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Adipogenesis is a process that differentiates new adipocytes from precursor cells and is tightly regulated by several factors, including many transcription factors and various post-translational modifications. Recently, new roles of adipogenesis have been suggested in various diseases. However, the molecular mechanisms and functional modulation of these adipogenic genes remain poorly understood. This review summarizes the regulatory factors and modulators of adipogenesis and discusses future research directions to identify novel mechanisms regulating adipogenesis and the effects of adipogenic regulators in pathological conditions. The master adipogenic transcriptional factors PPARγ and C/EBPα were identified along with other crucial regulatory factors such as SREBP, Kroxs, STAT5, Wnt, FOXO1, SWI/SNF, KLFs, and PARPs. These transcriptional factors regulate adipogenesis through specific mechanisms, depending on the adipogenic stage. However, further studies related to the in vivo role of newly discovered adipogenic regulators and their function in various diseases are needed to develop new potent therapeutic strategies for metabolic diseases and cancer.
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Adipocitos , Adipogénesis , Adipogénesis/fisiología , Humanos , Animales , Adipocitos/metabolismo , PPAR gamma/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión GénicaRESUMEN
Population aging has increased the global prevalence of aging-related diseases, including cancer, sarcopenia, neurological disease, arthritis, and heart disease. Understanding aging, a fundamental biological process, has led to breakthroughs in several fields. Cellular senescence, evinced by flattened cell bodies, vacuole formation, and cytoplasmic granules, ubiquitously plays crucial roles in tissue remodeling, embryogenesis, and wound repair as well as in cancer therapy and aging. The lack of universal biomarkers for detecting and quantifying senescent cells, in vitro and in vivo, constitutes a major limitation. The applications and limitations of major senescence biomarkers, including senescence-associated ß-galactosidase staining, telomere shortening, cell-cycle arrest, DNA methylation, and senescence-associated secreted phenotypes are discussed. Furthermore, explore senotherapeutic approaches for aging-associated diseases and cancer. In addition to the conventional biomarkers, this review highlighted the in vitro, in vivo, and disease models used for aging studies. Further, technologies from the current decade including multi-omics and computational methods used in the fields of senescence and aging are also discussed in this review. Understanding aging-associated biological processes by using cellular senescence biomarkers can enable therapeutic innovation and interventions to improve the quality of life of older adults.
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Textile wastewater accounts for a significant proportion of industrial wastewater worldwide. In particular, dye wastewater accounts for a large proportion and consists of non-degradable dyes, which are substances resistant to biodegradation. Methylene blue is a representative example of such non-degradable dyes. It is not biologically degraded and exhibits toxicity. Various methods for their decomposition are currently being studied. Advanced oxidation processes (AOPs), which generate highly reactive hydroxyl radicals that oxidize and degrade pollutants, have been actively studied. Particularly, the photocatalytic degradation method using TiO2 nanoparticles is one of the most actively studied fields; however, there are still concerns regarding the toxicity of nanoparticles. Research is currently being conducted on AOPs using the cavitation phenomenon of ultrasonic waves. However, achieving high efficiency using existing ultrasonic equipment is difficult. Therefore, in this study, we evaluated a new water treatment technology through AOPs using a focused ultrasonic system with a cylindrical piezoelectric ceramic structure. After determining the optimal conditions for degradation, the degradation process was evaluated as a useful tool for mitigating the toxicity of methylene blue. We found that, under the optimal conditions of 100 W intensity at a frequency of 400 kHz, this system is a helpful instrument for degradation and a new water treatment technology suitable for removing ecotoxicity and genotoxicity.
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The growing interest in microalgae and cyanobacteria biomass as an alternative to traditional animal feed is hindered by high production costs. Using wastewater (WW) as a cultivation medium could offer a solution, but this approach risks introducing harmful substances into the biomass, leading to significant safety concerns. In this study, we addressed these challenges by selectively extracting nitrates and phosphates from WW using drinking water treatment residuals (DWTR) and chitosan. This method achieved peak adsorption capacities of 4.4 mg/g for nitrate and 6.1 mg/g for phosphate with a 2.5 wt% chitosan blend combined with DWTR-nitrogen. Subsequently, these extracted nutrients were employed to cultivate Spirulina platensis, yielding a biomass productivity rate of 0.15 g/L/d, which is comparable to rates achieved with commercial nutrients. By substituting commercial nutrients with nitrate and phosphate from WW, we can achieve a 18 % reduction in the culture medium cost. While the cultivated biomass was initially nitrogen-deficient due to low nitrate levels, it proved to be protein-rich, accounting for 50 % of its dry weight, and contained a high concentration of free amino acids (1260 mg/g), encompassing all essential amino acids. Both in vitro and in vivo toxicity tests affirmed the biomass's safety for use as an animal feed component. Future research should aim to enhance the economic feasibility of this alternative feed source by developing efficient adsorbents, utilizing cost-effective reagents, and implementing nutrient reuse strategies in spent mediums.
