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1.
Cell ; 187(17): 4605-4620.e17, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-38959891

RESUMO

The ability of mitochondria to coordinate stress responses across tissues is critical for health. In C. elegans, neurons experiencing mitochondrial stress elicit an inter-tissue signaling pathway through the release of mitokine signals, such as serotonin or the Wnt ligand EGL-20, which activate the mitochondrial unfolded protein response (UPRMT) in the periphery to promote organismal health and lifespan. We find that germline mitochondria play a surprising role in neuron-to-periphery UPRMT signaling. Specifically, we find that germline mitochondria signal downstream of neuronal mitokines, Wnt and serotonin, and upstream of lipid metabolic pathways in the periphery to regulate UPRMT activation. We also find that the germline tissue itself is essential for UPRMT signaling. We propose that the germline has a central signaling role in coordinating mitochondrial stress responses across tissues, and germline mitochondria play a defining role in this coordination because of their inherent roles in germline integrity and inter-tissue signaling.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Células Germinativas , Mitocôndrias , Transdução de Sinais , Resposta a Proteínas não Dobradas , Animais , Caenorhabditis elegans/metabolismo , Mitocôndrias/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Células Germinativas/metabolismo , Neurônios/metabolismo , Serotonina/metabolismo , Proteínas Wnt/metabolismo
2.
Cell ; 187(16): 4289-4304.e26, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38942015

RESUMO

Cellular homeostasis is intricately influenced by stimuli from the microenvironment, including signaling molecules, metabolites, and pathogens. Functioning as a signaling hub within the cell, mitochondria integrate information from various intracellular compartments to regulate cellular signaling and metabolism. Multiple studies have shown that mitochondria may respond to various extracellular signaling events. However, it is less clear how changes in the extracellular matrix (ECM) can impact mitochondrial homeostasis to regulate animal physiology. We find that ECM remodeling alters mitochondrial homeostasis in an evolutionarily conserved manner. Mechanistically, ECM remodeling triggers a TGF-ß response to induce mitochondrial fission and the unfolded protein response of the mitochondria (UPRMT). At the organismal level, ECM remodeling promotes defense of animals against pathogens through enhanced mitochondrial stress responses. We postulate that this ECM-mitochondria crosstalk represents an ancient immune pathway, which detects infection- or mechanical-stress-induced ECM damage, thereby initiating adaptive mitochondria-based immune and metabolic responses.


Assuntos
Matriz Extracelular , Homeostase , Mitocôndrias , Resposta a Proteínas não Dobradas , Matriz Extracelular/metabolismo , Animais , Mitocôndrias/metabolismo , Humanos , Fator de Crescimento Transformador beta/metabolismo , Dinâmica Mitocondrial , Camundongos , Transdução de Sinais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/imunologia
3.
Annu Rev Cell Dev Biol ; 38: 179-218, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-35804477

RESUMO

Mitochondria are traditionally known as the powerhouse of the cell, but their functions extend far beyond energy production. They are vital in cellular and organismal pathways that direct metabolism, stress responses, immunity, and cellular fate. To accomplish these tasks, mitochondria have established networks of both intra- and extracellular communication. Intracellularly, these communication routes comprise direct contacts between mitochondria and other subcellular components as well as indirect vesicle transport of ions, metabolites, and other intracellular messengers. Extracellularly, mitochondria can induce stress responses or other cellular changes that secrete mitochondrial cytokine (mitokine) factors that can travel between tissues as well as respond to immune challenges from extracellular sources. Here we provide a current perspective on the major routes of communication for mitochondrial signaling, including their mechanisms and physiological impact. We also review the major diseases and age-related disorders associated with defects in these signaling pathways. An understanding of how mitochondrial signaling controls cellular homeostasis will bring greater insight into how dysfunctional mitochondria affect health in disease and aging.


