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Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH.
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Exossomos , Hipertensão Pulmonar , Células-Tronco Mesenquimais , Hipertensão Arterial Pulmonar , Humanos , Camundongos , Animais , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/metabolismo , Exossomos/metabolismo , Remodelação Vascular , Cordão Umbilical/metabolismo , Hipóxia/complicações , Hipóxia/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , Células-Tronco Mesenquimais/metabolismoRESUMO
Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-ß1/Smad2/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGFß pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGFß1 and p-Smad2/3. Furthermore, TGFß1 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGFß1/Smad2/3 pathway via Nbl1.
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Exossomos , Hipertensão Pulmonar , Hipóxia , Células-Tronco Mesenquimais , Remodelação Vascular , Animais , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Remodelação Vascular/fisiologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/patologia , Ratos , Hipóxia/metabolismo , Ratos Sprague-Dawley , Masculino , Tibet , Humanos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Fator de Crescimento Transformador beta1/metabolismo , Proliferação de Células , Transdução de Sinais , Modelos Animais de Doenças , Proteína Smad2/metabolismoRESUMO
Natural Nicotinamide Adenine Dinucleotide (NAD+) precursors have attracted much attention due to their positive effects in promoting ovarian health. However, their target tissue, synthesis efficiency, advantages, and disadvantages are still unclear. This review summarizes the distribution of NAD+ at the tissue, cellular and subcellular levels, discusses its biosynthetic pathways and the latest findings in ovary, include: (1) NAD+ plays distinct roles both intracellularly and extracellularly, adapting its distribution in response to requirements. (2) Different precursors differs in target tissues, synthetic efficiency, biological utilization, and adverse effects. Importantly: tryptophan is primarily utilized in the liver and kidneys, posing metabolic risks in excess; nicotinamide (NAM) is indispensable for maintaining NAD+ levels; nicotinic acid (NA) constructs a crucial bridge between intestinal microbiota and the host with diverse functions; nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) increase NAD+ systemically and can be influenced by delivery route, tissue specificity, and transport efficiency. (3) The biosynthetic pathways of NAD+ are intricately intertwined. They provide multiple sources and techniques for NAD+ synthesis, thereby reducing the dependence on a single molecule to maintain cellular NAD+ levels. However, an excess of a specific precursor potentially influencing other pathways. In addition, Protein expression analysis suggest that ovarian tissues may preferentially utilize NAM and NMN. These findings summarize the specific roles and potential of NAD+ precursors in enhancing ovarian health. Future research should delve into the molecular mechanisms and intervention strategies of different precursors, aiming to achieve personalized prevention or treatment of ovarian diseases, and reveal their clinical application value.
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NAD , Niacinamida , Ovário , Humanos , NAD/metabolismo , NAD/biossíntese , Ovário/metabolismo , Feminino , Animais , Niacinamida/metabolismo , Niacinamida/biossíntese , Vias Biossintéticas , Mononucleotídeo de Nicotinamida/metabolismoRESUMO
BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.
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Bronquiectasia , Humanos , Bronquiectasia/microbiologia , Bronquiectasia/diagnóstico , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Estudos de Coortes , Seguimentos , Adulto , Progressão da Doença , Estudos LongitudinaisRESUMO
A novel polymeric ionic liquid (PDBA-IL-NH2) using imidazolium ionic liquids with short alkyl chains as monomers and two control ionic liquids (PDBA-IL-OH and PIL-NH2) were synthesized. Their inhibition properties and mechanisms were explored via surface analysis, weight loss tests, electrochemical studies, and adsorption isotherm analysis. The corrosion inhibition efficiency (CIE) of PDBA-IL-NH2 gradually increased with increasing concentration, and the largest efficiency was 94.67% at 100 ppm. At the same concentration (50 ppm), the corrosion inhibition abilities of inhibitors were in the order of PDBA-IL-NH2 > PDBA-IL-OH > PIL-NH2 > IL-NH2. Based on the experimental investigation, the synergistic effect of electrostatic interaction, protonation, and electron donor-acceptor interaction facilitated the intensive entanglement and coverage of PDBA-IL-NH2 with the reticulated form on the metal, and the generated densest films protected the metal from the corrosive media. Ultimately, the theoretical results of molecular dynamics simulations and quantum chemical study were in high agreement with the experimental data, which confirmed the proposed inhibition mechanisms on the microscopic scale. This study contributed valuable perspectives to the design of efficient and ecofriendly corrosion inhibitors.