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Cancer-associated cachexia (CAC) is a multifactorial disorder characterized by an unrestricted loss of body weight as a result of muscle and adipose tissue atrophy. Cachexia is influenced by several factors, including decreased metabolic activity and food intake, an imbalance between energy uptake and expenditure, excessive catabolism, and inflammation. Cachexia is highly associated with all types of cancers responsible for more than half of cancer-related mortalities worldwide. In healthy individuals, adipose tissue significantly regulates energy balance and glucose homeostasis. However, in metastatic cancer patients, CAC occurs mainly because of an imbalance between muscle protein synthesis and degradation which are organized by certain extracellular ligands and associated signaling pathways. Under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1α) accumulated and translocated to the nucleus and activate numerous genes involved in cell survival, invasion, angiogenesis, metastasis, metabolic reprogramming, and cancer stemness. On the other hand, the ubiquitination proteasome pathway is inhibited during low O2 levels which promote muscle wasting in cancer patients. Therefore, understanding the mechanism of the HIF-1 pathway and its metabolic adaptation to biomolecules is important for developing a novel therapeutic method for cancer and cachexia therapy. Even though many HIF inhibitors are already in a clinical trial, their mechanism of action remains unknown. With this background, this review summarizes the basic concepts of cachexia, the role of inflammatory cytokines, pathways connected with cachexia with special reference to the HIF-1 pathway and its regulation, metabolic changes, and inhibitors of HIFs.
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Caquexia , Neoplasias , Humanos , Caquexia/patología , Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias/complicaciones , Neoplasias/metabolismo , Tejido Adiposo/metabolismo , Hipoxia/metabolismoRESUMEN
The roots of Paeonia lactiflora Pall., (Paeoniae Radix, PL) are a well-known herbal remedy used to treat fever, rheumatoid arthritis, systemic lupus erythematosus, hepatitis, and gynecological disorders in East Asia. Here we evaluated the genetic toxicity of PL extracts (as a powder [PL-P] and hot-water extract [PL-W]) in accordance with the Organization for Economic Co-operation and Development guidelines. The Ames test revealed that PL-W was not toxic to S. typhimurium strains and E. coli in absence and presence of the S9 metabolic activation system at concentrations up to 5000 µg/plate, but PL-P produced a mutagenic response to TA100 in the absence of S9 mix. PL-P was cytotoxic in in vitro chromosomal aberrations (more than a 50 % decrease in cell population doubling time), and it increased the frequency of structural and numerical aberrations in absence and presence of S9 mix in a concentration-dependent manner. PL-W was cytotoxic in the in vitro chromosomal aberration tests (more than a 50 % decrease in cell population doubling time) only in the absence of S9 mix, and it induced structural aberrations only in the presence of S9 mix. PL-P and PL-W did not produce toxic response during the in vivo micronucleus test after oral administration to ICR mice and did not induce positive results in the in vivo Pig-a gene mutation and comet assays after oral administration to SD rats. Although PL-P showed genotoxic in two in vitro tests, the results from physiologically relevant in vivo Pig-a gene mutation and comet assays illustrated that PL-P and PL-W does not cause genotoxic effects in rodents.
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Aberraciones Cromosómicas , Paeonia , Extractos Vegetales , Animales , Ratones , Ratas , Daño del ADN , Escherichia coli , Ratones Endogámicos ICR , Paeonia/toxicidad , Ratas Sprague-Dawley , Extractos Vegetales/toxicidad , Raíces de Plantas/toxicidad , Salmonella typhimuriumRESUMEN
CRISPR/Cas9-based transcriptional regulation systems can induce the site-specific activation or repression of endogenous genes. p300 is a transcriptional co-activator that functions as a histone acetyltransferase that regulates gene transcription via chromatin remodeling. Here, we generated a human embryonic stem cell line stably expressing catalytically dead Cas9 (dCas9) fused to the catalytic core domain of human p300 via lentiviral transduction. This cell line can be used for locus-specific histone acetylation in combination with guide RNAs, and is a valuable tool for gene regulation in stem cell research.
