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BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.
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Microbiota , Envelhecimento da Pele , Pele , Raios Ultravioleta , Humanos , Animais , Cobaias , Pele/microbiologia , Pele/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , RNA Ribossômico 16SRESUMO
Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycaemia that seriously affects human health. Diabetic cardiomyopathy (DCM) is a major cardiovascular complication and one of the main causes of death in patients with DM. Although DCM attracts great attention, and new therapeutic methods are continuously developed, there is a lack of effective treatment strategies. Therefore, exploring and targeting new signalling pathways related to the evolution of DCM becomes a hotspot and difficulty in the prevention and treatment of DCM. Pyroptosis is a newly discovered regulated cell death that is heavily dependent on the formation of plasma membrane pores by members of the gasdermin protein family and is reported to be involved in the occurrence, development, and pathogenesis of DCM. In this review, we focus on the molecular mechanisms of pyroptosis, its involvement in the relevant signalling pathways of DCM, and potential pyroptosis-targeting therapeutic strategies for the treatment of DCM. Our review provides new insights into the use of pyroptosis as a useful tool for the prevention and treatment of DCM and clarifies future research directions.
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Diabetes Mellitus , Cardiomiopatias Diabéticas , Hiperglicemia , Humanos , Cardiomiopatias Diabéticas/terapia , Piroptose , InflamassomosRESUMO
Intestinal damage and secondary bacterial translocation are caused by the inflammatory response induced by sepsis. Tongfu Lifei (TLF) decoction has a protective effect on sepsis-related gastrointestinal function injury. However, the relation between gut microbiota, immune barrier, and sepsis under the treatment of TLF have not been well clarified yet. Here, rats were subjected to cecal ligation and puncture (CLP) to create a sepsis model. Subsequently, the TLF decoction was given to CLP rats by gavage, fecal microbiota transplantation (FMT), and antibiotic were used as positive control. TLF suppressed the inflammatory response and improved the pathological changes in the intestines of CLP rats. Besides, TLF promoted the balance of the percentage of the Th17 and Treg cells. Intestinal barrier function was also improved by TLF through enhancing ZO-1, and Occludin and Claudin 1 expression, preventing the secondary translocation of other gut microbiota. TLF dramatically boosted the gut microbiota's alpha- and beta-diversity in CLP rats. Moreover, it increased the relative abundance of anti-inflammatory gut microbiota and changed the progress of the glucose metabolism. In short, TLF regulated the gut microbiota to balance the ratio of Th17/Treg cells, reducing the inflammation in serum and intestinal mucosal injury in rats.
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Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Mucosa Intestinal , Sepse , Linfócitos T Reguladores , Células Th17 , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Sepse/imunologia , Sepse/tratamento farmacológico , Sepse/complicações , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Mucosa Intestinal/microbiologia , Masculino , Ratos Sprague-DawleyRESUMO
BACKGROUND: The associations of fat distribution with bone health are debatable. We aimed to investigate the associations between neck circumference (NC) and bone mineral loss among the adult Chinese population in Sichuan province. METHODS: We examined overall NC size and NC stratums (≤35 cm, 35
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Densidade Óssea , Pescoço , Humanos , Masculino , Feminino , Densidade Óssea/fisiologia , China/epidemiologia , Estudos Transversais , Pessoa de Meia-Idade , Pescoço/anatomia & histologia , Adulto , Idoso , Colo do Fêmur/diagnóstico por imagem , Osteoporose/epidemiologia , Vértebras LombaresRESUMO
Currently, treatment options for acute lung injury (ALI) are limited. Gypenoside XLIX (Gyp-XLIX) is known for its anti-inflammatory properties, but there is a lack of extensive research on its effects against ALI. This study induced ALI in mice through cecal ligation and puncture surgery and investigated the biological activity and potential mechanisms of Gypenoside XLIX (40 mg/kg) by intraperitoneal injection. The in vitro ALI model was established using mouse lung epithelial (MLE-12) cells stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Various methods, including Hematoxylin and Eosin (H&E) staining, biochemical assay kits, Quantitative Polymerase Chain Reaction (qPCR) analysis, Western blotting, Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay, immunofluorescence, and flow cytometry, were employed for this research. The results indicated that pretreatment with Gypenoside XLIX significantly alleviated pathological damage in mouse lung tissues and reduced the expression levels of inflammatory factors. Additionally, Gypenoside XLIX inhibited ROS levels and NLRP3 inflammasome, possibly mediated by the Sirt1/Nrf2 signaling pathway. Moreover, Gypenoside XLIX significantly inhibited sepsis-induced lung cell apoptosis and excessive autophagy of mitochondria. Specifically, it suppressed mitochondrial pathway apoptosis and the Pink1/Parkin pathway of mitochondrial autophagy. These findings reveal the multifaceted effects of Gypenoside XLIX in anti-inflammatory, antioxidative, and inhibition of cell apoptosis and autophagy. This provides strong support for its therapeutic potential in sepsis-related lung injuries.
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Intestinal barrier dysfunction is a significant complication induced by sepsis, yet therapeutic strategies targeting such dysfunction remain inadequate. This study investigates the protective effects of Gypenoside XLIX (Gyp XLIX) against intestinal damage induced by sepsis. Septic intestinal injury in mice was induced by cecum ligation and puncture (CLP) surgery. The biological activity and potential mechanisms of Gyp XLIX were explored through intraperitoneal injection of Gyp XLIX (40 mg/kg). The study demonstrates that Gyp XLIX improves the pathological structural damage of the intestine and increases tight junction protein expression as well as the number of cup cells. Through activation of the nuclear factor erythroid 2-related factor 2 - Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathway, Gyp XLIX enhances antioxidant enzyme levels while reducing the excessive accumulation of reactive oxygen species (ROS). In addition, Gyp XLIX effectively alleviates sepsis-induced intestinal inflammation by inhibiting the nuclear factor kappa B (NF-κB) pathway and activation of the NLRP3 inflammasome. Moreover, Gyp XLIX inhibits cell death through modifying phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, further enhancing its ability to shield the intestinal barrier. The combined action of these molecular mechanisms promotes the restoration of immune balance and reduces excessive autophagy activity induced under septic conditions. In summary, Gyp XLIX exhibits a significant preventive action against intestinal damage brought on by sepsis, with its mechanisms involving the improvement of intestinal barrier function, antioxidative stress, inhibition of inflammatory response, and cell apoptosis. This research offers a potential strategy for addressing intestinal barrier impairment brought on by sepsis.
