3'-untranslated region. In vitro, SRT1720 suppressed TLR4 expression and M1 macrophage polarization and decreased reactive oxygen species (ROS) production and mitochondrial damage in COM-stimulated TECs by targeting miR-34b-5p. Mechanically, Sirt1 promoted miR-34b-5p expression by suppressing the tri-methylation of H3K27, which directly bound to the miR-34b-5p promoter and abolished the miR-34b-5p transcription. Furthermore, loss of Sirt1 aggravated CaOx nephrocalcinosis-induced inflammatory and oxidative kidney injury, while AgomiR-34b reversed these effects. Therefore, our data suggested that Sirt1 inhibited TLR4 signaling and M1 macrophage polarization and decreased inflammatory and oxidative injury of TECs in vitro and in vivo.


Asunto(s)
MicroARNs , Nefrocalcinosis , Ratones , Animales , Oxalato de Calcio/metabolismo , Oxalato de Calcio/farmacología , Nefrocalcinosis/metabolismo , Sirtuina 1/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Riñón/metabolismo , Macrófagos/metabolismo
10.
Medicine (Baltimore) ; 102(36): e35006, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37682146

RESUMEN

BACKGROUND: Chronic heart failure (CHF) is a common and difficult-to-treat disease in clinical practice. The efficacy and safety of Zhenyuan capsule (ZYC) in the treatment of CHF were evaluated by meta-analysis and trial sequential analysis (TSA) of published relevant data. METHODS: Searched 8 databases for clinical literature on ZYC in the treatment of CHF, up to December 2022. Then the meta-analysis and TSA were performed on the studies that met the inclusion criteria. RESULTS: Meta-analysis showed that compared with conventional treatment, combined use of ZYC could significantly increase the clinical effective rate (risk ratio 1.20, 95% confidence interval [CI] 1.14~1.26, P < .00001) by 20%, left ventricular ejection fraction (MD 8.85, 95%CI 4.57~13.12, P < .0001) by 8.85%, and 6-minutes walking distance (MD 47.91, 95%CI 18.66~77.17, P = .001) by 47.91 m, and significantly reduce brain natriuretic peptide (MD -247.86, 95%CI -330.62~-165.09, P < .00001) by 247.86 pg/mL. TSA showed that the benefits suggested by the original results were conclusive. In terms of safety, the total adverse events in the combined group of ZYC were comparable to those in the conventional group, and TSA demonstrated that this result needed more research and demonstration. CONCLUSION: ZYC can effectively improve the clinical efficacy of treating CHF, significantly increase left ventricular ejection fraction and 6-minute walk distance, and remarkably reduce brain natriuretic peptide. ZYC, with definite efficacy and safety, has the value of clinical application and in-depth research.


Asunto(s)
Insuficiencia Cardíaca , Péptido Natriurético Encefálico , Humanos , Péptido Natriurético Encefálico/uso terapéutico , Volumen Sistólico , Función Ventricular Izquierda , Enfermedad Crónica , Insuficiencia Cardíaca/tratamiento farmacológico
11.
Int. braz. j. urol ; 49(4): 441-451, July-Aug. 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1506403

RESUMEN

ABSTRACT Background: Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). We performed this meta-analysis to investigate whether PFME during the entire perioperative period, including before and after RP, can significantly improve the recovery of postoperative UI. Methods: We systematically reviewed randomized controlled trials (RCT) from PubMed, Medline, web of science, Cochrane library, and clinicalitrials.com prior to October 2022. Efficacy data were pooled and analyzed using Review Manager Version 5.3. Pooled analyses of urinary incontinence rates 1, 3, 6, and 12 months postoperatively were conducted, using odds ratio (OR) and 95% confidence intervals (CIs). Results: We included a total of 15 RCT studies involving 2178 patients received RP. Postoperative UI could be improved after 1 month, 3 months and 6 months, and the OR were 0.26 (95%CI:0.15-0.46) 0.30 (95%CI: 0.11-0.80) 0.20 (95%CI: 0.07- 0.56) in postoperative PFME group compared to no PFME group. However, there was no significant difference between the two groups in 12 months after surgery, and the OR was 0.85(95%CI: 0.48,1.51). There were similar results in perioperative PFME group compared to no PFME group with the OR of 0.35 (95%CI: 0.12, 0.98) and 0.40 (95%CI: 0.21, 0.75) in 1 and 3 months after surgery. Our results indicated no significant difference between perioperative PFME group and postoperative PFME group. The OR was 0.58 (95%CI: 0.20-1.71) 0.58 (95%CI:0.20-0.71) and 0.66 (95%CI: 0.32-1.38) in 1, 3 and 6 months after surgery. Conclusion: Application of PFME after RP significantly reduced the incidence of early postoperative UI, and additional preoperative PFME had no significant improvement on the recovery of UI.