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Hydrate-based CO2 storage in the ocean is considered a potential method for mitigating the greenhouse effect. Numerous studies demonstrated that NaCl exhibited the dual effects of promotion and inhibition in the nucleation and growth processes of CO2 hydrate, whose mechanisms remain unclear. In this study, the effects of NaCl at various concentrations on the CO2 hydrate growth and crystal are investigated. The independent gradient model based on Hirshfeld partition, electrostatic potential, and binding energy is conducted to study the interaction between ions and water molecules. The motion trajectories of ions are observed at the molecular level to reflect the impact of ion motion on hydrate growth. The results show that the influence of NaCl on hydrate growth depends on a delicate balance of dual promotion-inhibition effects. NaCl can combine more water molecules and provide a transport channel of CO2 to promote hydrate growth at low concentrations. Meanwhile, the promoting effects shift toward inhibition with increasing NaCl concentrations. In a word, this paper proposes a novel mechanism for the dual promotion-inhibition effects of NaCl on hydrate growth, which is significant for further research on hydrate-based CO2 storage in the ocean.
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Great aqueous dispersibility, a large specific surface area, and high impermeability make graphene oxide (GO) the ideal candidate for a high-performance corrosion inhibitor. Numerous symmetrical modification methods have been reported to enhance the adsorption of GO on metal surfaces in various corrosive media. This work aims to investigate the enhancement and mechanism of unilateral hydrophobic modification on the corrosion inhibition performance of GO. In this study, amphiphilic Janus GO (JGO) was prepared by grafting hydrophobic alkyl chains on one side of GO, and its anticorrosion performance was evaluated via weight loss experiments and electrochemical tests. The results revealed that the corrosion inhibition efficiency for Q235 mild steel (MS) in a 1 M HCl aqueous solution of 25 ppm JGO (81.08%) was much higher than that of GO at the same concentration (22.12%). Furthermore, the Langmuir adsorption isotherm and computational study demonstrated that the synergistic effect of physical adsorption and chemical adsorption promoted the hydrophilic side of JGO close to the surface of the metal, and the dense protective layer was formed by the hydrophobic chains toward the corrosive medium, which effectively hindered the corrosion of MS by the acidic liquid. This study emphasizes the significant role of asymmetrically modified hydrophobic alkyl chains in improving the corrosion prevention performance of GO and provides a perspective for the structural design of GO-based corrosion inhibitors.
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Our recent multi-omics studies have revealed rich sources of novel bioactive proteins and polypeptides from marine organisms including cnidarians. In the present study, we initially conducted a transcriptomic analysis to review the composition profile of polypeptides from Zoanthus sociatus. Then, a newly discovered NPY-like polypeptide-ZoaNPY was selected for further in silico structural, binding and virtually pharmacological studies. To evaluate the pro-angiogenic effects of ZoaNPY, we employed an in vitro HUVECs model and an in vivo zebrafish model. Our results indicate that ZoaNPY, at 1-100 pmol, enhances cell survival, migration and tube formation in the endothelial cells. Besides, treatment with ZoaNPY could restore a chemically-induced vascular insufficiency in zebrafish embryos. Western blot results demonstrated the application of ZoaNPY could increase the phosphorylation of proteins related to angiogenesis signaling including PKC, PLC, FAK, Src, Akt, mTOR, MEK, and ERK1/2. Furthermore, through molecular docking and surface plasmon resonance (SPR) verification, ZoaNPY was shown to directly and physically interact with NPY Y2 receptor. In view of this, all evidence showed that the pro-angiogenic effects of ZoaNPY involve the activation of NPY Y2 receptor, thereby activating the Akt/mTOR, PLC/PKC, ERK/MEK and Src- FAK-dependent signaling pathways. Furthermore, in an excision wound model, the treatment with ZoaNPY was shown to accelerate the wound healing process in mice. Our findings provide new insights into the discovery and development of novel pro-angiogenic drugs derived from NPY-like polypeptides in the future.