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Proteína 9 Asociada a CRISPR , Células Madre Embrionarias Humanas , Humanos , Proteína 9 Asociada a CRISPR/genética , Sistemas CRISPR-Cas/genética , Regulación de la Expresión Génica , Factores de Transcripción/genética , Línea Celular , Activación TranscripcionalRESUMEN
Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.
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Neoplasias , Plantas Medicinales , Humanos , Pronóstico , Caquexia/etiología , Caquexia/genética , Simulación del Acoplamiento Molecular , Farmacología en Red , Perfilación de la Expresión Génica , Extractos Vegetales , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/genéticaRESUMEN
Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, anticancer, antiaging, and anti-diabetes effects. It is widely used in traditional medicine to treat liver and kidney diseases; however, the protective effect of ACSE on sepsis and its mechanisms are unknown. In the present study, we investigated the anti-inflammatory effects and potential mechanisms of the action of ACSE on sepsis. We show that ACSE improved survival rates in mouse models of acute sepsis induced by CLP (cecal ligation and puncture) and LPS stimulation. ACSE administration decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in sepsis-induced mice. Furthermore, ACSE reduced the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the serum of septic mice. ACSE treatment inhibited the expression of these proinflammatory genes in LPS-stimulated J774 macrophages. Moreover, ACSE inhibited the phosphorylation of the IκB kinase (IKK) and the nuclear translocation of p65 NF-κB by LPS stimulation in macrophages. These results reveal the mechanism underlying the protective effect of ACSE against sepsis by inhibiting NF-κB activation and suggest that ACSE could be a potential therapeutic candidate to treat acute inflammatory diseases.
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Planta del Astrágalo , Sepsis , Choque Séptico , Animales , Ratones , Lipopolisacáridos/toxicidad , FN-kappa B , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Etanol , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
Sepsis is a systemic inflammatory disease to infections and results in tissue damage and multiple organ failure. Ponciri Fructus Immaturus (PFI) is widely used in traditional medicine for allergic inflammation and gastrointestinal disorders. However, the effect of PFI on sepsis is still unknown. This study investigated the anti-inflammatory and antiseptic effects of PFI ethanol extract (PFIE) in LPS-stimulated J774 macrophages and mice with CLP- or LPS-induced sepsis, respectively. PFIE attenuates the LPS-induced production of the proinflammatory mediator NO by inhibiting the expression of iNOS in J774 cells. Real-time RT-PCR data and ELISA showed that the mRNA and protein levels of TNF-α, IL-1ß, and IL-6 increased in LPS-stimulated J774 cells. However, this induction was significantly suppressed in PFIE pre-treated J774 cells. We also found that PFIE administration increased the survival rate of mice with LPS- and CLP-induced sepsis. Decreased serum levels of AST, ALT, and CK were observed after administration of PFIE, which was associated with reduced production of proinflammatory factors, such as NO, TNF-α, IL-1ß, and IL-6. Moreover, PFIE suppressed the phosphorylation and nuclear translocation of STAT1 in LPS-stimulated J774 cells, suggesting that PFIE can inhibit LPS- and CLP-induced septic shock by suppressing the STAT1 activation. These findings provide the potential therapeutic relevance of PFIE in treating acute inflammatory disease.
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Poly ADP-ribosylation (PARylation) is a post-translational modification process. Following the discovery of PARP-1, numerous studies have demonstrated the role of PARylation in the DNA damage and repair responses for cellular stress and DNA damage. Originally, studies on PARylation were confined to PARP-1 activation in the DNA repair pathway. However, the interplay between PARylation and DNA repair suggests that PARylation is important for the efficiency and accuracy of DNA repair. PARylation has contradicting roles; however, recent evidence implicates its importance in inflammation, metabolism, and cell death. These differences might be dependent on specific cellular conditions or experimental models used, and suggest that PARylation may play two opposing roles in cellular homeostasis. Understanding the role of PARylation in cellular function is not only important for identifying novel therapeutic approaches; it is also essential for gaining insight into the mechanisms of unexplored diseases. In this review, we discuss recent reports on the role of PARylation in mediating diverse cellular functions and homeostasis, such as DNA repair, inflammation, metabolism, and cell death.
