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The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson's disease (PD) found in pathological studies is the "rostrocaudal gradient," which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value < 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.
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This study examines the presence of bacterial contamination on surgical gloves and suggests appropriate measures for an aseptic surgical environment. To prevent glove contamination during surgery, surgeons and assistants should change gloves periodically, and scrub nurses should be careful when opening packages and handing over implants.
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Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents, including n-hexane (EHex), chloroform (ECHCl3), ethyl acetate (EEA), n-butyl alcohol (EBuOH), and water (EDW). Ethyl acetate fraction (EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-and di-glycoside of each aglycone. The main flavonol form of EEA is the mono-glycoside of each aglycone detected, and the most abundant flavonol mono-glycoside is kaempferol 3-glucoside 7.4%, followed by quercetin-3-glucoside 2.3% and isorhamnetin 3-glucoside 1.4%. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that the flavonol composition of E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.
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BACKGROUND: Cancer is one of the leading causes of death in most countries with an expected increased burden on healthcare systems. Since integrative medical treatments are not collected within the scope of existing cancer registries, the establishment of the Korean Medicine Cancer Registry (KMCARE), gathering integrative therapies, including conservative care and Korean medicine, is warranted. METHODS: A prospective observational study based on the registry will be conducted in 5 Korean medical hospitals. A total of 650 eligible participants undergoing Korean medicine treatments within 1 month of a diagnosis of lung, colorectal, stomach, or breast cancer are anticipated to be enrolled in the registry. Data collected in the KMCARE can be classified into patient information, received treatments, and outcomes. The primary outcome is the Functional Assessment of Cancer Therapy-General Questionnaire score at 3 months. Secondary outcomes include the MD Anderson Symptom Inventory-Core and the Body Constitution Questionnaire at 3 and 6 months. After 6 months of follow-up periods, survival surveillance will be continued for additional 18 months. Descriptive and statistical analysis of primary and secondary outcomes, baseline data, safety, survival, and prognostic factors will be performed. DISCUSSION: This is the first prospective, multi-centered, registry-based observational study of cancer patients in Korean medicine hospitals, which could reveal the current status of cancer patients receiving integrative cancer therapies, and provide better insight into the role of Korean medicine in palliative care for patients with cancer. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0007447.
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Neoplasias , Projetos de Pesquisa , Humanos , Estudos Prospectivos , Sistema de Registros , Neoplasias/terapia , República da Coreia/epidemiologiaRESUMO
Dislocation after a total hip arthroplasty occurs in approximately 1% of patients; however, the frequency is much higher after revision surgery. To prevent dislocation, use of a larger femoral head is recommended, and a dual mobility femoral head has been introduced. However, reducing the dual mobility femoral head to the acetabular component is difficult in cases involving contracture in the soft tissue around the joint. A 72-year-old male patient who developed a periprosthetic joint infection underwent two-stage revision surgery using MUTARS®. Two months after the revision, the hip joint became dislocated and manual reduction was attempted; however, dislocation occurred again. During another revision using a dual mobility bearing, the soft tissue around the hip joint was too tight to reduce. The problem was overcome by first repositioning the dual mobility head into the acetabular socket, followed by assembly of the diaphyseal portion of the implant.
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Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists-BMK-C203 and BMK-C205-and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.
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Hormônio Liberador da Corticotropina , Elétrons , Camundongos , Animais , Sítios de Ligação , Descoberta de Drogas , Lasers , Cristalografia por Raios XRESUMO
Nitric oxide (NO) is an important gaseous signaling molecule in various physiological processes, which functions through interactions with its acceptor molecules located in organelles. NO has an extremely short half-life, making it challenging to experimentally achieve effective NO levels in organelles to study these interactions. Here we developed an organelle-specific, peptide-based NO delivery material that targets the nucleus. NO was attached to the SH group of a cysteine residue inserted into the N-terminus of a cell-penetrating peptide (CPP) conjugated to varying repeats of the nuclear localization signal (NLS), which we denoted NO-CysCPP-NLS, through S-nitrosylation. NO-CysCPP-NLS strongly induced osteogenic differentiation of mesenchymal stem cells. This delivery concept can be extended to cells other than stem cells to elucidate the effects of NO release in the nucleus. Furthermore, conjugation of NO to CysCPP fused to mitochondria- or lysosome-targeting signals can be used to deliver NO to other organelles such as mitochondria and lysosomes, respectively.