Assuntos
Mitocôndrias , Transdução de Sinais , Citocinas/metabolismo , Homeostase , Mitocôndrias/metabolismo
4.
Mol Cell ; 76(1): 110-125.e9, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31474573

RESUMO

Failure to make adaptive immune responses is a hallmark of aging. Reduced B cell function leads to poor vaccination efficacy and a high prevalence of infections in the elderly. Here we show that reduced autophagy is a central molecular mechanism underlying immune senescence. Autophagy levels are specifically reduced in mature lymphocytes, leading to compromised memory B cell responses in old individuals. Spermidine, an endogenous polyamine metabolite, induces autophagy in vivo and rejuvenates memory B cell responses. Mechanistically, spermidine post-translationally modifies the translation factor eIF5A, which is essential for the synthesis of the autophagy transcription factor TFEB. Spermidine is depleted in the elderly, leading to reduced TFEB expression and autophagy. Spermidine supplementation restored this pathway and improved the responses of old human B cells. Taken together, our results reveal an unexpected autophagy regulatory mechanism mediated by eIF5A at the translational level, which can be harnessed to reverse immune senescence in humans.


Assuntos
Autofagia/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Senescência Celular/efeitos dos fármacos , Imunossenescência/efeitos dos fármacos , Fatores de Iniciação de Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Espermidina/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Fatores Etários , Envelhecimento , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/deficiência , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Células HEK293 , Humanos , Memória Imunológica/efeitos dos fármacos , Células Jurkat , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células NIH 3T3 , Fatores de Iniciação de Peptídeos/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Fator de Iniciação de Tradução Eucariótico 5A
5.
Pharmacology ; 109(1): 34-42, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38011839

RESUMO

INTRODUCTION: Hyperuricemia may be involved in the phenotypic transformation of vascular smooth muscle cells, thus promoting the occurrence of atherosclerosis, and autophagy may be one of the important links, but little is known about the specific molecular mechanism. METHODS: We established a mouse model of hyperuricemia and studied the relationship between changes in autophagy levels and the phenotypic transformation of muscle cells. RESULTS: Our study found that high uric acid levels promote the phenotypic transformation of muscle cells by inhibiting autophagy, thus enhancing their proliferation and migration abilities. If autophagy is restored, phenotypic transformation can be reversed by reducing the levels of the transcription factor Kruppel-like factor 4. CONCLUSION: Uric acid may induce the phenotypic transformation of muscle cells and promote the occurrence of atherosclerosis by disrupting normal autophagy.


Assuntos
Aterosclerose , Hiperuricemia , Camundongos , Animais , Ácido Úrico , Hiperuricemia/induzido quimicamente , Músculo Liso Vascular , Autofagia , Miócitos de Músculo Liso , Aterosclerose/induzido quimicamente , Proliferação de Células , Células Cultivadas
6.
J Eur Acad Dermatol Venereol ; 38(1): 102-111, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37712456

RESUMO

BACKGROUND: Previous observational studies reported altered melanoma risks in relation to many potential factors, such as coffee intake, smoking habits and photodamage-related conditions. Considering the susceptibility of epidemiological studies to residual confounders, there remains uncertainty about the actual causal roles of these reported factors in melanoma aetiology. OBJECTIVES: This study aims to investigate the causal association between cutaneous melanoma (CM) and previously reported factors: coffee intake, alcohol consumption, lifetime smoking, socioeconomic status (SES), ease of skin tanning, childhood sunburn and facial ageing, providing insight into its underlying aetiology and preventative strategies. METHODS: We utilized a two-sample MR analysis on data from the largest meta-analysis summary statistics of confirmed cutaneous melanoma including 30,134 patients. Genetic instrumental variables were constructed by identifying single nucleotide polymorphisms (SNPs) that associate with corresponding factors. Inverse variance weighted (IVW) was the primary MR method. For sensitivity and heterogeneity, MR Egger, weighted median, simple mode, weighted mode and MR Egger intercept tests were examined. RESULTS: Cutaneous melanoma risks were found to be elevated in association with a predisposition towards ease of skin tanning (IVW: OR = 2.842, 95% CI 2.468-3.274, p < 0.001) and with childhood sunburn history (IVW: OR = 6.317, 95% CI 4.479-8.909, p < 0.001). Repeated MR after removing potential confounders and outliers demonstrated resolved horizontal pleiotropy and statistically significant results that closely mirrored the initial findings. Other potential factors, such as coffee intake, alcohol consumption, smoking and socioeconomic status (SES), indicated insignificant effects on melanoma risk in the analysis, and therefore, our Mendelian randomization study does not support their roles in modifying melanoma risks. CONCLUSIONS: Our extensive MR analysis provides strong evidence of the causative role of ease of skin tanning and childhood sunburn history in elevating melanoma risk. Curtailing ultraviolet radiation (UVR) exposure may be the single best preventative strategy to reduce melanoma risk.