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Poli ADP Ribosilación , Poli(ADP-Ribosa) Polimerasas , Reparación del ADN , Humanos , Inflamación , Poli ADP Ribosilación/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismoRESUMEN
The non-POU domain-containing octamer-binding protein (NONO, also referred to as p54nrb) is a multifunctional nuclear protein engaging in transcriptional regulation, mRNA splicing, nuclear retention of defective RNA, and DNA repair. Emerging evidence has demonstrated that p54nrb is subjected to various posttranslational modifications, including phosphorylation and methylation, which may be important regulators of its multifunction. However, among these modifications, direct evidence of p54nrb acetylation and its underlying mechanism remains unclear. In this study, we reported that lysine 371 of p54nrb was reversibly acetylated by the acetyltransferase general control non-depressible 5 (GCN5) and deacetylase sirtuin 1 (SIRT1), which was crucial for activity of p54nrb to inhibit interleukin-8 (IL-8) expression. Mechanistically, GCN5-mediated acetylation attenuates the recruitment of p54nrb on its core binding motif within the IL-8 gene promoter, preferentially increasing the expression of the IL-8 gene. In contrast, deacetylation by SIRT1 reverses this process. Altogether, our data suggest that reversible acetylation is an important switch for the multiple nuclear functions of p54nrb/NONO.
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Proteínas Asociadas a Matriz Nuclear , Factores de Transcripción de Octámeros , Acetilación , Proteínas de Unión al ADN/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Proteínas Asociadas a Matriz Nuclear/genética , Proteínas Asociadas a Matriz Nuclear/metabolismo , Factores de Transcripción de Octámeros/genética , Factores de Transcripción de Octámeros/metabolismo , Procesamiento Proteico-Postraduccional , Proteínas de Unión al ARN/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Even though scars are major issues for patients who undergo facial lacerations, programs for their prevention and early management are not well established. The purpose of this study was to evaluate the clinical outcomes of prophylactic scar assessments and early scar interventions in patients with lacerations. PATIENTS AND METHODS: A total of 116 patients underwent suture line and scar prevention treatment in the emergency room from 2014 to 2015. In the retrospective study, 46 patients who met all the criteria were included in the study. They were assigned to one of the following two scar prevention programs: the standard scar program for prevention, which included taping, silicone sheets, and ointments, and the multimodality scar program for treatment, which included triamcinolone, botulinum toxins, or CO2 fractional lasers. The patterns of early scar program were investigated for the standard scar prevention program and the multimodality scar management program, and we evaluated the scar assessment scores of the patients at 3 and 6 months. RESULTS: Scar scores for the patients who received multimodality scar management showed statistically significant improvements in Patient Scar Assessment (PSA) scales, Stony Brook Scar Evaluation Scales (SBSES), Vancouver Scar Scale (VSS) scores, and Visual Analog Scar (VAS) scales (the p values were 0.008, 0.007, 0.017, and 0.01, respectively). CONCLUSION: The multimodality scar program is more effective for scar prevention than the standard scar program. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Cicatriz , Herida Quirúrgica , Cicatriz/prevención & control , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Lactobacillus curvatus WiKim 38 (LCW), isolated from kimchi, has shown novel immunomodulatory and anti-inflammatory properties. In the present study, to obtain data on the safety of LCW, we performed three genotoxicity (bacterial reverse mutation, chromosome aberration, and micronucleus) and two general toxicity (single-dosing and 13-week repeated-dosing) studies. In the genotoxicity assessment, LCW showed no increased reverse mutation for 4 strains of Salmonella typhimurium and a strain of Escherichia coli. In addition, LCW did not induce chromosome aberrations at concentrations up to 5000 µg/mL in cultured Chinese hamster lung (CHL) cells and did not induce an increased frequency of micronuclei in the bone marrow cells of rats at concentrations up to 2000 mg/kg. In the acute toxicity study using Sprague-Dawley (SD) rats, the approximate lethal dose of LCW was determined to be over 5000 mg/kg body weight (b.w.) in both sexes. Finally, in the subchronic toxicity study, no LCW-related adverse effects were observed at concentrations up to 5000 mg/kg b.w./day. Consequently, LCW is considered not to have mutagenic effects, and its no-observed-adverse-effect-level (NOAEL) is 5000 mg/kg b.w., equivalent to approximately 4.71 × 109 CFU/kg b.w., suggesting the LCW could be a potential probiotic for humans based on its safety profile.
