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1.
Int J Nephrol ; 2021: 5497346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733559

RESUMO

Metabolic reprogramming originally referred to the ability of cancer cells to metabolically adapt to changes in environmental conditions to meet both energy consumption and proliferation requirements. According to recent studies, renal cells are also capable of reprogramming their metabolism after kidney injury, and these cells undergo different kinds of metabolic reprogramming in different kidney diseases. Metabolic reprogramming also plays a role in the progression and prognosis of kidney diseases. Therefore, metabolic reprogramming is not only a prominent feature but also an important contributor to the pathophysiology of kidney diseases. Here, we briefly review kidney diseases and metabolic reprogramming and discuss new ways to treat kidney diseases.

2.
Front Cell Dev Biol ; 9: 741060, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805150

RESUMO

Renal fibrosis is the most common pathological manifestation of a wide variety of chronic kidney disease. Increased extracellular matrix (ECM) secretion and enhanced microenvironment stiffening aggravate the progression of renal fibrosis. However, the related mechanisms remain unclear. Here, we evaluated the mechanism by which ECM stiffness aggravates renal fibrosis. In the present study, renal mesangial cells (MCs) were cultured on polyacrylamide hydrogels with different stiffness accurately detected by atomic force microscope (AFM), simulating the in vivo growth microenvironment of MCs in normal kidney and renal fibrosis. A series of in vitro knockdown and activation experiments were performed to establish the signaling pathway responsible for mechanics-induced MCs activation. In addition, an animal model of renal fibrosis was established in mice induced by unilateral ureteral obstruction (UUO). Lentiviral particles containing short hairpin RNA (sh RNA) targeting Piezo1 were used to explore the effect of Piezo1 knockdown on matrix stiffness-induced MCs activation and UUO-induced renal fibrosis. An in vitro experiment demonstrated that elevated ECM stiffness triggered the activation of Piezo1, which increased YAP nuclear translocation through the p38MAPK, and consequently led to increased ECM secretion. Furthermore, these consequences have been verified in the animal model of renal fibrosis induced by UUO and Piezo1 knockdown could alleviate UUO-induced fibrosis and improve renal function in vivo. Collectively, our results for the first time demonstrate enhanced matrix stiffness aggravates the progression of renal fibrosis through the Piezo1-p38MAPK-YAP pathway. Targeting mechanosensitive Piezo1 might be a potential therapeutic strategy for delaying the progression of renal fibrosis.

4.
J Chin Med Assoc ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34759210

RESUMO

BACKGROUND: Stress urinary incontinence (SUI) is a major health problem affecting approximately 50% of the female population over 45 years of age. We evaluated the therapeutic effects of a home-based non-invasive wireless sensor pelvic floor muscle training (PFMT) device with assisted Kegel exercise for SUI. METHODS: We included sixty women aged 40 to 60 years who were diagnosed with urodynamic SUI (mean pad test, 10.52 g). The PFMT device applicator was clamped on the upper inner thigh, and the patients could self-train at home. The signal was recorded and delivered to a 3G/4G smartphone via Bluetooth, which also allows guided feedback via the smartphone's voice. To evaluate the therapeutic effect, all patients completed the following questionnaires: a 3-day bladder diary, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the Urogenital Distress Inventory-Short Form (UDI-6-SF), and the Incontinence Impact Questionnaire-7 (IIQ-7). One-hour pad test measurements were performed before the test (M0) and at 1 (M1), 2 months (M2), and 3 months (M3) after the PFMT device-assisted Kegel exercise. RESULTS: The one-hour pad test and the scores of the ICIQ-SF, UDI-6, and IIQ-7 questionnaires were improved at M1, M2, and M3, compared with the M0 values. The mean value of the post-voiding residual urine (PVR) significantly decreased at M2 and M3. The subjective and objective improvement rates at M3 were 80% and 72%, respectively. CONCLUSION: The data demonstrated that 3 months of Kegel exercise assisted with a home-based PFMT device improved the number and severity of episodes, post-voiding residual urine, and quality of life (QoL) in patients with SUI, suggesting that this device might serve as an alternative non-invasive therapy for mild and moderate SUI.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34761489

RESUMO

The clinic prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT 4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT 4 A showed about 60-fold higher sonodynamic ROS generation in aggregation form than disaggregation form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The levels of AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle sizes of their aggregates. Moreover, biological studies demonstrated that ZnPcT 4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.