Assuntos
Melanoma , Neoplasias Cutâneas , Queimadura Solar , Humanos , Criança , Melanoma/genética , Neoplasias Cutâneas/genética , Queimadura Solar/complicações , Café , Análise da Randomização Mendeliana , Raios Ultravioleta , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla
7.
Biochem Genet ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039322

RESUMO

Increasing studies have shown that nuclear respiratory factor 1 (NRF1) deficiency frequently occurs in many human diseases, and its activation can protect neurons and other cells from degenerative diseases and malignant tumors. However, how NRF1 is regulated in bladder cancer remains unknown. Our research aims to reveal the role of leavage and polyadenylation-specific factor 4 (CPSF4) on the growth inhibition effect of bladder cancer and clarify its relationship with NRF1. Here, cell proliferation assay, transwell migration assay and multicellular tumor spheroids (MCTS) formation assay in the bladder cancer cell lines were carried out to measure tumor cell growth. Western bolt assay was carried out to identify the relationship between NRF1 and CPSF4. Also, subcutaneous xenograft tumors in nude mice were established to further validate the inhibition effect of CPSF4 on bladder tumor and the regulation on NRF1. The results in vitro showed that knockdown of CPSF4 strongly reduced the proliferation and migration, and inhibited MCTS formation in 5637 and HT1376 cell lines, while an additional knockdown of increased NRF1 induced by CPSF4 knockdown partially abolished these effects. The results in vivo showed that knockdown of CPSF4 strongly reduced the volume and weight of subcutaneous tumor, and decreased the expression of Ki-67 in tumor tissue, while NRF1 knockdown partially reversed these effects induced by CPSF4 knockdown. Western bolt assay demonstrated that CPSF4 could negatively regulate NRF1. Our results indicated that knock-down of CPSF4 inhibited bladder cancer cell growth by upregulating NRF1, which might provide evidence of CPSF4 as a therapeutic target for bladder cancer.

8.
J Med Virol ; 95(8): e29035, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37605995

RESUMO

Recombinant LL-37 Lactococcus lactis (Oral LL-37) was designed to prevent progression of COVID-19 by targeting virus envelope, however, effectiveness and safety of Oral LL-37 in clinical application was unclear. A total of 238 adult inpatients, open-labelled, randomized, placebo-controlled, single-center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS-CoV-2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL-37 could significantly shorten NCT (LL-37 9.80 ± 2.67 vs. placebo 14.04 ± 5.89, p < 0.01). For Oral LL-37, as early as treated in 6 days, the adjusted hazard ratio (HR) for a primary event of nucleic acid negative outcome was 6.27-fold higher than 7-day-later (HR: 6.276, 95% confidence interval [CI]: 3.631-10.848, p < 0.0001), and the adjusted HR of Oral LL-37 within 6 days is higher than placebo (HR: 2.427 95% CI: 1.239-4.751, p = 0.0097). No severe AEs were observed during hospitalization and follow-up investigation. This study shows that early intervention of Oral LL-37 incredibly reduces NCT implying a potential for clearance of Omicron BA.5.1.3 without evident safety concerns.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , COVID-19/prevenção & controle , RNA Viral , Hospitalização , Pacientes Internados
9.
Cell Biol Toxicol ; 39(6): 2665-2684, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36746840

RESUMO

OBJECTIVES: To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calcific aortic valve disease (CAVD). BACKGROUND: The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited. METHODS: In vivo, we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice and used high methionine diet (HMD) to assess of aortic valve calcification lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). In vitro, the role of Herpud1 in the Hcy-related osteogenic differentiation of AVICs was investigated by manipulating of Herpud1 expression. RESULTS: Herpud1 was highly expressed in calcified human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. Herpud1 deficiency inhibited hcy-induced CAVD in vitro and in vivo. Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. ERS inhibitor 4-phenyl butyric acid (4-PBA) significantly attenuated aortic valve calcification in HMD-fed low-density lipoprotein receptor-/- (LDLR-/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis. CONCLUSIONS: These findings identify a previously unknown mechanism of Herpud1 upregulation in Hcy-related CAVD, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression. HIGHLIGHTS: • Herpud1 is upregulated in the leaflets of Hcy-treated mice and patients with CAVD. • In mice, global knockout of Herpud1 alleviates aortic valve calcification and Herpud1 silencing activates cell autophagy, inhibiting osteogenic differentiation of AVICs induced by Hcy. • 4-PBA suppressed Herpud1 expression to alleviate AVIC calcification in Hcy treated AVICs and to mitigate aortic valve calcification in mice.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Humanos , Camundongos , Animais , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Osteogênese , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Fatores de Transcrição/metabolismo , Lipoproteínas LDL/metabolismo , Células Cultivadas , Proteínas de Membrana/metabolismo
10.
J Environ Manage ; 342: 118108, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37201390