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Lactobacillus/patogenicidad , Probióticos/toxicidad , Animales , Células de la Médula Ósea/metabolismo , Cromosomas/metabolismo , Escherichia coli/genética , Femenino , Masculino , Pruebas de Micronúcleos , Nivel sin Efectos Adversos Observados , Ratas Sprague-Dawley , Salmonella typhimurium/genética , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad SubcrónicaRESUMEN
OBJECTIVE: Data on ventricular-arterial coupling using invasive hemodynamic studies are limited. This study was performed to clarify the interaction between aortic pressures and left ventricular end-diastolic pressure (LVEDP) using invasive catheterization. PATIENTS AND METHODS: A total of 104 consecutive stable patients (mean age, 65.8 ± 10.0 years; 56% men) undergoing invasive coronary angiography (ICA) were prospectively evaluated. LVEDP and central aortic pressures [systolic blood pressure (aSBP) and diastolic blood pressure (aDBP)] were sequentially measured using a pigtail catheter before ICA. Aortic pulse pressure (aPP) was defined by the difference between aSBP and aDBP. RESULTS: A total of 82 patients (79%) had obstructive coronary artery disease (≥50% stenosis). The mean LVEDP value was 18.7 ± 6.4 mmHg. Univariable analyses showed that aSBP (r = 0.309, P = 0.001) and aPP (r = 0.286, P = 0.003) significantly correlated with LVEDP, whereas aDBP was not correlated with LVEDP (P > 0.05). Multivariable analysis revealed that aSBP (ß = 0.345, P = 0.001) and aPP (ß = 0.276, P = 0.018) remained independent predictors of LVEDP even after controlling for potential confounders. CONCLUSION: Invasively measured aSBP and aPP were independently associated with invasively measured LVEDP in patients undergoing ICA. This result provides additional evidence of a close interaction between central aortic pressure and LV diastolic function in this population.
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Aorta/fisiopatología , Presión Arterial , Determinación de la Presión Sanguínea/métodos , Cateterismo Cardíaco , Angiografía Coronaria , Función Ventricular Izquierda , Anciano , Diástole , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Manganese superoxide dismutase (MnSOD) functions as a tumor suppressor; however, once tumorigenesis occurs, clinical data suggest MnSOD levels correlate with more aggressive human tumors, implying a potential dual function of MnSOD in the regulation of metabolism. Here we show, using in vitro transformation and xenograft growth assays that the MnSOD-K68 acetylation (Ac) mimic mutant (MnSODK68Q) functions as a tumor promoter. Interestingly, in various breast cancer and primary cell types the expression of MnSODK68Q is accompanied with a change of MnSOD's stoichiometry from a known homotetramer complex to a monomeric form. Biochemical experiments using the MnSOD-K68Q Ac-mimic, or physically K68-Ac (MnSOD-K68-Ac), suggest that these monomers function as a peroxidase, distinct from the established MnSOD superoxide dismutase activity. MnSODK68Q expressing cells exhibit resistance to tamoxifen (Tam) and cells selected for Tam resistance exhibited increased K68-Ac and monomeric MnSOD. These results suggest a MnSOD-K68-Ac metabolic pathway for Tam resistance, carcinogenesis and tumor progression.
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Neoplasias de la Mama/genética , Carcinogénesis/genética , Resistencia a Antineoplásicos/genética , Superóxido Dismutasa/genética , Acetilación , Animales , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Humanos , Técnicas In Vitro , Lisina/metabolismo , Células MCF-7 , Ratones , Mutación , Trasplante de Neoplasias , Peroxidasa/metabolismo , Estructura Cuaternaria de Proteína/genética , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Tamoxifeno/uso terapéutico , Proteínas Supresoras de TumorRESUMEN
The distal forearm is the preferred site for hemodialysis access. However, forearm vessels have small diameter, which may lead to complications of arteriovenous fistulas constructed at this site. Indeed, the mean patency rate of such fistulas has been reported at 65.2% (range, 56-79%) at 1 year postoperatively. In this study, we aimed to evaluate the patency rate of Brescia-Cimino arteriovenous fistulas constructed under microscopic guidance. We retrospectively evaluated the records of patients with chronic renal failure who received a Brescia-Cimino arteriovenous fistula between 2014 and 2015 for hemodialysis access. Preoperative venography and Doppler mapping were used to evaluate vein diameter at the wrist. Veins with a diameter of >2âmm were chosen. End-to-side microanastomosis was performed using Nylon #9-0 suture under microscopic guidance. Postoperatively, monthly follow-up (first with venography; with Doppler ultrasound thereafter) was conducted to detect vessel obstruction and evaluate blood flow. Six of the seven patients included in this study received hemodialysis without signs of obstruction or complications. On Kaplan-Meier survival analysis, the mean patency rate at 2 years postoperatively was 85.7%. One patient (female, 60 years) had vessel obstruction and underwent percutaneous transluminal angioplasty 3 times after receiving the arteriovenous fistula. The median follow-up duration was 41 months (range, 25-47 months). Our experience indicates that, for relatively healthy vessels with a diameter of >2âmm, Brescia-Cimino arteriovenous fistulas at the wrist can be safely constructed using microsurgical suturing under microscopic guidance, without complications such as ischemic hand syndrome or infection.