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Cnidários , Peptídeos , Receptores de Neuropeptídeo Y , Animais , Humanos , Camundongos , Movimento Celular/efeitos dos fármacos , Quinase 1 de Adesão Focal/efeitos dos fármacos , Quinase 1 de Adesão Focal/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Ligantes , Simulação de Acoplamento Molecular , Neovascularização Fisiológica/efeitos dos fármacos , Neuropeptídeo Y/metabolismo , Neuropeptídeo Y/farmacologia , Peptídeos/farmacologia , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , Receptores de Neuropeptídeo Y/efeitos dos fármacos , Receptores de Neuropeptídeo Y/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinases da Família src/efeitos dos fármacos , Quinases da Família src/metabolismo , Peixe-Zebra , Cnidários/química , Fosfoinositídeo Fosfolipase C/efeitos dos fármacos , Fosfoinositídeo Fosfolipase C/metabolismoRESUMO
A clear and accurate assessment of depressive symptoms among people living with HIV/AIDS (PLWHA) in the past five years is essential to help develop reasonable and sound interventions to improve their depressive symptoms. PubMed, Web of Science, MEDLINE, Cochrane, Embase, CINAHL, and APA were searched from 1 January 2017 to 12 April 2022. The data were analyzed using STATA 15 Software to pool the global prevalence of depressive symptoms in PLWHA. Ultimately, 103785 PLWHA from 81 original studies were included. The pooled analysis showed that the global prevalence of depressive symptoms in PLWHA over the past five years was 0.35 (95% CI: 0.31-0.38), with differences in depressive symptoms in PLWHA by geographic location, gender, assessment instruments, alcohol use, smoking, marriage, co-morbid disease, financial situation, and educational level. Scientific and timely public health interventions should be developed among PLWHA to improve their depressive symptoms and thereby improve mental health and clinical outcomes.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/epidemiologia , Prevalência , Depressão/epidemiologia , Depressão/psicologia , ComorbidadeRESUMO
The flexible electronic sensor is a critical component of wearable devices, generally requiring high stretchability, excellent transmittance, conductivity, self-healing capability, and strong adhesion. However, designing ion-conducting elastomers meeting all these requirements simultaneously remains a challenge. In this study, a novel approach is presented to fabricate highly stretchable, transparent, and self-healing ion-conducting elastomers, which are synthesized via photo-polymerization of two polymerizable deep eutectic solvents (PDESs) monomers, i.e., methacrylic acid (MAA)/choline chloride (ChCl) and itaconic acid (IA)/ChCl. The as-prepared ion-conducting elastomers possess outstanding properties, including high transparency, conductivity, and the capability to adhere to various substrates. The elastomers also demonstrate ultra-stretchability (up to 3900%) owing to a combination of covalent cross-linking and noncovalent cross-linking. In addition, the elastomers can recover up to 3250% strain and over 94.5% of their original conductivity after self-healing at room temperature for 5 min, indicating remarkable mechanical and conductive self-healing abilities. When utilized as strain sensors to monitor real-time motion of human fingers, wrist, elbow, and knee joints, the elastomers exhibit stable and strong repetitive electrical signals, demonstrating excellent sensing performance for large-scale movements of the human body. It is anticipated that these ion-conducting elastomers will find promising applications in flexible and wearable electronics.
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OBJECTIVES: Older people are more likely to have digital exclusion, which is associated with poor health. This study investigated the relationship between digital exclusion and cognitive impairment in older adults from 23 countries across five longitudinal surveys. DESIGN AND MEASUREMENTS: Digital exclusion is defined as self-reported non-use of the Internet. We assessed cognitive impairment on three dimensions: orientation, memory, and executive function. We used generalized estimation equations fitting binary logistic regression with exchangeable correlations to study the relationship between digital exclusion and cognitive impairment, and apply the minimum sufficiently adjusted set of causally directed acyclic graphs as the adjusted variable. SETTING AND PARTICIPANTS: We pooled a nationally representative sample of older adults from five longitudinal studies, including the China Health and Retirement Longitudinal study (CHARLS), the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS), the Mexican Health and Ageing Study (MHAS) and the Survey of Health, Ageing and Retirement in European (SHARE). RESULTS: We included 62,413 participants from five longitudinal studies. Digital exclusion varied by country, ranging from 21.69% (SHARE) in Denmark to 97.15% (CHARLS) in China. In the original model, digital exclusion was significantly associated with cognitive impairment in all five studies. In the adjusted model, these associations remained statistically significant: CHARLS (Odds ratio [OR] = 2.81, 95% confidence interval [CI] 1.84-4.28, ELSA (1.92 [1.70-2.18]), HRS(2.48[2.28-2.71), MHAS (1.92 [1.74-2.12]), and SHARE (2.60 [2.34-2.88]). CONCLUSION: Our research shows that a significant proportion of older people suffer from digital exclusion, especially in China. Digital exclusion was positively correlated with cognitive impairment. These findings suggest that digital inclusion could be an important strategy to improve cognitive function and reduce the risk of cognitive impairment in older adults.