6.
Clin Immunol ; 232: 108876, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34740840

RESUMO

PURPOSE: To evaluate the efficacy and safety of immune checkpoint inhibitor combination therapy in advanced renal cell carcinoma (RCC). METHODS: We searched PubMed/Embase/Cochrane Library for relevant randomized controlled trials (RCTs). Clinical outcome measures including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and adverse events (AEs) were analyzed by Stata 15.1 software. RESULTS: Seven RCTs involving 3461 patients were included. The pooled hazard ratios of OS and PFS for combination therapy were 0.67 (0.53-0.82, p < 0.001) and 0.68 (0.52-0.83, p < 0.001), respectively. Longer OS and PFS for combination therapy was also observed in the PD-L1 expression leve ≥1% group. The pooled odds ratios of ORRs and grade 3 or higher AEs were 2.31 (1.61-3.32, p < 0.001) and 0.94 (0.65-1.37, p = 0.753), respectively. CONCLUSIONS: Immune checkpoint inhibitor combination therapy showed more clinical benefit in the first-line treatment for advanced RCC, with a safety profile.

7.
Taiwan J Obstet Gynecol ; 60(6): 1112-1115, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34794748

RESUMO

OBJECTIVE: Endometriosis-associated epithelial ovarian cancer (EOC) often includes clear cell carcinoma and endometrioid-type carcinoma. Due to the low incidence of primary mucinous EOC and absence of association between endometriosis and primary mucinous EOC, we present an unusual endometriosis-associated mixed mucinous and endometrioid adenocarcinoma arising from the same ovary. CASE REPORT: A 54-year-old woman had an abdominal palpable mass for months. Medical and surgical history, as well as preoperative surveys was unremarkable, except of presence of a pelvic mass. She underwent an exploration laparotomy, and a 22-cm right ovarian tumor was found. Grossly, right ovarian tumor containing brownish cloudy cystic fluid 2450 ml and an apparent 4 × 4 × 2 cm-sized papillary growth. Microscopically, a confluent glandular and infiltrative pattern presented endometrioid adenocarcinoma, and cells with intracytoplasmic mucin and stratified elongated epithelial cells presented mucinous adenocarcinoma. Surgico-pathological stage was FIGO IIIA due to tumor invading to the peritoneum above the pelvis. Postoperatively, the dose-dense chemotherapy was applied with uneventful outcome. CONCLUSION: This is a rare case, composed with mixed mucinous and endometrioid adenocarcinoma of the same ovary, suggesting that careful pathological diagnosis of endometriosis-associated EOC is needed.

8.
Taiwan J Obstet Gynecol ; 60(6): 1116-1120, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34794749

RESUMO

OBJECTIVE: Adult-type granulosa cell tumors (GCT) are sex cord-stromal tumors and often accompanied with abdominal distention and hyperestrogenism-related symptoms. Adult-type GCT-presenting ascites and pleural effusion is extremely rare. CASE REPORT: A 56-year-old perimenopausal woman presented with abdominal distention and abnormal vaginal spotting. Ultrasound and abdominal computed tomography showed a complex cystic mass in the left ovary accompanied with bilateral pleural effusion and ascites. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, left pelvic lymph node dissection, omentectomy and appendectomy. Final histopathological diagnosis was adult-type GCT. The patient had postoperative hormone and anti-angiogenesis agent therapy with free of disease. CONCLUSION: Ovarian cystic complex mass accompanied with ascites and pleural effusion often results from malignant ovarian tumors or benign ovarian fibroma. Based on the aforementioned report, the rare types of ovarian tumors, such as adult-type granulosa cell tumor of the ovary should be taken into consideration.

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13.
Neuroscience ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34762982

RESUMO

Morphine rewarding properties are the main reasons for drug-craving in behaviors occurring during morphine addiction. It has been suggested that morphine addiction relies on signals to the mesolimbic dopamine system, although the mechanisms outside the dopaminergic system are still unclear. Notably, the role of the dorsal raphe nucleus (DRN) serotoninergic (5-hydroxytryptamine, 5-HT) system remains unexplored. Using in vivo electrophysiological and optogenetic approaches, we found that morphine treatment increased DRN 5-TH neurons firing rate and optogenetic activation of DRN 5-HT neurons induced a rewarding effect, indicating that morphine reward is related to DRN 5-HT neurons. Accordingly, optogenetic inhibition of DRN 5-HT neurons following morphine injection reversed conditioned place preference (CPP) during chronic morphine treatment. These findings aid our understanding of the new functions of the DRN 5-HT neurons for morphine rewarding effect and provide a potential approach for the treatment of morphine addiction.