RESUMO

The performance, microbial enzymatic activity and microbial community of a sequencing batch reactor (SBR) were explored under instantaneous Cd(II) shock loading. After a 24-h Cd(II) shock loading of 100 mg/L, the chemical oxygen demand and NH4+-N removal efficiencies decreased significantly from 92.73% and 99.56% on day 22 to 32.73% and 43% on day 24, respectively, and then recovered to the normal values gradually. The specific oxygen utilization rate (SOUR), specific ammonia oxidation rate (SAOR), specific nitrite oxidation rate (SNOR), specific nitrite reduction rate (SNIRR) and specific nitrate reduction rate (SNRR) decreased by 64.81%, 73.28%, 77.77%, 56.84% and 52.46% on day 23 in comparison with the absence of Cd(II) shock loading, respectively, and they gradually returned to the normal levels. The changing trends of their associated microbial enzymatic activities including dehydrogenase, ammonia monooxygenase, nitrite oxidoreductase, nitrite reductase and nitrate reductase were in accordance with SOUR, SAOR, SNOR, SNIRR and SNRR, respectively. Cd(II) shock loading promoted the microbial reactive oxygen species production and lactate dehydrogenase release, indicating that instantaneous shock caused oxidative stress and damaged to cell membranes of the activated sludge. The microbial richness and diversity, and the relative abundance of Nitrosomonas and Thauera obviously decreased under the stress of Cd(II) shock loading. PICRUSt prediction showed that Cd (II) shock loading significantly affected Amino acid biosynthesis, Nucleoside and nucleotide biosynthesis. The present results are conducive to take adequate precautions to reduce the adverse effect on bioreactor performance in wastewater treatment systems.


Assuntos
Cádmio , Microbiota , Nitritos , Esgotos , Nitrificação , Oxigênio , Reatores Biológicos , Nitrogênio/análise , Eliminação de Resíduos Líquidos/métodos
11.
Int Wound J ; 20(1): 155-163, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35751432

RESUMO

We performed a meta-analysis to evaluate the effect of platelet-rich plasma vs standard management for the treatment of diabetic foot ulcer wounds. A systematic literature search up to March 2022 was performed and 1435 subjects with diabetic foot ulcer wounds at the baseline of the studies; 723 of them were treated with platelet-rich plasma, and 712 used control. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to assess the effect of platelet-rich plasma vs standard management for the treatment of diabetic foot ulcer wounds using the dichotomous method with a random or fixed-effect model. The use of autologous platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control (OR, 1.95; 95% CI, 1.49-2.56, P < 0.001). The use of allogeneic platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control (OR, 6.19; 95% CI, 2.32-16.56, P < 0.001). The use of autologous and allogeneic platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control. Though, the analysis of outcomes should be with caution because of the low number of studies in certain comparisons, for example, allogeneic platelet-rich plasma compared with control.


Assuntos
Diabetes Mellitus , Pé Diabético , Plasma Rico em Plaquetas , Humanos , Pé Diabético/terapia , Cicatrização
12.
Am J Physiol Endocrinol Metab ; 323(1): E69-E79, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35575231

RESUMO

Brown adipose tissue (BAT) is the primary site of adaptive thermogenesis, which is involved in energy expenditure and has received much attention in the field of obesity treatment. By screening a small-molecule compound library of drugs approved by the Food and Drug Administration, pantothenic acid was identified as being able to significantly upregulate the expression of uncoupling protein 1 (UCP1), a key thermogenic protein found in BAT. Pantothenate (PA) treatment decreased adiposity, reversed hepatic steatosis, and improved glucose homeostasis by increasing energy expenditure in C57BL/6J mice fed a high-fat diet. PA also significantly increased BAT activity and induced beige adipocytes formation. Mechanistically, the beneficial effects were mediated by UCP1 because PA treatment was unable to ameliorate obesity in UCP1 knockout mice. In conclusion, we identified PA as an effective BAT activator that can prevent obesity and may represent a promising strategy for the clinical treatment of obesity and related metabolic diseases.NEW & NOTEWORTHY PA treatment effectively and safely protected against obesity via the BAT-UCP1 axis. PA has therapeutic potential for treating obesity and type II diabetes.