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Peptídeos Penetradores de Células , Células-Tronco Mesenquimais , Humanos , Osteogênese , Óxido Nítrico/farmacologia , Diferenciação Celular , Peptídeos Penetradores de Células/farmacologia , Peptídeos Penetradores de Células/química , Sinais de Localização Nuclear/química , Sinais de Localização Nuclear/farmacologia , Fatores Imunológicos/farmacologiaRESUMO
This study aimed to investigate the long-term clinical efficacy of and satisfaction with integrative Korean medicine (KM) treatment in patients with shoulder osteoarthritis (SOA). We conducted a prospective observational study of patients with SOA. Patients aged 19 years and older who underwent inpatient treatment for more than 1 week were eligible for enrollment in the study. The primary evaluation index was the numeric rating scale for shoulder pain. Sub-evaluation indices included the Shoulder Pain and Disability Index for shoulder function, EuroQol-5-dimension score for overall quality of life, and Patient Global Impression of Change. Outcome measures were assessed at admission, discharge, and follow-up. For the follow-up questionnaire survey, the following information was collected: current status, surgery after discharge, reasons for finding integrative KM treatment satisfactory/unsatisfactory, and quality of life after discharge. In total, 186 patients were enrolled in the primary analysis, and 103 patients completed the follow-up survey. The mean number of days of follow-up was 1019â ±â 439. Compared with the baseline, the mean differences in the numeric rating scale and Shoulder Pain and Disability Index were 3.05â ±â 0.34 and 36.06â ±â 5.53, respectively. Regarding the Patient Global Impression of Change, 89 out of 103 (86.4%) patients chose "minimally improved" or better. Furthermore, the EuroQol-5-dimension score also increased, showing an improvement of health-related quality of life after treatment. Integrative KM treatment is a potential option for reducing pain severity and improving function and health-related quality of life in patients with SOA. Prospective randomized studies would support this finding for the next step.
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Pacientes Internados , Osteoartrite , Humanos , Seguimentos , Qualidade de Vida , Estudos Prospectivos , Dor de Ombro/terapia , Ombro , Osteoartrite/terapia , República da CoreiaRESUMO
BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson's disease (PD), but little is known about the long-term benefit. OBJECTIVE: To investigate the survival rate and long-term outcome of DBS. METHODS: We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed. RESULTS: The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson's Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation. CONCLUSION: STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Doença de Parkinson/cirurgia , Período Pós-Operatório , Núcleo Subtalâmico/fisiologia , Resultado do TratamentoRESUMO
Background: Insomnia is one of the most prevalent cancer-related symptoms and has a severe impact on the quality of life. This study aimed to evaluate the efficacy and safety of traditional herbal medicine (THM) for improving sleep quality in patients with cancer. Methods: Randomized controlled trials (RCTs) evaluating orally administered THM in a cancer population with insomnia were searched using nine electronic databases up to November 30, 2020. The outcome measurements were sleep quality measured by validated questionnaire such as the Pittsburgh Sleep Quality Index (PSQI), total effective rate, and adverse effects. The included studies were appraised using the Cochrane risk of bias tool and meta-analyzed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Results: Fourteen RCTs were included in the systematic review, and 10 RCTs were analyzed quantitatively. Compared to hypnotics, THM showed a significant improvement in sleep quality by reducing the PSQI score [mean difference (MD) -2.25, 95% confidence interval (CI) -3.46 to -1.05, I 2 = 84%] and increasing the total effective rate [risk ratio (RR) 1.26, 95% CI 1.07 to 1.48, I 2 = 70%] with low quality of evidence. Compared to placebo, THM also reduced the PSQI score significantly (MD -2.56, 95% CI -3.81 to -1.31, I 2 = 91%) with moderate quality of evidence. The most frequently used herbs were Ziziphus jujuba Mill. No serious adverse events were observed. Conclusion: This review suggests that THM may be an effective therapeutic option for insomnia in patients with cancer. However, considering the limited methodological qualities and inconsistent results of the included trials, further rigorous RCTs are required. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], PROSPERO 2021 [CRD42021265070].
