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BACKGROUND: Rose myrtle (Rhodomyrtus tomentosa (Ait.) Hassk), is an evergreen shrub species belonging to the family Myrtaceae, which is enriched with bioactive volatiles (α-pinene and ß-caryophyllene) with medicinal and industrial applications. However, the mechanism underlying the volatile accumulation in the rose myrtle is still unclear. RESULTS: Here, we present a chromosome-level genomic assembly of rose myrtle (genome size = 466 Mb, scaffold N50 = 43.7 Mb) with 35,554 protein-coding genes predicted. Through comparative genomic analysis, we found that gene expansion and duplication had a potential contribution to the accumulation of volatile substances. We proposed that the action of positive selection was significantly involved in volatile accumulation. We identified 43 TPS genes in R. tomentosa. Further transcriptomic and TPS gene family analyses demonstrated that the distinct gene subgroups of TPS may contribute greatly to the biosynthesis and accumulation of different volatiles in the Myrtle family of shrubs and trees. The results suggested that the diversity of TPS-a subgroups led to the accumulation of special sesquiterpenes in different plants of the Myrtaceae family. CONCLUSIONS: The high quality chromosome-level rose myrtle genome and the comparative analysis of TPS gene family open new avenues for obtaining a higher commercial value of essential oils in medical plants.
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Cromossomos de Plantas , Evolução Molecular , Genoma de Planta , Genômica , Myrtaceae , Terpenos , Terpenos/metabolismo , Genômica/métodos , Myrtaceae/genética , Myrtaceae/metabolismo , Cromossomos de Plantas/genética , Filogenia , Família MultigênicaRESUMO
BACKGROUND: WD40 proteins, which are highly prevalent in eukaryotes, play important roles in plant development and stress responses. However, systematic identification and exploration of WD40 proteins in tobacco have not yet been conducted. RESULTS: In this study, a total of 399 WD40 regulatory genes were identified in common tobacco (Nicotiana tabacum). Gene structure and motif analysis revealed structural and functional diversity among different clades of tobacco WD40 regulatory genes. The expansion of tobacco WD40 regulatory genes was mainly driven by segmental duplication and purifying selection. A potential regulatory network of NtWD40s suggested that NtWD40s might be regulated by miRNAs and transcription factors in various biological processes. Expression pattern analysis via transcriptome analysis and qRT-PCR revealed that many NtWD40s exhibited tissue-specific expression patterns and might be involved in various biotic and abiotic stresses. Furthermore, we have validated the critical role of NtTTG1, which was located in the nuclei of trichome cells, in enhancing the drought tolerance of tobacco plants. CONCLUSIONS: Our study provides comprehensive information to better understand the evolution of WD40 regulatory genes and their roles in different stress responses in tobacco.
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Resistência à Seca , Nicotiana , Nicotiana/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , FilogeniaRESUMO
BACKGROUND: N6-methyladenosine (m6A) is one of the common internal RNA modifications found in eukaryotes. The m6A modification can regulate various biological processes in organisms through the modulation of alternative splicing, alternative polyadenylation, folding, translation, localization, transport, and decay of multiple types of RNA, without altering the nucleotide sequence. The three components involved in m6A modification, namely writer, eraser, and reader, mediate the abundance of RNA m6A modification through complex collaborative actions. Currently, research on m6A regulatory genes in plants is still in its infancy. RESULTS: In this study, we identified 52 candidate m6A regulatory genes in common tobacco (Nicotiana tabacum L.). Gene structure, conserved domains, and motif analysis showed structural and functional diversity among different subgroups of tobacco m6A regulatory genes. The amplification of m6A regulatory genes were mainly driven by polyploidization and dispersed duplication, and duplicated genes evolved through purified selection. Based on the potential regulatory network and expression pattern analysis of m6A regulatory genes, a significant number of m6A regulatory genes might play important roles in growth, development, and stress response processes. Furthermore, we have confirmed the critical role of NtFIP37B, an m6A writer gene in tobacco, in enhancing drought resistance. CONCLUSIONS: This study provides useful information for better understanding the evolution of m6A regulatory genes and the role of m6A modification in tobacco stress response, and lays the foundation for further elucidating the function of m6A regulatory genes in tobacco.