Assuntos
Tecido Adiposo Marrom , Diabetes Mellitus Tipo 2 , Tecido Adiposo Marrom/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Termogênese , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
13.
BMC Plant Biol ; 22(1): 334, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35820829

RESUMO

BACKGROUND: Wuzhimaotao (Radix Fici Hirtae) originates from the dry root of Ficus hirta (Moraceae), which is widely known as a medical and edible plant distributed in South China. As the increasing demand for Wuzhimaotao, the wild F. hirta has been extremely reduced during the past years. It is urgent to protect and rationally develop the wild resources of F. hirta for its sustainable utilization. However, a lack of genetic background of F. hirta makes it difficult to plan conservation and breeding strategies for this medical plant. In the present study, a total of 414 accessions of F. hirta from 7 provinces in southern China were evaluated for the population genetics using 9 polymorphic SSR markers. RESULTS: A mean of 17.1 alleles per locus was observed. The expected heterozygosity (He) varied from 0.142 to 0.861 (mean = 0.706) in nine SSR loci. High genetic diversity (He = 0.706, ranged from 0.613 to 0.755) and low genetic differentiation among populations (G'ST = 0.147) were revealed at population level. In addition, analysis of molecular variance (AMOVA) indicated that the principal molecular variance existed within populations (96.2%) was significantly higher than that among populations (3.8%). Meanwhile, the three kinds of clustering methods analysis (STRUCTURE, PCoA and UPGMA) suggested that the sampled populations were clustered into two main genetic groups (K = 2). Mantel test showed a significant correlation between geographic and genetic distance among populations (R2 = 0.281, P < 0.001). Pollen flow, seed flow and/or geographical barriers might be the main factors that formed the current genetic patterns of F. hirta populations. CONCLUSIONS: This is a comprehensive study of genetic diversity and population structure of F. hirta in southern China. We revealed the high genetic diversity and low population differentiation in this medicinal plant and clarified the causes of its current genetic patterns. Our study will provide novel insights into the exploitation and conservation strategies for F. hirta.


Assuntos
Ficus , Cruzamento , Ficus/genética , Variação Genética , Genética Populacional , Repetições de Microssatélites/genética
14.
Plant Biotechnol J ; 20(10): 1888-1901, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35678495

RESUMO

Characterization and genetic engineering of plant transporters involved in the pesticide uptake and translocation facilitate pesticide relocation to the tissue where the pests feed, thus improving the bioavailability of the agrichemicals. We aimed to identify thiamethoxam (THX) transporters in rice and modify their expression for better brown planthopper (BPH) control with less pesticide application. A yeast library expressing 1385 rice transporters was screened, leading to the identification of an amino acid transporter-like (ATL) gene, namely OsATL15, which facilitates THX uptake in both yeast cells and rice seedlings. In contrast to a decrease in THX content in osatl15 knockout mutants, ectopic expression of OsATL15 under the control of the CaMV 35S promoter or a vascular-bundle-specific promoter gdcsPpro significantly increased THX accumulation in rice plants, thus further enhancing the THX efficacy against BPH. OsATL15 was localized in rice cell membrane and abundant in the root transverse sections, vascular bundles of leaf blade, and stem longitudinal sections, but not in hull and brown rice at filling stages. Our study shows that OsATL15 plays an essential role in THX uptake and its systemic distribution in rice. OsATL15 could be valuable in achieving precise pest control by biotechnology approaches.