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Background: Radiation-induced dermatitis (RID) is a common complication of radiation therapy (RT). Although it has a high prevalence and can even trigger the premature end of conventional cancer therapies, there is no standard management. This study aims to evaluate whether topical use of Jaungo (Shiunko), a traditional herbal ointment mainly composed of Lithospermi radix and Angelica sinensis, could reduce RID compared to the water-in-oil type non-steroidal moisturizer in patients with breast cancer. Methods: This is a prospective, single-blinded, randomized controlled pilot trial that investigates the effect of topical application of Jaungo for the prevention of RID in postoperative breast cancer patients scheduled for RT, in comparison with the non-steroidal moisturizer, with a random distribution of 50 patients across the two groups. RT will be administered for 5-7 weeks with a biological equivalent dose (BED10) of 60 Gy or more, and the interventions will be applied 3 times a day during RT duration. Participants will be assessed a total of nine times, including eight visits during the period of RT and one visit at a 2-week follow-up period after the end of treatment. The incidence and severity of RID, quality of life, skin reaction symptoms, and maximum pain related to RID will be measured. The incidence rate of grade 2 or higher RID using the Radiation Therapy Oncology Group (RTOG) in the two groups will be statistically compared as the primary outcome. The types and frequencies of adverse events will be also collected and evaluated. All assessments will be performed by independent radiology oncologists. Discussion: This trial is currently ongoing and is recruiting. This study will determine the preventive efficacy of Jaungo in RID with postoperative breast cancer patients and provide evidence in traditional Korean medicine clinical practice.
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PURPOSE: Sipjeondaebo-tang (SDT) is a widely used traditional herbal medicine for relieving fatigue. This randomized, placebo-controlled, preliminary study evaluated SDT for cancer-related fatigue, which is the most common symptom experienced by patients with cancer. PATIENTS AND METHODS: Patients with a Brief Fatigue Inventory (BFI) score of at least 4 were randomly assigned in a double-blinded manner to receive SDT (3 g 3 times daily) or placebo orally for 3 weeks. The BFI was the primary outcome measure and secondary outcome measures included the Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ-C30), immunoregulatory tests, and safety. RESULTS: A total of 50 participants were randomly assigned and 48 patients completed the trial. Based on intention-to-treat analysis, fatigue, which was the primary outcome, was improved in both arms compared with the baseline, and was significantly better in the SDT group than in the placebo group at week 3 (3.56 ± 1.18 vs 4.63 ± 1.83, P = .019). Secondary outcomes, including anxiety, depression, and immunoregulatory tests, did not improve significantly in either group. However, quality of life measured using the EORTC QLQ-C30 improved in both arms compared with the baseline, and the global health subscale was significantly better in the SDT group than in the placebo group (P = .02). No significant toxicities were observed. CONCLUSION: SDT may improve cancer-related fatigue and quality of life in patients with cancer. A further randomized clinical trial with large sample size is warranted.