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Adenosina/análogos & derivados , Resistência à Seca , Nicotiana , Nicotiana/genética , Genes Reguladores , RNA , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , FilogeniaRESUMO
BACKGROUND: Gastric cancer (GC) is a common and aggressive type of cancer worldwide. Despite recent advancements in its treatment, the prognosis for patients with GC remains poor. Understanding the mechanisms of cell death in GC, particularly those related to mitochondrial function, is crucial for its development and progression. However, more research is needed to investigate the significance of the interaction between mitochondrial function and GC cell death. METHODS: We employed a robust computational framework to investigate the role of mitochondria-associated proteins in the progression of GC in a cohort of 1,199 GC patients. Ten machine learning algorithms were utilized and combined into 101 unique combinations. Ultimately, we developed a Mitochondrial-related-Score (MitoScore) using the machine learning model that exhibited the best performance. We observed the upregulation of LEMT2 and further explored its function in tumor progression. Mitochondrial functions were assessed by measuring mitochondrial ATP, mitochondrial membrane potential, and levels of lactate, pyruvate, and glucose. RESULTS: MitoScore showed significant correlations with GC immune and metabolic functions. The higher MitoScore subgroup exhibited enriched metabolic pathways and higher immune activity. Overexpression of LETM2 (leucine zipper and EF-hand containing transmembrane protein 2) significantly enhanced tumor proliferation and metastasis. LETM2 plays a role in promoting GC cell proliferation by activating the mTOR pathway, maintaining mitochondrial homeostasis, and promoting glycolysis. CONCLUSION: The powerful machine learning framework highlights the significant potential of MitoScore in providing valuable insights and accurate assessments for individuals with GC. This study also enhances our understanding of LETM2 as an oncogene signature in GC. LETM2 may promote tumor progression by maintaining mitochondrial health and activating glycolysis, offering potential targets for diagnosis, treatment, and prognosis of GC.
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Aprendizado de Máquina , Mitocôndrias , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Mitocôndrias/metabolismo , Prognóstico , Estudos de Coortes , Masculino , Feminino , Modelos Biológicos , Proliferação de Células , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/metabolismo , MultiômicaRESUMO
Melasma is a common condition of hyperpigmented facial skin. Picosecond lasers are reported to be effective for the treatment of melasma. We aimed to identify the most effective therapeutic mode and elucidate the potential molecular mechanisms of picosecond lasers for the treatment of melasma. Female Kunming mice with melasma-like conditions were treated using four different picosecond laser modes. Concurrently, in vitro experiments were conducted to assess changes in melanin and autophagy in mouse melanoma B16-F10 cells treated with these laser modes. Changes in melanin in mouse skin were detected via Fontana-Masson staining, and melanin particles were evaluated in B16-F10 cells. Real-time polymerase chain reaction and western blotting were used to analyse the expression levels of melanosome and autophagy-related messenger ribonucleic acid (mRNA) and proteins. A combination of large-spot low-fluence 1064-nm and fractional 1064-nm picosecond lasers resulted insignificant decreases in melanin as well as in mRNA and protein expression of melanin-synthesizing enzymes (TYR, TRP-1 and MITF). This combination also led to increased expression of the autophagy-related proteins, Beclin1 and ATG5, with a marked decrease in p62 expression. Intervention with the PI3K activator, 740 Y-P, increased TYR, TRP-1, MITF, p-PI3K, p-AKT, p-mTOR and p62 expression but decreased the expression of LC3, ATG5 and Beclin1. A combination of large-spot low-fluence 1064-nm and fractional 1064-nm picosecond lasers proved more effective and safer. It inhibits melanin production, downregulates the PI3K/AKT/mTOR pathway, enhances melanocyte autophagy and accelerates melanin metabolism, thereby reducing melanin content.