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Derivación Arteriovenosa Quirúrgica/métodos , Fallo Renal Crónico/terapia , Microcirugia/métodos , Diálisis Renal , Técnicas de Sutura , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Retrospectivos , Resultado del Tratamiento , Muñeca/irrigación sanguínea , Muñeca/cirugíaRESUMEN
PURPOSE: This study aimed to compare the efficacy and safety of generic and branded irbesartan for 8 weeks in patients with mild-to-moderate essential hypertension. PATIENTS AND METHODS: We screened 221 patients with mild-to-moderate hypertension. After exclusion per study criteria, 177 subjects were randomized to receive 150 mg generic irbesartan (n=91) or branded irbesartan (n=86) as the intention to treat set. The primary efficacy endpoint of this study was the change in mean sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks between the generic and branded irbesartan groups. The secondary efficacy endpoints were the change in mean SiDBP at Week 4 from baseline and the change in mean sitting systolic blood pressure (SiSBP) at Weeks 4 and 8 from baseline in both groups. All safety issues were evaluated. RESULTS: At Week 8, the generic and branded irbesartan groups showed significantly reduced SiDBP (-10.3±8.0, -10.7±7.7 mmHg, all P<0.0001) compared with baseline values, and the mean between-group difference in SiDBP change after 8 weeks of treatment was -0.4±1.2 mmHg, showing the non-inferiority of generic irbesartan vs branded irbesartan. Furthermore, secondary efficacy, which was the mean change of SiDBP from baseline at 4 weeks, was comparable between the two groups (-9.4±8.1 vs -9.9±7.4 mmHg, P=0.69). There were no between-group differences in mean changes of SiSBP after 4 or 8 weeks of treatment (P=0.78, P=0.97, respectively), or in the incidence of adverse effects (16.7 vs 24.4%, P=0.20). CONCLUSION: Generic irbesartan treatment in patients with mild-to-moderate essential hypertension has shown effective antihypertensive effects comparable with the branded irbesartan treatment, with similar incidence of adverse effects.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Medicamentos Genéricos/uso terapéutico , Hipertensión/tratamiento farmacológico , Irbesartán/uso terapéutico , Adulto , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Antihipertensivos/efectos adversos , Medicamentos Genéricos/efectos adversos , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Irbesartán/efectos adversos , Masculino , Persona de Mediana Edad , República de Corea , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Mice lacking Sirt2 spontaneously develop tumors in multiple organs, as well as when expressed in combination with oncogenic KrasG12D, leading to pancreatic tumors. Here, we report that after caerulein-induced pancreatitis, Sirt2-deficient mice exhibited an increased inflammatory phenotype and delayed pancreatic tissue recovery. Seven days post injury, the pancreas of Sirt2-/- mice display active inflammation, whereas wild-type mice had mostly recovered. In addition, the pancreas from the Sirt2-/- mice exhibited extensive tissue fibrosis, which was still present at six weeks after exposure. The mice lacking Sirt2 also demonstrated an enhanced whole body pro-inflammatory phenotype that was most obvious with increasing age. Importantly, an accumulation of a cell population with spontaneous cancerous KrasG12D mutations was observed in the Sirt2-/- mice that is enhanced in the recovering pancreas after exposure to caerulein. Finally, transcriptome analysis of the pancreas of the Sirt2-/- mice exhibited a pro-inflammatory genomic signature. These results suggest that loss of Sirt2, as well as increased age, enhanced the immune response to pancreatic injury and induced an inflammatory phenotype permissive for the accumulation of cells carrying oncogenic Kras mutations.