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Disfunção Cognitiva , Humanos , Idoso , Estudos Longitudinais , Masculino , Feminino , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , China/epidemiologia , Uso da Internet/estatística & dados numéricosRESUMO
Studies have shown that the stem cell microenvironment is a key factor for stem cell maintenance or differentiation. In this study, we compared the expression of 23 cytokines such as IL-6, IL-10, and TNFα between young and aged rats during patellar tendon repair by cytokine microarray, and found that significant difference between IL-10, G-CSF, and VEGF at 3, 7, or 14 days post-operatively. The effects of these factors on adipogenic differentiation of TPSCs were examined through western blot and oil red O experiments. It was shown that VEGF had an inhibitive effect on the adipogenic differentiation of TPSCs. SPP-1 was figured out as our target by RNA sequencing and confirmed by western blot in vitro. Further in vivo studies showed that adipocyte accumulation was also decreased in the tendons of aged rats after injection of VEGF and the histological score and biomechanical property were also improved via targeting SPP-1. Furthermore, histochemical results showed that vascularization of the injury sites was significantly elevated. In conclusion, VEGF not only plays an important role in decreasing adipocyte accumulation but also improves vascularization of the tendon during aged tendon healing. We believe active regulation of VEGF may improve the treatment of age-related tendon diseases and tendon injuries.
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Interleucina-10 , Fator A de Crescimento do Endotélio Vascular , Animais , Diferenciação Celular/fisiologia , Interleucina-10/metabolismo , Ratos , Ratos Sprague-Dawley , Células-Tronco/metabolismo , Tendões , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Physical injury carried by dried process was an inevitable and hostile problem which could seriously affect the quality and viability of microbial agents. In this study, heat preadaptation was successfully applied as a pretreatment to fight against the physical stresses encountered during freeze-dried and spray-dried process and develop a high activity Tetragenococcus halophilus powder. The results indicated T. halophilus cells maintained a higher viability in dried powder when cells were treated with heat preadaptation before dried process. Flow cytometry analysis illustrated that heat preadaptation contributed to maintain a high membrane integrity during dried process. Besides, glass transition temperatures of dried powder increased when cells were preheated, which further verified that higher stability was obtained in group preadaptation during shelf life. Additionally, dried powder prepared by heat shock presented a better fermentation performance, suggesting heat preadaptation may be a promising strategy to prepare bacterial powder by freeze drying or spray drying.
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Lactobacillales , Secagem por Atomização , Pós , Liofilização/métodos , TemperaturaRESUMO
With changes in global climate, blooms are becoming more frequent and difficult to control. Therefore, the selection of algal suppressor agents with effective inhibition and environmental safety is of paramount importance. One of the main treatment strategies is to inhibit the release of harmful algal toxins. Tea polyphenols (TP) are natural products that have been widely used in medicine, the environment, and other fields due to their antibacterial and antioxidant properties. To investigate their potential application in the treatment of algal blooms, TP were applied to three different microalgae. TP exhibited strong inhibitory effects towards all three microalgae. They stimulate the accumulation of ROS in algal cells, leading to lipid peroxidation and subsequent damage to the cell membrane, resulting in the rupture and necrosis of Cyclotella sp. and Chlorella vulgaris cells. Remarkably, it was observed that lower concentrations of TP exhibited the ability to induce apoptosis in M. aeruginosa cells without causing any structural damage. This outcome is particularly significant as it reduces the potential risk of microcystin release resulting from cell rupture. Overall, blooms dominated by different algae can be treated by adjusting the concentration of TP, a new algal suppressor, indicating strong potential treatment applications.