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Autofagia , Melanose , Melanossomas , Transdução de Sinais , Animais , Feminino , Camundongos , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Terapia com Luz de Baixa Intensidade , Melaninas/metabolismo , Melanoma Experimental/metabolismo , Melanoma Experimental/radioterapia , Melanose/metabolismo , Melanossomas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Carbon nanosol (CNS) is a carbon-based nanomaterial capable of promoting plant growth while the underlying mechanism involved in this process remains unknown. This study demonstrates that CNS promotes rice seedling growth under restricted concentrations. Macroelement transporter mutants were investigated to further investigate the CNS-mediated promotion of rice seedling growth. The genetic and physiological findings revealed that nitrate transporter 1.1B (NRT1.1B) and ammonium transporter 1 (AMT1) mutants inhibited the CNS-induced growth development of rice seedlings, whereas potassium transporter (AKT1) and phosphate transporter 8 (PT8) did not exhibit any inhibitory effects. Further investigations demonstrated the inhibition of CNS-mediated growth promotion via glutamine synthetase 1;1 (gs1;1) mutants. Additionally, the administration of CNS resulted in enhanced accumulation of chlorophyll in plants, and the promotion of CNS-induced growth was inhibited by yellow-green leaf 8 (YGL8) mutants and the chlorophyll biosynthetic gene divinyl reductase (DVR) mutants. According to these findings, the CNS promotes plant growth by stimulating chlorophyll biosynthesis. Furthermore, the presence of CNS enhanced the ability of rice to withstand blast, sheath blight (ShB), and bacterial blight. The nrt1.1b, amt1, dvr, and ygl8 mutants did not exhibit a broad spectrum effect. The positive regulation of broad-spectrum resistance in rice by GS1;1 suggests the requirement of N assimilation for CNS-mediated broad-spectrum resistance. In addition, an in vitro assay demonstrated that CNS inhibits the growth of pathogens responsible for blast, ShB, and bacterial blight, namely Magnaporthe oryzae, Rhizoctonia solani AG1-IA, and Xanthomonas oryzae pv. Oryzae, respectively. CNS application may also induce broad-spectrum resistance against bacterial and fungal pathogens, indicating that in addition to its antifungal and antibacterial properties, CNS application may also stimulate N assimilation. Collectively, the results indicate that CNS may be a potential nano-therapeutic agent for improved plant growth promotion while also providing broad-spectrum resistance.
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Carbono , Oryza , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Oryza/efeitos dos fármacos , Oryza/genética , Carbono/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Clorofila/metabolismo , Plântula/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Plântula/microbiologia , Resistência à Doença/efeitos dos fármacosRESUMO
BACKGROUND: Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically evaluate the clinical efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet in treating vascular calcification. METHODS: A comprehensive study search was performed using PubMed, Web of Science, the Cochrane Library, EMBASE and China National Knowledge Internet (CNKI) to collect randomized controlled trials (RCTs) of sodium thiosulfate, bisphosphonates, and cinacalcet for vascular calcification among hemodialysis patients. Then, network meta-analysis was conducted using Stata 17.0 software. RESULTS: In total, eleven RCTs including 1083 patients were qualified for this meta-analysis. We found that cinacalcet (SMD - 0.59; 95% CI [-0.95, -0.24]) had significant benefit on vascular calcification compared with conventional therapy, while sodium thiosulfate or bisphosphonates did not show such efficiency. Furthermore, as for ranking the efficacy assessment, cinacalcet possessed the highest surface under the cumulative ranking curve (SUCRA) value (88.5%) of lessening vascular calcification and was superior to sodium thiosulfate (50.4%) and bisphosphonates (55.4%). Thus, above results suggested that cinacalcet might be the most promising drug for vascular calcification treatment in hemodialysis patients. Mechanistically, our findings illustrated that cinacalcet reduced serum calcium (SMD - 1.20; 95% CI [-2.08, - 0.33]) and showed the tendency in maintaining the balance of intact Parathyroid Hormone (iPTH) level. CONCLUSIONS: This network meta-analysis indicated that cinacalcet appear to be more effective than sodium thiosulfate and bisphosphonates in mitigating vascular calcification through decreasing serum calcium and iPTH. And cinacalcet might be a reasonable option for hemodialysis patients with VC in clinical practice. SYSTEMATIC REVIEW REGISTRATION: [ http://www.crd.york.ac.uk/PROSPERO ], identifier [CRD42022379965].