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Medicamentos de Ervas Chinesas , Neoplasias , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Medicina Herbária , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a major health burden in many countries. This review aimed to evaluate the efficacy of traditional herbal medicine (THM) combined with first-line platinum-based chemotherapy (PBCT) for the treatment of advanced NSCLC. METHODS: From inception to April 2021, relevant studies were retrieved from 9 electronic databases. Randomized controlled trials (RCTs) comparing survival outcomes of THMâ+âPBCT treatment with PBCT treatment in patients with advanced NSCLC were reviewed. The risk of bias was evaluated using the Cochrane Risk of Bias Tool. Overall survival, 1-year survival, progression-free survival or time to progression, tumor response rate, and adverse effects were analyzed. RESULTS: Sixteen RCTs comprising 1445 patients were included. The meta-analysis indicated that THMâ+âPBCT treatment, compared to PBCT alone, could improve overall survival (median survival ratioâ=â1.24, 95% confidence intervals [CI] [1.11, 1.39], Pâ<â.001), progression-free survival/time to progression (median survival ratioâ=â1.22, 95% CI [1.09, 1.37], Pâ<â.001), and the 1-year survival rate (risk ratio [RR]â=â1.56, 95% CI [1.31, 1.86], Pâ<â.001). THMâ+âPBCT also led to a higher tumor response rate (RRâ=â1.39, 95% CI [1.22, 1.59], Pâ<â.001) and lower incidence of thrombocytopenia (RRâ=â0.72, 95% CI [0.56, 0.92], Pâ=â.009) and nausea/vomiting (RRâ=â0.35, 95% CI [0.21, 0.57], Pâ<â.001), while there was no significant effect observed on leukopenia (RRâ=â0.68, 95% CI [0.34, 1.36], Pâ=â.27). CONCLUSION: THM, when used in combination with PBCT, might increase survival and the tumor response rate while decreasing the side effects caused by chemotherapy in patients with advanced NSCLC. However, considering the limited methodological qualities of the included trials, more rigorous RCTs are needed.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Tratamento Farmacológico/normas , Medicina Tradicional/normas , Platina/farmacologia , Tratamento Farmacológico/métodos , Humanos , Medicina Tradicional/métodos , Platina/uso terapêutico , Intervalo Livre de Progressão , Análise de SobrevidaRESUMO
OBJECTIVE: The purpose of this study is both to estimate the efficacy and the safety of Yukgunja-tang (YGJT) and to establish evidence for the use of herbal medicines in the management of patients with cancer-related anorexia. METHODS: We enrolled 40 patients with cancer-related anorexia. The enrolled participants were randomly allocated to 2 groups: the control group (n = 20), which received nutrition counseling, and the treatment group (n = 20), which received nutrition counseling and was administered YGJT at twice a day for 4 weeks (a total of 56 times @ 3.0 g each time). The primary outcome of this study was the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes were the FAACT score with the ACS score excluded, the score on the Visual Analog Scale (VAS) for appetite, and the results on laboratory tests regarding appetite, such as leptin, tumor necrosis factors (TNF-α), interleukin-6 (IL-6), and ghrelin. All variables related to the safety assessment, such as vital signs, electrocardiography results, laboratory test results (complete blood cell count, chemistry, urine test), and adverse events, were documented on the case report form (CRF) at every visit. RESULT: The difference in the primary outcome, that is, the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), between the control and the treatment groups was statistically significant (P = .023) as was the difference in the FAACT scores with the ACS score excluded, a secondary outcome, between the 2 groups; however, no statistically significant differences were noted in the scores on the VAS or the levels of leptin, TNF-α, IL-6, and ghrelin. In addition, no significant differences in the numbers and the types of adverse events or in the results on the laboratory tests between the control and the treatment groups were recorded. CONCLUSION: These results obtained in this research confirmed the efficacy and the safety of using YGJT as a herb-medicine treatment option for patients with cancer-related anorexia.
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Anorexia , Neoplasias , Anorexia/tratamento farmacológico , Anorexia/etiologia , Apetite , Caquexia , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Projetos PilotoRESUMO
Glioblastoma (GBM) is an aggressive brain tumor with a strong tendency of relapse and resistance to chemotherapy, but we currently lack non-toxic agents that effectively treat GBM. In this study, high-throughput screening of FDA-approved drugs was performed to identify safe and effective molecules and test their effect on GBM cell lines, LN229, U87 and T98G. Cough suppressants, oxelaidin and butamirate inhibited GBM growth. A Ras family GTPase, Ras-related associated with diabetes (RRAD), contributes to activation of STAT3, which is essential for survival and growth of many cancer types. Interestingly, oxelaidin and butamirate did not affect proliferation in RRAD negative GBM cells. Docking simulation analyses revealed selective interactions between oxelaidin and RRAD. The mechanism by which butamirate and oxelaidin inhibits GBM cell growth involves the suppression of STAT3 transcriptional activity, leading to down-regulation of cyclin D1 and survivin. In addition, components of RRAD-associated signaling cascades, including p-EGFR, p-Akt, and p-STAT3, were inhibited upon oxelaidin treatment. Intraperitoneal administration of oxelaidin or butamirate markedly suppressed tumor growth in a glioblastoma xenograft mouse model without significant adverse effects. Our collective findings indicate that oxelaidin and butamirate exert anti-tumor effects in glioblastoma, supporting its utility as a novel therapeutic candidate for glioblastoma.