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Chlorella vulgaris , Polifenóis , Polifenóis/farmacologia , Eucariotos , Eutrofização , Chá/química , Proliferação Nociva de AlgasRESUMO
BACKGROUND: Androgenetic alopecia can affect up to 70% of males and 40% of females; however, certain therapeutic medications offer partial and transitory improvement but with major side effects. Dendrobium officinale polysaccharide (DOP) has been reported to improve androgen-related hair loss in mice, but the molecular mechanism remains unclear. OBJECTIVES: To explore the effects of DOP on androgenetic alopecia. METHODS: In this study, testosterone was subcutaneously administered to shave dorsa skin of mice to establish androgenetic alopecia; the effects of DOP in androgenetic alopecia were explored by DOP administration. RESULTS: Testosterone treatment extended the time of skin growing dark and hair growing, decreased the mean numbers of follicles in skin tissues, decreased ß-catenin and cyclin D1 levels, and elevated testosterone, DHT (dihydrotestosterone), and 5α-reductase levels. In contrast, DOP administration shortened skin growing dark and hair growing times, promoted follicle cell proliferation, increased follicle numbers, increased ß-catenin and cyclin D1 levels, and decreased testosterone, DHT, and 5α-reductase levels. CONCLUSION: DOP application significantly improved testosterone-induced hair follicle miniaturization and hair loss, possibly through affecting the Wnt signaling and hair follicle stem cell functions. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Dendrobium , Testosterona , Masculino , Feminino , Camundongos , Animais , Testosterona/farmacologia , beta Catenina/farmacologia , Ciclina D1/farmacologia , Cabelo , Alopecia/induzido quimicamente , Alopecia/tratamento farmacológico , Polissacarídeos/farmacologiaRESUMO
AIM: Pressure injuries are a significant health care problem worldwide, and many factors influence their occurrence and development. The purpose of this systematic review and meta-analysis was to investigate the role of nutritional status in the development rate of pressure injuries as a potentially modifiable risk factor. METHODS: Study designs included cohort (prospective and retrospective), case-control, and RCTs if the association between nutrition status and pressure injuries was reported. Databases searched included: PubMed, CINAHL, Embase, Scopus, Web of Science, and Cochrane Library on April 20th, 2022. The data were analyzed using OR and random effect model in Revman5.3 and STATA 15 Software. Report this systematic review and meta-analysis according to the PRISMA 2020 statement. RESULTS: A total of 22 separate studies were retained in this systematic review. Of these, 16 articles were included in the meta-analysis. Three studies were assessed as low risk and sixteen as a moderate risk of bias. All RCTs were B quality. The odds ratio of the incidence of pressure injuries in malnourished and non-malnourished patients was 3.66(95% CI: 2.77-4.83). In the three RCTs studies(n = 870), the odds ratio of the incidence of pressure ulcers in patients with standard nutrition to those with specific nutritional interventions was 1.35(95%CI:1.02-1.78). CONCLUSIONS: This systematic review and meta-analysis showed that nutritional status is significantly associated with pressure injuries. Malnutrition can increase the incidence of pressure injuries, and specific nutritional interventions can reduce the incidence of pressure injuries compared to standard nutrition.
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Lesões por Esmagamento , Úlcera por Pressão , Humanos , Adulto , Estado Nutricional , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/etiologia , Incidência , Estudos Retrospectivos , Estudos ProspectivosRESUMO
The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and ß-boswellic acid(ß-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and ß-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of ß-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and ß-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of ß-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of ß-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of ß-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of ß-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of ß-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.
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Medicamentos de Ervas Chinesas , Lesões Pré-Cancerosas , Triterpenos , Ratos , Animais , Cromatografia Líquida , Espectrometria de Massas em Tandem , Triterpenos/farmacologiaRESUMO
The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast. Of 48 healthy female rats, 8 were randomly selected as blank group, and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast. The successfully modeled rats were randomly divided into a model group, a tamoxifen group(1.8 mg·kg~(-1)·d~(-1)), a Xihuang Pills low-dose group(0.3 g·kg~(-1)·d~(-1)), a medium-dose group(0.6 g·kg~(-1)·d~(-1)) and a high-dose group(1.2 g·kg~(-1)·d~(-1)). After 30 days of admi-nistration, the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining, and the visceral index was calculated. Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum. The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry. The protein expressions of VEGF, vascular endothelial growth factor receptor 2(VEGFR2), phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2), B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF, FGF2, CXC-chemokine receptor 4(CXCR4), cysteine aspartic acid-specific protease(caspase-3), and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR). HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue, while the Xihuang Pills high-dose group had mild hyperplasia. Compared with the model group, the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01). ELISA results showed that compared with the model group, expressions of E_2 and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01). Immunohistochemistry, Western blot and RT-PCR indicated that compared with the conditions in the model group, the protein and mRNA expressions of VEGF and FGF2 in the Xihuang Pills groups were down-regulated(P<0.05 or P<0.01), and the protein expression of Bcl-2 was lowered(P<0.01); there was a decrease in the protein expressions of VEGFR2 and p-VEGFR2(P<0.01), a down-regulation in the mRNA expressions of CXCR4 and SDF-1(P<0.01), while an increase in the mRNA expression of caspase-3(P<0.01) in both Xihuang Pills medium-dose and high-dose groups; the protein expression of Bax in Xihuang Pills high-dose group was increased(P<0.01). The above results indicated that Xihuang Pills can effectively intervene in precance-rous lesions of the breast, and the mechanism may be related to the regulation of E_2 and P secretion as well as the inhibition of angiogenesis and chemokine receptor expression, thus controlling the occurrence of precancerous lesions of the breast in rats.