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Difosfonatos , Tiossulfatos , Calcificação Vascular , Humanos , Difosfonatos/uso terapêutico , Cinacalcete/uso terapêutico , Metanálise em Rede , Cálcio , Calcificação Vascular/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: The objective of this study was to investigate the relationship between vascular calcification, serum lncRNA H19, and Runt-Related Transcription Factor 2 mRNA expression in patients with uremia. Methods: This study is a retrospective study which recruited 146 patients with uremia on dialysis from December 2021 to November 2022. Participants were divided into the VC and non-VC groups based on their chest X-ray calcification ratings. General and clinical data were collected from all patients. Serum H19, Runx2 mRNA, mineral bone disease effectors, and other blood markers were tested. Univariate analysis was performed to compare the changes in each clinical index between these two groups of patients. A multi-factor logistic regression analysis of risk factors for VC was performed. Receiver operating characteristics analyzed the H19 and Runx2 for their diagnostic values for VC. Pearson's test was used to analyze the correlation between the H19 and Runx2 expression and the factors influencing VC. Results: Patients in the VC group had significantly higher creatinine, serum phosphorus, calcium, BMP-2, FGF-23, OPG, and iPTH levels than those in the non-VC group (P < .05), while their albumin levels were significantly lower than those in the non-VC group (P < .05). The expression of H19 and Runx2 mRNA was significantly upregulated in the serum of VC patients (P < .05). H19 was significantly positively correlated with creatinine, serum phosphorus, calcium, BMP-2, OPG, and iPTH (P < .05). Runx2 mRNA was significantly positively correlated with creatinine, FGF-23, and iPTH (P < .05 ), while there was no significant correlation with other factors(P > .05). Albumin, BMP-2, iPTH, H19, and Runx2 were independent correlative-factors of uremic VC. In addition, the combined H19 and Runx2 test (AUC=0.850; 95% CI: 0.781-0.903) had good diagnostic values for the development of VC. Conclusion: Serum H19 and Runx2 levels are significantly associated with VC-related factors and are independent risk factors for uremic VC, and their levels contribute to the diagnosis of uremic VC.
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AIMS: This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m2) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies. METHODS: The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs. RESULTS: A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m2 patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3-5 patients with heart failure (OR: 0.65, 95%CI: 0.54-0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68-0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73-0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60-0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79-2.17) and hypotension (OR:1.57, 95%CI:0.94-2.62) were increased in sacubitril/valsartan group among CKD stages 3-5 patients with heart failure. CONCLUSIONS: Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients.
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Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca , Tetrazóis , Valsartana , Humanos , Aminobutiratos/uso terapêutico , Aminobutiratos/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Tetrazóis/uso terapêutico , Tetrazóis/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Creatinina/sangueRESUMO
Lung cancer is a prevalent and highly lethal disease often complicated by lower respiratory tract infections. Microbial patterns in these infections vary based on treatment modalities. The present study explored the impact of lung cancer treatments on pathogens and clinical characteristics in the presence of lower respiratory tract infections to inform antimicrobial drug selection. A retrospective analysis was performed that included data from 93 patients diagnosed with advanced lung cancer and lower respiratory tract infections between January 2019 and December 2021. Patients were divided into the targeted therapy and chemoradiotherapy groups. Clinical, nutritional, biochemical, infection and pathogenetic indicators were compared. Of the 93 cases, 24 were in the targeted therapy group and 69 were in the chemoradiotherapy group. Pathological type and hospitalization duration differed significantly (P<0.05), but age, sex, smoking history, alcohol consumption and underlying diseases did not (P>0.05). Lymphocyte counts differed (P<0.05), while body mass index, albumin, hemoglobin, alanine aminotransferase and creatinine levels, erythrocyte sedimentation rate, hypersensitive C-reactive protein and procalcitonin levels, and the percentage of neutrophils did not (P>0.05). Pathogenetic testing was negative in 15 patients and positive in 78 patients, with Gram-negative bacteria (61.77%), fungi (17.65%) and viruses (11.76%) predominant in the targeted therapy group. In the chemoradiotherapy group, Gram-negative bacteria (47.46%), fungi (28.81%) and viruses (16.95%) were also more prevalent. Candida albicans was the most frequent fungal infection in both groups, and mixed infections were common (50% in targeted therapy and 73.92% in chemoradiotherapy). The chemoradiotherapy group had significantly more mixed infections (P<0.05). Overall, common pathogens in both groups included Gram-negative bacteria, fungi and viruses. Chemoradiotherapy patients experienced longer hospital stays and a higher incidence of mixed infections, predominantly involving Gram-negative bacteria and fungi. The results provide valuable insights into the rational selection of empirical antibiotics and antifungals for critically ill patients with lung cancer and lower respiratory tract infections in targeted therapy or chemoradiotherapy.