Assuntos
Hemípteros , Oryza , Praguicidas , Animais , Agroquímicos/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Hemípteros/genética , Oryza/metabolismo , Praguicidas/metabolismo , Saccharomyces cerevisiae , Tiametoxam/metabolismo
15.
HIV Med ; 23 Suppl 1: 23-31, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35293105

RESUMO

OBJECTIVES: HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical presentation, laboratory findings and pathological spectrum of different subtypes of HIV-associated kidney disease in China. METHODS: Eighteen HIV patients with renal biopsy indications at the Peking Union Medical College Hospital from January 2002 to October 2021 were retrospectively enrolled. All had CD4 counts and HIV viral load measurements. Renal biopsies were examined with light microscopy, immunofluorescence, and electron microscopy. Shapiro-Wilk test was used to test whether the data was normally distributed. The data is presented as medians (interquartile range), number (%), or means (±SD) according to their distribution. RESULTS: Seventeen patients had glomerular disease, and one patient had interstitial nephritis. Membranous nephropathy was present in eight patients (47.1%), and IgA nephropathy in four patients (23.5%). The difference in urine protein and serum albumin before and after treatment was statistically significant and no deaths or dialysis were observed to the end of follow-up. CONCLUSION: This study found that classic HIV-associated nephropathy (HIVAN) was uncommon in Chinese HIV patients. HIV immune complex kidney (HIVICK) disease, such as membranous or IgA nephropathy, was more common, and associated with better prognosis. Antiretroviral therapy, ACE inhibitors, and angiotensin II receptor blockers were effective in decreasing proteinuria and preserving renal function. The use of corticosteroids and immunosuppressive agents seems safe. However, the nephrotoxic effect of antiretroviral agents and other medications should be carefully monitored.


Assuntos
Nefropatia Associada a AIDS , Glomerulonefrite por IGA , Infecções por HIV , Nefropatia Associada a AIDS/tratamento farmacológico , Biópsia , Feminino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Rim/fisiologia , Masculino , Estudos Retrospectivos
16.
Toxicol Appl Pharmacol ; 452: 116179, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914558

RESUMO

Doxorubicin (DOX) is a potent anthracycline antineoplastic drug. However, its dose-dependent cardiotoxicity limits its clinical application. Ononin is a natural isoflavone glycoside that is crucial in modulating apoptosis-related signaling pathways. In this study, we assessed the possible cardioprotective effects of ononin in DOX-induced cardiotoxicity and elucidated the underlying molecular mechanisms. In vitro and in vivo assessments were performed using DOX-treated H9C2 cells and rats, respectively. First, DOX was injected into the tail veins of Wistar rats to induce cardiomyopathy. Next, rats in the DOX + Ononin30 and DOX + Ononin60 groups were intragastrically administered ononin two weeks before DOX treatment. H9C2 cells were treated with vehicle or DOX with or without ononin. Next, 3-TYP was used to determine the relationship between endoplasmic reticulum (ER) stress and sirtuin 3 (SIRT3) expression. Ononin treatment ameliorated DOX-induced myocardial injury as determined by echocardiography. Furthermore, ononin partially restored DOX-induced cardiac dysfunction; the left ventricular ejection fraction (LVEF) and left ventricular systolic fractional shortening (LVFS) increased after pre-treatment with ononin. Further, ononin suppressed DOX-induced ER stress and apoptosis in rat cardiomyocytes and H9C2 cells. The Bax/Bcl-2 ratio and 78-kD glucose-regulated protein (GRP78) and CCAAT enhancer-binding protein (CHOP) expression levels were higher in the DOX-treated group than in the control group but ononin treatment improved these parameters. These effects are associated with SIRT3 activity. Moreover, 3-TYP blocked the ononin-mediated protective effects. Hence, ononin positively affected DOX-induced cardiotoxicity by inhibiting ER stress and apoptosis, possibly mediated by stimulation of the SIRT3 pathway.


Assuntos
Isoflavonas , Sirtuína 3 , Animais , Apoptose , Cardiotoxicidade/metabolismo , Doxorrubicina/farmacologia , Estresse do Retículo Endoplasmático , Glucosídeos , Isoflavonas/farmacologia , Miócitos Cardíacos , Estresse Oxidativo , Ratos , Ratos Wistar , Sirtuína 3/metabolismo , Volume Sistólico , Função Ventricular Esquerda
17.
Biotechnol Lett ; 44(10): 1149-1162, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36006576

RESUMO

OBJECTIVES: We constructed a recombinant oral GLP-1 analogue in Lactococcus lactis (L. lactis) and evaluated its physiological functions. RESULTS: In silico docking suggested the alanine at position 8 substituted with serine (A8SGLP-1) reduced binding of DPP4, which translated to reduced cleavage by DPP4 with minimal changes in stability. This was further confirmed by an in vitro enzymatic assay which showed that A8SGLP-1 significantly increased half-life upon DPP4 treatment. In addition, recombinant L. lactis (LL-A8SGLP-1) demonstrated reduced fat mass with no changes in body weight, significant improvement of random glycemic control and reduced systemic inflammation compared with WT GLP-1 in db/db mice. CONCLUSION: LL-A8SGLP-1 adopted in live biotherapeutic products reduce blood glucose in db/db mice without affecting its function.


Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Alanina/uso terapêutico , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Dipeptidil Peptidase 4/metabolismo , Dipeptidil Peptidase 4/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Serina
18.
J Environ Manage ; 315: 115149, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35500485

RESUMO

Coal gasification is one of the most promising clean coal technologies. However, gasification process also produces a huge amount of solid waste of high carbon content, named coal gasification fine slag. The coal gasification fine slag is mainly handled by landfilling, which is not only a hazardous pollution, but also wasting the energy from residual carbon. Developing a technology to utilize coal gasification fine slag and recover the residual carbon is becoming essential for an eco-friendly coal chemical industry. In this paper, the enrichment behavior of residual carbon in coal gasification fine slag by a spiral separator is studied. The raw coal gasification fine slag sample and separator products are characterized on particle size distribution, size-depending ash content, reactivity, micromorphology and porous structure. The experimental results show that the spiral separator is efficient to remove ash and enriched carbonaceous components in coal gasification fine slag by separating feed (100%) into concentrate (81.2%), middlings (8.8%), and tailings (10.08%), where the ash content in tailings is up to 90%, accounting for 18.5% of total ash in feeding. The beneficial product "concentrate" has a good distribution of size-depending ash content, that most combustibles are enriched in these particles of diameter >100 µm. After spiral separator, the concentrate products have a more pure and developed porous structure with the surface area increasing from 199.8 m2/g (feeding) to 231.8 m2/g, as well as a better combustion reactivity of lower ignition temperature compared with feedings. Accordingly, an economic and feasible combination process of spiral separator connecting sieve can produce an enriched-carbon product of ∼45% yield and ∼80% carbonaceous content. The Iodine adsorption ability of sieved products increases by 47.6% compared with feed, and reaches up to about half of industry activated carbon. The finally sieved concentrate products have a good market prospect as fuel and adsorbent.

19.
Omega (Westport) ; 84(4): 1146-1159, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32515268

RESUMO

The body donation program of Peking Union Medical College was established in May 1999. From May 1999 to December 2017, a total of 5,576 registrants registered and 1,459 donors donated their bodies. Demographic and medical characteristics of the donors were analyzed. The top four causes of death were neoplasms, heart diseases, respiratory diseases, and cerebrovascular diseases. Age at death among donors who died of neoplasms were significantly lower than other causes of death (all p < .05), and the interval between registration and donation among donors who died of neoplasms was significantly shorter than that among donors with other causes (all p < .001). The age of donors when they registered (p < .001) and donated (p < .001) was significantly older than that of general Beijing population. This study may provide a guide for medical colleges or research institutions to establish or enhance their own body donation programs.


Assuntos
Anatomistas , Estudantes de Medicina , Cadáver , China , Humanos , Doadores de Tecidos , Universidades
20.
Small ; 17(13): e2006496, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33656798

RESUMO

Silicon-based semiconductor materials dominate modern technology for more than half a century with extraordinary electrical-optical performance and mutual processing compatibility. Now, 2D materials have rapidly established themselves as prospective candidates for the next-generation semiconductor industry because of their novel properties. Considering chemical and processing compatibility, silicon-based 2D materials possess significant advantages in integrating with silicon. Here, a systematic study is reported on the structural, electrical, and optical performance of silicon telluride (Si2 Te3 ) 2D material, a IV-VI silicon-based semiconductor with a layered structure. The ultrawide photoluminescence (PL) spectra in the range of 550-1050 nm reveals the intrinsic defects in Si2 Te3 . The Si2 Te3 -based field-effect transistors (FETs) and photodetectors show a typical p-type behavior and a remarkable broadband spectral response in the range of 405-1064 nm. Notably, the photoresponsivity and detectivity of the photodetector device with 13.5 nm in thickness and upon 405 nm illumination can reach up to 65 A W-1 and 2.81 × 1012 Jones, respectively, outperforming many traditional broadband photodetectors. It is believed this work will excite interests in further exploring the practical application of 2D silicon-based materials in the field of optoelectronics.

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