13.
Int Braz J Urol ; 49(4): 441-451, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37267610

RESUMEN

BACKGROUND: Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). We performed this meta-analysis to investigate whether PFME during the entire perioperative period, including before and after RP, can significantly improve the recovery of postoperative UI. METHODS: We systematically reviewed randomized controlled trials (RCT) from PubMed, Medline, web of science, Cochrane library, and clinicalitrials.com prior to October 2022. Efficacy data were pooled and analyzed using Review Manager Version 5.3. Pooled analyses of urinary incontinence rates 1, 3, 6, and 12 months postoperatively were conducted, using odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: We included a total of 15 RCT studies involving 2178 patients received RP. Postoperative UI could be improved after 1 month, 3 months and 6 months, and the OR were 0.26 (95%CI:0.15-0.46) 0.30 (95%CI: 0.11-0.80) 0.20 (95%CI: 0.07- 0.56) in postoperative PFME group compared to no PFME group. However, there was no significant difference between the two groups in 12 months after surgery, and the OR was 0.85(95%CI: 0.48,1.51). There were similar results in perioperative PFME group compared to no PFME group with the OR of 0.35 (95%CI: 0.12, 0.98) and 0.40 (95%CI: 0.21, 0.75) in 1 and 3 months after surgery. Our results indicated no significant difference between perioperative PFME group and postoperative PFME group. The OR was 0.58 (95%CI: 0.20-1.71) 0.58 (95%CI:0.20-0.71) and 0.66 (95%CI: 0.32-1.38) in 1, 3 and 6 months after surgery. CONCLUSION: Application of PFME after RP significantly reduced the incidence of early postoperative UI, and additional preoperative PFME had no significant improvement on the recovery of UI.


Asunto(s)
Diafragma Pélvico , Incontinencia Urinaria , Humanos , Masculino , Terapia por Ejercicio/métodos , Próstata , Prostatectomía/efectos adversos , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & control
14.
Front Immunol ; 14: 1181688, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37377966

RESUMEN

Objective: To study the effect of an injection of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on inflammation and immune function in patients with upper urinary tract calculi complicated by infection who have undergone percutaneous nephrolithotomy. Methods: We retrospectively recorded the clinical data of patients with upper urinary tract calculi complicated by infection who have undergone Percutaneous nephrolithotomy(PCNL) in the Department of Urology, 2nd Affiliation Hospital of Kunming Medical University, from March to December 2021. Clinical data include general condition, laboratory index, CT, postoperative body temperature, heart rate, respiration, SIRS, sepsis, etc. Patients were divided into treated and control groups according to whether they had received a preoperative PA-MSHA injection. The two groups were compared for indices of inflammation and complications of infection after PCNL. Pre- and post-operative lymphocyte subsets and immunoglobulin changes were compared. Results: 115 patients were included in the study, including 43 in the treatment group and 72 in the control group. After Propensity Score Matching, 90 patients were divided into treatment (n=35) and control (n=55) groups. The postoperative inflammation index was higher in the treatment group than in the control group (P<0.05). The incidence of postoperative SIRS was higher in the treatment group than control (P<0.05). There were no cases of sepsis in either group. The double-positive T cells lymphocyte subsets were higher in the treatment group than in the control group ((P<0.05). Pre- and post-operative changes in immune function: total T lymphocyte count reduced, NK and NKT cell count increased in the control group, double-positive T cell count increased in the treatment group, IgG, IgA, IgM, complement C3 and C4 count reduced in both groups post-operatively. Conclusion: This study found that patients with upper urinary tract calculi and infection treated with antibiotic-based PA-MSHA before percutaneous nephrolithotomy had an increased inflammatory response after surgery, which may play a role in the prevention and treatment of sepsis. The percentage of double-positive T cells in the peripheral blood was increased after PA-MSHA treatment, which may have an immunomodulatory and protective effect in PCNL patients with stones complicated by infection.