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Antineoplásicos/farmacologia , Antitussígenos/farmacologia , Fenilbutiratos/farmacologia , Animais , Antineoplásicos/química , Antitussígenos/química , Apoptose/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Reposicionamento de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Camundongos , Modelos Moleculares , Fenilbutiratos/química , Ligação Proteica , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Far-infrared (FIR) irradiation is reported to inhibit cell proliferation in various types of cancer cells; the underlying mechanism, however, remains unclear. We explored the molecular mechanisms using MDA-MB-231 human breast cancer cells. FIR irradiation significantly inhibited cell proliferation and colony formation compared to hyperthermal stimulus, with no alteration in cell viability. No increase in DNA fragmentation or phosphorylation of DNA damage kinases including ataxia-telangiectasia mutated kinase, ataxia telangiectasia and Rad3-related kinase, and DNA-dependent protein kinase indicated no DNA damage. FIR irradiation increased the phosphorylation of checkpoint kinase 2 (Chk2) at Thr68 (p-Chk2-Thr68) but not that of checkpoint kinase 1 at Ser345. Increased nuclear p-Chk2-Thr68 and Ca2+/CaM accumulations were found in FIR-irradiated cells, as observed in confocal microscopic analyses and cell fractionation assays. In silico analysis predicted that Chk2 possesses a Ca2+/calmodulin (CaM) binding motif ahead of its kinase domain. Indeed, Chk2 physically interacted with CaM in the presence of Ca2+, with their binding markedly pronounced in FIR-irradiated cells. Pre-treatment with a Ca2+ chelator significantly reversed FIR irradiation-increased p-Chk2-Thr68 expression. In addition, a CaM antagonist or small interfering RNA-mediated knockdown of the CaM gene expression significantly attenuated FIR irradiation-increased p-Chk2-Thr68 expression. Finally, pre-treatment with a potent Chk2 inhibitor significantly reversed both FIR irradiation-stimulated p-Chk2-Thr68 expression and irradiation-repressed cell proliferation. In conclusion, our results demonstrate that FIR irradiation inhibited breast cancer cell proliferation, independently of DNA damage, by activating the Ca2+/CaM/Chk2 signaling pathway in the nucleus. These results demonstrate a novel Chk2 activation mechanism that functions irrespective of DNA damage.
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Cálcio/metabolismo , Calmodulina/metabolismo , Proliferação de Células/efeitos da radiação , Quinase do Ponto de Checagem 2/metabolismo , Dano ao DNA/efeitos da radiação , Raios Infravermelhos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos da radiação , Quinase do Ponto de Checagem 2/antagonistas & inibidores , Quinase do Ponto de Checagem 2/genética , Feminino , Humanos , Fosforilação/efeitos da radiação , Ligação Proteica , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Regulação para Cima/efeitos da radiaçãoRESUMO
INTRODUCTION: Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) mediate renal function during diabetic and non-diabetic nephropathy development. Methylglyoxal-lysine dimer (MOLD), a typical toxic advanced glycation end product (TAGE), contributes to inflammatory responses during renal diseases. This study determines the effect of MOLD on inflammatory responses in mouse mesangial cells. METHODS AND RESULTS: The murine mesangial cell line SV40 MES 13 is used to assess nuclear factor-kappa B (NF-κB) expression, reactive oxygen species (ROS) production, and mitochondria labeling. The interaction model between RAGE and MOLD is also determined. MOLD treatment of mesangial cells markedly increases RAGE expression and the linkage with V-type Ig domain of RAGE. MOLD induces ROS production and mitochondrial dysfunction. MOLD activates phosphatidylinositol 3-kinase-protein kinase B (PI3KB) and NF-κB signaling pathways. It is confirmed that these changes are reversed when ROS is suppressed. These effects may be regulated through mitogen-activated protein kinases and pro-inflammatory cytokines in circulatory inflammation responses. CONCLUSION: MOLD plays a major role in nephropathy via ROS production and mitochondrial dysfunction through direct association with RAGE. Further, the NF-kB and PI3K/AKT signaling pathways triggered by ROS mediate the inflammatory response to exacerbate MOLD-induced damages in inflammation-related diabetic and non-diabetic renal diseases.