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Ethylene oxide (EO) is a common chemical contaminant in the environment and associated with the occurrence of multiple clinical diseases. This study aimed to explore the association of hemoglobin ethylene oxide (HbEO) levels with the risk of albuminuria in a representative sample of US adults. In total, 3523 participants from National Health and Nutrition Examination Survey (NHANES) 2013-2016 were enrolled and classified into four groups based on HbEO. Restricted cubic spline plots and multiple logistic regression were performed to investigate the connection between HbEO levels and albuminuria, and mediation analysis was applied to elucidate the potential mechanism for the effect of HbEO concentrations on albuminuria. In the results, compared with the extreme quartile of HbEO levels, the weighted prevalence of albuminuria was significantly increased in participants with highest quartile (Q4 vs Q1, 11.2% vs 8.1%). Restricted cubic spline plots revealed that the risk of albuminuria raised non-linearly and positively with elevated HbEO level. After adjusting for confounders, the logistic regression suggested that the risk of albuminuria was enhanced by 12% for each one-unit increase in log-2-transformed HbEO (OR = 1.12, 95% CI, 1.03-1.22, P = 0.007). Moreover, the multivariate ORs (95% CIs) on albuminuria was increased across the increasing HbEO quartiles (Q4 vs Q1, OR = 1.54, 95% CI, 1.09-2.17; P for trend = 0.029). Furthermore, the impact of high HbEO level on albuminuria was partially related to inflammation markers, including white blood cells (17.2%), neutrophils (22.1%), and lymphocytes (19.5%). To sum up, our study identified that high HbEO levels increased the risk of albuminuria in representative population of US adults, and several inflammatory mediators might be potentially involved in EO-associated albuminuria.
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Albuminúria , Óxido de Etileno , Adulto , Humanos , Inquéritos Nutricionais , Albuminúria/epidemiologia , Albuminúria/diagnóstico , Inflamação , HemoglobinasRESUMO
OBJECTIVE: Vascular calcification is a common chronic kidney disease complication. This study aimed to investigate the function of long non-coding RNA (LncRNA) H19 in vascular calcification to explore new therapeutic strategies. METHODS: We induced osteogenic differentiation and calcification of vascular smooth muscle cells (VSMCs) using ß-glycerophosphate. Then, we detected the LncRNA H19 promoter methylation status and Erk1/2 pathways using methylation-specific polymerase chain reaction and western blotting, respectively. RESULTS: Compared with the control group, high phosphorus levels induced VSMC calcification, accompanied by increases in LncRNA H19 and the osteogenic marker Runx2 and reduction of the contractile phenotype marker SM22a. LncRNA H19 knockdown inhibited osteogenic differentiation and calcification of VSMCs. However, the suppressed role of VSMC calcification caused by shRNA H19 was partially reversed by simultaneous activation of the Erk1/2 pathways. Mechanically, we found that the methylation rate of CpG islands in the LncRNA H19 promoter region was significantly lower in the high-phosphorus group, and the hypomethylation state elevated LncRNA H19 levels, which in turn regulated phosphorylated Erk1/2 expression. CONCLUSIONS: LncRNA H19 promoted osteogenic differentiation and calcification of VSMCs by regulating the Erk1/2 pathways. Additionally, hypomethylation of LncRNA H19 promoter CpG islands upregulated LncRNA H19 levels and subsequently activated Erk1/2 phosphorylation.
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RNA Longo não Codificante , Calcificação Vascular , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Músculo Liso Vascular , Osteogênese/genética , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Regiões Promotoras Genéticas , Fósforo , Miócitos de Músculo Liso , Células CultivadasRESUMO
AIM: This study intended to scrutinize the effect of RFR time on adverse renal outcomes and mortality and try to define the cutoff of early RFR. METHODS: We conducted a literature search from database inception to February 2023. Outcome measures incorporated the progression of CKD, delivery of RRT, incidence of composite renal outcomes, and mortality. And pooled results were depicted as odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 11 studies were finally selected (507,989 patients, mean follow-up, 3.89 years). The results exhibited that the crude mortality was lower in patients with early RFR (OR = 0.39, 95% CI: 0.16-0.95, P = 0.037). In addition, patients with early RFR had a lower incidence of progression to CKD (OR = 0.38, 95% CI: 0.17-0.85, P < 0.018), RRT (OR = 0.37, 95% CI: 0.20-0.71, P = 0.03), and composite renal outcomes (OR = 0.18, 95% CI: 0.15-0.20, P < 0.001). CKD progression-related events were significantly higher in patients whose renal function recovered after 7 days (OR = 0.69, 95% CI: 0.47-1.09, P = 0.112) than in those whose renal function recovered within 7 days (OR = 0.23, 95% CI: 0.06-0.92, P = 0.038), and the risk of RRT was lower in patients who recovered within 7 days (OR = 0.32, 95% CI: 0.15-0.66, P = 0.002) than in those who recovered after 7 days (OR = 0.72, 95% CI: 0.17-3.09, P = 0.654) or longer. CONCLUSION: Patients with early RFR had a lower risk of CKD progression, RRT, and composite renal outcomes, as well as lower crude mortality than those without early recovery, despite no marked difference in 30-day, 90-day, and 1-year mortality. We speculated that 7 days may be used as a cutoff for early RFR.