Asunto(s)
Cálculos Renales , Nefrolitotomía Percutánea , Sepsis , Sistema Urinario , Humanos , Nefrolitotomía Percutánea/efectos adversos , Hemaglutininas , Manosa , Pseudomonas aeruginosa , Estudios Retrospectivos , Sepsis/etiología , Inflamación/etiología , Inmunidad
15.
Int. braz. j. urol ; 49(3): 281-298, may-June 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1440247

RESUMEN

ABSTRACT Background Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis. Materials and Methods PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software. Results A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results. Conclusions The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.

16.
J Nanobiotechnology ; 21(1): 158, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37208681

RESUMEN

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.


Asunto(s)
Aterosclerosis , Proproteína Convertasa 9 , Ratones , Animales , Proproteína Convertasa 9/metabolismo , Liposomas , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo
18.
Int Braz J Urol ; 49(3): 281-298, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37115175

RESUMEN

BACKGROUND: Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis. MATERIALS AND METHODS: PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software. RESULTS: A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results. CONCLUSIONS: The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.


Asunto(s)
Cálculos Urinarios , Urolitiasis , Humanos , Femenino , Masculino , Índice de Masa Corporal , Sobrepeso/complicaciones , Oxalato de Calcio , Ácido Úrico , Urolitiasis/etiología , Obesidad/complicaciones
19.
Zhongguo Zhong Yao Za Zhi ; 48(4): 879-889, 2023 Feb.
Artículo en Chino | MEDLINE | ID: mdl-36872258

RESUMEN

Acute myocardial infarction seriously endangers the health of people due to its high morbidity and high mortality. Reperfusion strategy is the preferred treatment strategy for acute myocardial infarction. However, reperfusion may lead to additional heart damage, namely myocardial ischemia reperfusion injury(MIRI). Therefore, how to reduce myocardial ischemia reperfusion injury has become one of the urgent problems to be solved in cardiovascular disease. Traditional Chinese medicine(TCM) has the multi-component, multi-channel, and multi-target advantages in the treatment of MIRI, which offers new ideas in this aspect. TCM containing flavonoids has a variety of biological activities and plays a significant role in the treatment of MIRI, which has great research and development application value. TCM containing flavonoids can regulate multiple signaling pathways of MIRI, such as phosphatidylinositol 3 kinase/kinase B(PI3K/Akt) signaling pathway, Janus kinase/signal transducer and activator of transcriptions(JAK/STAT) signaling pathway, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, nuclear factor-erythroid 2-related factor 2/antioxidant response element(Nrf2/ARE) signaling pathway, nuclear factor kappa-B(NF-κB) signaling pathway, silent information regulator 1(Sirt1) signaling pathway, and Notch signaling pathway. It reduces MIRI by inhibiting calcium overload, improving energy metabolism, regulating autophagy, and inhibiting ferroptosis and apoptosis. Therefore, a review has been made based on the regulation of relative signaling pathways against MIRI by TCM containing flavonoids, thus providing theoretical support and potential therapeutic strategies for TCM to alleviate MIRI.


Asunto(s)
Daño por Reperfusión Miocárdica , Humanos , Fosfatidilinositol 3-Quinasas , Transducción de Señal , FN-kappa B , Proteínas Quinasas Activadas por AMP , Flavonoides
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