14.
Clin Ther ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34750020

RESUMO

PURPOSE: The prognosis of door to balloon time (DBT) after primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction (STEMI) has been extensively studied. However, the clinical implications of the ECG to activation time (EAT), as a component of DBT, on long-term outcomes are less well established. This study evaluates the association of EAT with major adverse cardiovascular events (MACEs) in more contemporary patients undergoing PPCI and investigates factors that influence EAT. METHODS: A total of 1082 consecutive patients with STEMI who underwent PPCI from 2013 to 2019 were classified into 3 groups according to EAT: EAT ≤30 minutes, EAT of 30 to 60 minutes, and EAT >60 minutes. We analyzed the incidence of MACEs, including all-cause death, nonfatal recurrence of MI, or nonfatal stroke during a median follow-up of 37 months. FINDINGS: The median EAT was 58 minutes (interquartile range, 44-80 minutes), which explained 90% of the variability in DBT and had the strongest correlation with DBT (r = 0.95, P < 0.001). Achieving an EAT of ≤30 minutes resulted in a 94.1% chance of achieving a DBT ≤90 minutes. The incidence of MACEs had a concurrent increase with increased EAT (10.2% for EAT ≤30 minutes, 14.3% for EAT of 30-60 minutes, and 17.3% for EAT >60 minutes; P = 0.027) that was driven by more mortality (4.2% for EAT ≤30 minutes, 6.9% for EAT of 30-60 minutes, and 9.8% for EAT >60 minutes; P = 0.020). An EAT >30 minutes was independently associated with risk-adjusted long-term MACEs (hazard ratio = 1.99; 95% CI, 1.07-3.69; P = 0.030). Critically ill status in emergency department (P = 0.001) and time required for consent of revascularization (P < 0.001) were significantly associated with delayed EAT. IMPLICATIONS: Achieving an EAT ≤30 minutes was key to achieving the guideline-recommended target time of DBT in contemporary practice. As a strong driver of overall DBT, EAT >30 minutes was associated with worse clinical outcome in patients with STEMI undergoing PPCI. These data suggest that efforts to minimize EAT are needed to reduce long-term MACEs in contemporary population. (Clin Ther. 2021;XX:XXX-XXX) © 2021 Elsevier HS Journals, Inc.

16.
Chem Rev ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609131

RESUMO

The applications of fluorinated molecules in bioengineering and nanotechnology are expanding rapidly with the controlled introduction of fluorine being broadly studied due to the unique properties of C-F bonds. This review will focus on the design and utility of C-F containing materials in imaging, therapeutics, and environmental applications with a central theme being the importance of controlling fluorine-fluorine interactions and understanding how such interactions impact biological behavior. Low natural abundance of fluorine is shown to provide sensitivity and background advantages for imaging and detection of a variety of diseases with 19F magnetic resonance imaging, 18F positron emission tomography and ultrasound discussed as illustrative examples. The presence of C-F bonds can also be used to tailor membrane permeability and pharmacokinetic properties of drugs and delivery agents for enhanced cell uptake and therapeutics. A key message of this review is that while the promise of C-F containing materials is significant, a subset of highly fluorinated compounds such as per- and polyfluoroalkyl substances (PFAS), have been identified as posing a potential risk to human health. The unique properties of the C-F bond and the significant potential for fluorine-fluorine interactions in PFAS structures necessitate the development of new strategies for facile and efficient environmental removal and remediation. Recent progress in the development of fluorine-containing compounds as molecular imaging and therapeutic agents will be reviewed and their design features contrasted with environmental and health risks for PFAS systems. Finally, present challenges and future directions in the exploitation of the biological aspects of fluorinated systems will be described.

17.
World J Clin Cases ; 9(25): 7453-7458, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34616811

RESUMO

BACKGROUND: Plasmacytoma is a rare neoplastic disorder that arises from B-lymphocytes. Solitary bladder plasmacytoma, a type of solitary extramedullary plasmacytoma, is even rarer. Treatments for solitary extramedullary plasmacytoma include surgery, chemotherapy, and radiation. However, there are no clinical trials or guidelines specifying which treatment might represent the gold standard. CASE SUMMARY: We herein report a case of a 51-year-old woman with solitary bladder plasmacytoma (SBP). There remains no consensus regarding the optimal treatment for SBP. However, we successfully treated her with transurethral resection of bladder tumor followed by postoperative radiotherapy (50 Gy/25 F). The patient remained free of tumor recurrence at a 7-mo follow-up. CONCLUSION: Radiation is the potential main treatment for SBP. However, surgery is also necessary.