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Lesões Pré-Cancerosas , Fator A de Crescimento do Endotélio Vascular , Ratos , Feminino , Animais , Ratos Sprague-Dawley , Proteína X Associada a bcl-2 , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Caspase 3 , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Fator 2 de Crescimento de Fibroblastos , Proteínas Proto-Oncogênicas c-bcl-2 , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Hiperplasia , Receptores de Quimiocinas , RNA MensageiroRESUMO
Fluorescence imaging the interplay between lipid droplets (LDs) and protein aggregates (PAs) is extremely valuable for elucidating molecular mechanisms of aging. Here, we describe the first dual-functional fluorescent probe, LW-1, for simultaneously imaging LDs and PAs in distinct fluorescence channels to dissect interplaying roles between LDs and PAs during aging. Notably, based on an intriguing mechanism of hydrogen bonds regulating single bond rotation, LW-1 selectively detected LDs in a red channel. Meanwhile, based on another mechanism of the hydrogen bond regulating intramolecular charge transfer efficiency, probe LW-1 further detected PAs in an NIR channel. Practical applications showed that LW-1 was capable of concurrently detecting LDs and PAs in living cells. Moreover, simultaneously imaging LDs and PAs in intestine tissues of mice at different aging degrees was conducted. The results denoted that the PAs level in the intestine tissue increased dramatically with aging, accompanying the buildup of LDs. Significantly, the interplay between LDs and PAs during aging was observed. These evidences demonstrated that the PAs level was closely related with aging processes in intestine tissues, while LDs were formed correspondingly to interact with PAs, suggesting that excessive PAs can be loaded into LDs and then be removed by lipophagy.
Assuntos
Corantes Fluorescentes , Gotículas Lipídicas , Envelhecimento , Animais , Corantes Fluorescentes/química , Gotículas Lipídicas/química , Camundongos , Imagem Óptica/métodos , Agregados ProteicosRESUMO
BACKGROUND: It is challenging to detect pressure injuries at an early stage of their development. OBJECTIVES: To assess the ability of an infrared thermography (IRT)-based model, constructed using a convolution neural network, to reliably detect pressure injuries. METHODS: A prospective cohort study compared validity in patients with pressure injury (n = 58) and without pressure injury (n = 205) using different methods. Each patient was followed up for 10 days. RESULTS: The optimal cut-off values of the IRT-based model were 0·53 for identifying tissue damage 1 day before visual detection of pressure injury and 0·88 for pressure injury detection on the day visual detection is possible. Kaplan-Meier curves and Cox proportional hazard regression model analysis showed that the risk of pressure injury increased 13-fold 1 day before visual detection with a cut-off value higher than 0·53 [hazard ratio (HR) 13·04, 95% confidence interval (CI) 6·32-26·91; P < 0·001]. The ability of the IRT-based model to detect pressure injuries [area under the receiver operating characteristic curve (AUC)lag 0 days , 0·98, 95% CI 0·95-1·00] was better than that of other methods. CONCLUSIONS: The IRT-based model is a useful and reliable method for clinical dermatologists and nurses to detect pressure injuries. It can objectively and accurately detect pressure injuries 1 day before visual detection and is therefore able to guide prevention earlier than would otherwise be possible. What is already known about this topic? Detection of pressure injuries at an early stage is challenging. Infrared thermography can be used for the physiological and anatomical evaluation of subcutaneous tissue abnormalities. A convolutional neural network is increasingly used in medical imaging analysis. What does this study add? The optimal cut-off values of the IRT-based model were 0·53 for identifying tissue damage 1 day before visual detection of pressure injury and 0·88 for pressure injury detection on the day visual detection is possible. Infrared thermography-based models can be used by clinical dermatologists and nurses to detect pressure injuries at an early stage objectively and accurately.