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Produtos Finais de Glicação Avançada/efeitos adversos , Inflamação/induzido quimicamente , Células Mesangiais , Animais , Linhagem Celular , Lisina/efeitos adversos , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Aldeído Pirúvico/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
INTRODUCTION: Many current guidelines on optimal target blood pressure (BP) for chronic kidney disease (CKD) patients are largely based on studies in diabetic and hypertensive patients. However, there have been few studies in patients with glomerular diseases. METHODS: We retrospectively studied the longitudinal association between BP and CKD progression in 1,066 biopsy-proven patients diagnosed with primary glomerular diseases, including IgA nephropathy, membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), between 2005 and 2017. The main predictor was time-updated systolic blood pressure (SBP) at every clinic visit. The primary outcome was a composite one including ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from the baseline, and end-stage kidney disease (ESKD). RESULTS: During 5009 person-years of follow-up, the primary outcome occurred in 157 (14.7%) patients. In time-varying Cox model, the adjusted hazard ratios (HRs) (95% confidence interval (CI)) for the primary outcome were 1.48 (0.96-2.29), 2.07 (1.22-3.52), and 2.53 (1.13-5.65) for SBP of 120-129, 130-139, and ≥ 140 mmHg, respectively, compared with SBP < 120 mmHg. This association was particularly evident in patients with elevated proteinuria. However, there was no association between baseline SBP and adverse kidney outcomes. Finally, prediction models failed to show the improvement of predictive performance of SBP compared with that of remission status. Moreover, patients with remission and less controlled SBP had better kidney outcomes than those with non-remission and well-controlled SBP. CONCLUSION: Among patients with glomerular disease, higher time-updated SBP was significantly associated with higher risk of CKD progression. However, the clinical significance of blood pressure was less powerful than remission status.
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Hipertensão , Falência Renal Crônica , Insuficiência Renal Crônica , Pressão Sanguínea , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: This study aims to evaluate the efficacy and effectiveness of a mindfulness-based stress reduction (MBSR) program in improving sleep in cancer survivors. METHODS: Four electronic databases (Cochrane Library, EMBASE, PubMed, and PsycARTICLES) were searched for randomized controlled trials evaluating the effects of MBSR on the sleep of cancer survivors from their inception to May 2020. The primary outcome was sleep quality measured by validated questionnaires such as the Insomnia Severity Index and Pittsburgh Sleep Quality Index. The secondary outcomes were sleep parameters obtained from a sleep diary, polysomnography, and actigraphy. The included studies were critically appraised by the Cochrane risk of bias tool and meta-analyzed. RESULTS: Ten studies were included, and nine studies were analyzed quantitatively. MBSR significantly improved sleep quality compared to usual care (standardized mean difference -0.29, 95 % confidence interval -0.55 to -0.04, I2 = 58 %). However, there were no favorable results with sleep parameters. Compared to active controls, MBSR presented mixed results with sleep quality according to the outcomes and negative results with sleep parameters. CONCLUSION: This review suggests that MBSR helps cancer survivors improve sleep quality. Our results support the possibility of using MBSR for cancer survivors. However, its efficacy and effectiveness in improving sleep quality and sleep parameters are inconclusive because the number of included studies was few with inconsistent results. Further studies with high methodological quality are required to establish conclusive evidence about the efficacy and effectiveness of MBSR in improving sleep quality and sleep parameters in cancer survivors.