18.
J Chin Med Assoc ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34610623

RESUMO

BACKGROUND: Cisplatin-based chemotherapy (CBC) is highly efficacious for advanced cervical cancer; its efficacy can be enhanced by combining with 15 mg/kg (standard dose) bevacizumab (BEV). However, this standard dose is associated with various adverse events. Therefore, in this retrospective study, we analyzed the survival outcomes and adverse events in patients with advanced or recurrent cervical cancer treated with CBC in combination with BEV 7.5 mg/kg. METHODS: Registered patient data were retrieved between October 2014 and September 2019, and 64 patients with advanced or recurrent cervical cancer treated with CBC+BEV (n=21) or CBC alone (n=43) were analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were the frequency and severity of adverse events (AEs). The Cox proportional-hazards model was applied to explore prognostic factors associated with PFS and OS. RESULTS: The 1-, 2-, and 3-year PFS rates (95% confidence interval (CI)) were 36.24% (22.0-50.5), 20.7% (9.8-34.2), and 17.7% (7.7-31.1) for the CBC group; and 71.4% (47.1-86.0), 51.0% (27.9-70.1), and 51.0% (27.9-70.1) for the CBC+BEV group, respectively. The 1-, 2-, and 3-year OS rates were 62.6% (46.4-75.18), 32.4% (18.8-46.9), and 23.2% (11.2-37.6) for the CBC group; and 85.7% (61.9-95.1), 66.6% (42.5-82.5), and 55.5% (27.1-76.7) for the CBC+BEV group, respectively. The CBC+BEV group presented higher PFS and OS rates, p=0.003 and p=0.005, respectively. Proteinuria (6 vs. 9, p=0.025) and hypertension (0 vs. 10, p<0.001) were less common, but anemia was more common in the CBC group (35 vs. 11, p=0.021). CONCLUSION: Overall, CBC+BEV significantly improved the PFS and OS compared with CBC alone. CBC+BEV also prevents severe adverse events and hence is an efficacious and safe therapeutic option.

19.
Cell Metab ; 33(10): 1957-1973.e6, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34614408

RESUMO

Skeletal aging is characterized by low bone turnover and marrow fat accumulation. However, the underlying mechanism for this imbalance is unclear. Here, we show that during aging in rats and mice proinflammatory and senescent subtypes of immune cells, including macrophages and neutrophils, accumulate in the bone marrow and secrete abundant grancalcin. The injection of recombinant grancalcin into young mice was sufficient to induce premature skeletal aging. In contrast, genetic deletion of Gca in neutrophils and macrophages delayed skeletal aging. Mechanistically, we found that grancalcin binds to the plexin-b2 receptor and partially inactivates its downstream signaling pathways, thus repressing osteogenesis and promoting adipogenesis of bone marrow mesenchymal stromal cells. Heterozygous genetic deletion of Plexnb2 in skeletal stem cells abrogated the improved bone phenotype of Gca-knockout mice. Finally, we developed a grancalcin-neutralizing antibody and showed that its treatment of older mice improved bone health. Together, our data suggest that grancalcin could be a potential target for the treatment of age-related osteoporosis.

20.
Front Neurosci ; 15: 689601, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594180

RESUMO

Hippocampal neurodegeneration is a consequence of excessive alcohol drinking in alcohol use disorders (AUDs), however, recent studies suggest that females may be more susceptible to alcohol-induced brain damage. Adult hippocampal neurogenesis is now well accepted to contribute to hippocampal integrity and is known to be affected by alcohol in humans as well as in animal models of AUDs. In male rats, a reactive increase in adult hippocampal neurogenesis has been observed during abstinence from alcohol dependence, a phenomenon that may underlie recovery of hippocampal structure and function. It is unknown whether reactive neurogenesis occurs in females. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by 7 or 14 days of abstinence. Immunohistochemistry (IHC) was used to assess neural progenitor cell (NPC) proliferation (BrdU and Ki67), the percentage of increased NPC activation (Sox2+/Ki67+), the number of immature neurons (NeuroD1), and ectopic dentate gyrus granule cells (Prox1). On day seven of abstinence, ethanol-treated females showed a significant increase in BrdU+ and Ki67+ cells in the subgranular zone of the dentate gyrus (SGZ), as well as greater activation of NPCs (Sox2+/Ki67+) into active cycling. At day 14 of abstinence, there was a significant increase in the number of immature neurons (NeuroD1+) though no evidence of ectopic neurogenesis according to either NeuroD1 or Prox1 immunoreactivity. Altogether, these data suggest that alcohol dependence produces similar reactive increases in NPC proliferation and adult neurogenesis. Thus, reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

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