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Injúria Renal Aguda , Recuperação de Função Fisiológica , Humanos , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Rim/fisiopatologia , Fatores de Tempo , Progressão da DoençaRESUMO
BACKGROUND: Striae distensae (SD) is a challenging cosmetic condition. Ablative fractional laser (AFL) is an effective method for treating SD. Recently, fractional radiofrequency (FRF) has been shown to be a promising treatment for SD; however, few studies have shown the differences between FRF and AFL in the treatment of SD. AIMS: This study aimed to evaluate and compare the clinical efficacy and safety of bipolar FRF with 2940-nm erbium yttrium aluminum garnet (Er:YAG) AFL in the treatment of SD. PATIENTS/METHODS: Twenty volunteers with abdominal SD were enrolled in this study. One half of the abdomen was treated with 2940-nm Er:YAG AFL, whereas the other half was treated with bipolar FRF, with three sessions at 4-week intervals. Photographic evaluations of clinical improvement were conducted by two independent investigators before and after treatment, and the patients provided self-assessments. Two participants underwent three punch biopsies, one before treatment and two obtained from bilateral representative skin lesions on the abdomen 3 months following the final treatment. RESULTS: Clinical improvements were observed in SD on both sides of the abdomen after the two treatments. Post-treatment skin biopsies revealed increased thickness in the epidermis and dermis, and higher collagen and elastin density compared to those at the baseline. No statistically significant differences were observed in the clinical outcomes between the two treatment approaches. CONCLUSIONS: The efficacy and safety of bipolar FRF treatment are comparable to those of 2940-nm Er:YAG AFL treatment, providing an alternative and effective treatment for SD.
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Lasers de Estado Sólido , Estrias de Distensão , Humanos , Estrias de Distensão/terapia , Lasers de Estado Sólido/uso terapêutico , Lasers de Estado Sólido/efeitos adversos , Feminino , Adulto , Resultado do Tratamento , Adulto Jovem , Masculino , Abdome , Pele/efeitos da radiação , Pele/patologia , Terapia por Radiofrequência/efeitos adversos , Terapia por Radiofrequência/métodos , Terapia por Radiofrequência/instrumentação , Biópsia/efeitos adversos , Satisfação do PacienteRESUMO
Vascular calcification (VC) is directly related to high mortality in chronic kidney disease (CKD), and cellular apoptosis of vascular smooth muscle cells (VSMCs) is a crucial process in the initiation of VC. Microtubule affinity-regulating kinase 4 (Mark4), known as a serine/threonine protein kinase, can induce cell apoptosis and autophagy by modulating Akt phosphorylation. However, the potential functions and molecular mechanisms of Mark4 in VSMCs apoptosis and calcification need to be further explored. Initially, our data indicated that the mRNA expression of Mark4 was prominently elevated in high phosphorus-stimulated human VSMCs compared with the other members in Marks. Consistently, Mark4 expression was found to be significantly increased in the calcified arteries of both CKD patients and rats. In vitro, silencing Mark4 suppressed apoptosis-specific marker expression by promoting Akt phosphorylation, finally attenuating VSMCs calcification induced by high phosphate. Mechanically, the transcription factor Sp1 was enriched in the Mark4 promoter region and modulated Mark4 transcription. Moreover, SET domain-containing protein 8 (Setd8) was proved to interact with Sp1 and jointly participated in the transcriptional regulation of Mark4. Finally, rescue experiments revealed that Setd8 contributed to VSMCs apoptosis and calcification by modulating Mark4 expression. In conclusion, these findings reveal that Mark4 is transcriptionally activated by Sp1, which is interacted with Setd8, to promote VSMCs calcification through Akt-mediated antiapoptotic effects, suggesting that Mark4 represents a potent and promising therapeutic target for VC in CKD.