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Apoptose , Autofagia , Gynostemma , Inflamação , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Sepse , Animais , Estresse Oxidativo/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sepse/tratamento farmacológico , Sepse/complicações , Camundongos , Gynostemma/química , Masculino , Inflamação/tratamento farmacológico , Inflamação/patologia , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Extratos Vegetais/farmacologia , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Inflamassomos/metabolismoRESUMO
Bacterial ribonuclease E (RNase E) is vital for posttranscriptional regulation by degrading and processing RNA. The RraA protein inhibits RNase E activity through protein-protein interactions, exerting a global regulatory effect on gene expression. However, the specific role of RraA remains unclear. In this study, we investigated rraA expression in Vibrio alginolyticus ZJ-T and identified three promoters responsible for its expression, resulting in transcripts with varying 5'-UTR lengths. During the stationary phase, rraA was significantly posttranscriptionally inhibited. Deletion of rraA had no impact on bacterial growth in rich medium Luria-Bertani broth with salt (LBS) but resulted in decreased biofilm formation and increased resistance to polymyxin B. Transcriptome analysis revealed 350 differentially expressed genes (DEGs) between the wild type and the rraA mutant, while proteome analysis identified 267 differentially expressed proteins (DEPs). Integrative analysis identified 55 genes common to both DEGs and DEPs, suggesting that RraA primarily affects gene expression at the posttranscriptional level. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis demonstrated that RraA facilitates the conversion of fatty acids, propionic acid, and branched-chain amino acids to acetyl-CoA while enhancing amino acid and peptide uptake. Notably, RraA positively regulates the expression of virulence-associated genes, including those involved in biofilm formation and the type VI secretion system. This study expands the understanding of the regulatory network of RraA through transcriptome analysis, emphasizing the importance of proteomic analysis in investigating posttranscriptional regulation.IMPORTANCERraA is an inhibitor protein of ribonuclease E that interacts with and suppresses its endonucleolytic activity, thereby playing a widespread regulatory role in the degradation and maturation of diverse mRNAs and noncoding small RNAs. However, the physiological functions and associated regulon of RraA in Vibrio alginolyticus have not been fully elucidated. Here, we report that RraA impacts virulence-associated physiological processes, namely, antibiotic resistance and biofilm formation, in V. alginolyticus. By conducting an integrative analysis of both the transcriptome and proteome, we revealed the involvement of RraA in carbon metabolism, amino acid catabolism, and transport, as well as in the type VI secretion system. Collectively, these findings elucidate the regulatory influence of RraA on multiple pathways associated with metabolism and pathogenesis in V. alginolyticus.
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Proteínas de Bactérias , Biofilmes , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Proteoma , Transcriptoma , Vibrio alginolyticus , Vibrio alginolyticus/genética , Vibrio alginolyticus/metabolismo , Vibrio alginolyticus/patogenicidade , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteoma/genética , Biofilmes/crescimento & desenvolvimento , Endorribonucleases/genética , Endorribonucleases/metabolismo , Antibacterianos/farmacologiaRESUMO
The increased incidence of gallstones can be linked to previous gastrectomy (PG). However, the success rate of endoscopic retrograde cholangiopan-creatography after gastrectomy has significantly reduced. In such cases, laparoscopic transcystic common bile duct exploration (LTCBDE) may be an alternative. In this study, LTCBDE was evaluated for its safety and feasibility in patients with PG. We retrospectively evaluated 300 patients who underwent LTCBDE between January 2015 and June 2023. The subjects were divided into 2 groups according to their PG status: PG group and No-PG group. The perioperative data from the 2 groups were compared. The operation time in the PG group was longer than that in the No-PG group (184.69â ±â 20.28 minutes vs 152.19â ±â 26.37 minutes, Pâ <â .01). There was no significant difference in intraoperative blood loss (61.19â ±â 41.65 mL vs 50.83â ±â 30.47 mL, Pâ =â .087), postoperative hospital stay (6.36â ±â 1.94 days vs 5.94â ±â 1.36 days, Pâ =â .125), total complication rate (18.6 % vs 14.1 %, Pâ =â .382), stone clearance rate (93.2 % vs 96.3 %, Pâ =â .303), stone recurrence rate (3.4 % vs 1.7 %, Pâ =â .395), and conversion rate (6.8 % vs 7.0 %, Pâ =â .941) between the 2 groups. No deaths occurred in either groups. A history of gastrectomy may not affect the feasibility and safety of LTCBDE, because its perioperative results are comparable to those of patients with a history of No-gastrectomy.
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Ducto Colédoco , Estudos de Viabilidade , Gastrectomia , Laparoscopia , Humanos , Gastrectomia/métodos , Gastrectomia/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Ducto Colédoco/cirurgia , Idoso , Duração da Cirurgia , Cálculos Biliares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação/estatística & dados numéricos , Resultado do TratamentoRESUMO
Asperphenol A (1), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds (2-6). All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC50 values of 26.71 and 43.50 µM, respectively.