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Insuficiência Renal Crônica , Calcificação Vascular , Animais , Humanos , Ratos , Apoptose/genética , Células Cultivadas , Microtúbulos/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Calcificação Vascular/metabolismoRESUMO
Background: Vascular calcification (VC) commonly occurs and seriously increases the risk of cardiovascular events and mortality in patients with hemodialysis. For optimizing individual management, we will develop a diagnostic multivariable prediction model for evaluating the probability of VC. Methods: The study was conducted in four steps. First, identification of miRNAs regulating osteogenic differentiation of vascular smooth muscle cells (VSMCs) in calcified condition. Second, observing the role of miR-129-3p on VC in vitro and the association between circulating miR-129-3p and VC in hemodialysis patients. Third, collecting all indicators related to VC as candidate variables, screening predictors from the candidate variables by Lasso regression, developing the prediction model by logistic regression and showing it as a nomogram in training cohort. Last, verifying predictive performance of the model in validation cohort. Results: In cell experiments, miR-129-3p was found to attenuate vascular calcification, and in human, serum miR-129-3p exhibited a negative correlation with vascular calcification, suggesting that miR-129-3p could be one of the candidate predictor variables. Regression analysis demonstrated that miR-129-3p, age, dialysis duration and smoking were valid factors to establish the prediction model and nomogram for VC. The area under receiver operating characteristic curve of the model was 0.8698. The calibration curve showed that predicted probability of the model was in good agreement with actual probability and decision curve analysis indicated better net benefit of the model. Furthermore, internal validation through bootstrap process and external validation by another independent cohort confirmed the stability of the model. Conclusion: We build a diagnostic prediction model and present it as an intuitive tool based on miR-129-3p and clinical indicators to evaluate the probability of VC in hemodialysis patients, facilitating risk stratification and effective decision, which may be of great importance for reducing the risk of serious cardiovascular events.
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OBJECTIVE: To study the etiological characteristics of community-acquired pneumonia (CAP) combined with type 2 diabetes (T2D), providing a reference for early clinical diagnosis and treatment of the disease. METHODS: We selected a total of 93 patients with CAP and analyzed their metagenomics nextgeneration sequencing (mNGS) data. The case group comprised 46 patients with combined CAP/T2D, and the control group comprised 47 patients without diabetes. We analyzed the pathogenic findings of the two groups. RESULTS: There were statistically significant differences in age between the two groups (P = 0.001). Leukocytes (P = 0.012), blood platelets (P = 0.034), fibrinogen (P = 0.037), D-dimer (P = 0.000), calcitonin ogen (P = 0.015), ultrasensitive C-reactive protein or C-reactive protein (CRP) (P = 0.000), serum amyloid A (P = 0.000), and erythrocyte sedimentation rate (P = 0.003) were higher in the case group than in the control group. Albumin was lower in the case group than in the control group. All differences were statistically significant. The infection rates of Klebsiella pneumoniae (P = 0.030), Pseudomonas aeruginosa (P = 0.043), and Candida albicans (P = 0.032) were significantly different between the two groups. CONCLUSION: Compared with those without diabetes, the infection rates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were higher in patients with combined CAP/T2D.
Assuntos
Infecções Comunitárias Adquiridas , Diabetes Mellitus Tipo 2 , Diagnóstico Precoce , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/epidemiologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Pneumonia/diagnóstico , Pneumonia/sangue , Pneumonia/microbiologia , Estudos de Casos e Controles , Metagenômica/métodos , Adulto , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/epidemiologiaRESUMO
BACKGROUND: Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. METHODS: We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan-Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. RESULTS: The TSR cutoff was identified to be - 6.6%. Median PFS and OS were longer in the group with a TSR < -6.6% than in the group with a TSR ≥ - 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < - 6.6% than when it was > - 6.6%. Brain metastasis-free survival was better in the group with a TSR < - 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS. CONCLUSIONS: The TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Masculino , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Idoso , Prognóstico , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , RadiômicaRESUMO
ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m 6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). Conclusion: After successfully establishing a vascular parkinsonism rabbit model, m 6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques.