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1.
Biomed Pharmacother ; 180: 117480, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39357330

RESUMO

Breast cancer remains the leading cause of cancer-related morbidity and mortality among women worldwide, underscoring the urgent need for novel diagnostic and therapeutic strategies. This review explores the emerging roles of circular RNAs (circRNAs) within extracellular vesicles (exosomes) in breast cancer. circRNAs, known for their stability and tissue-specific expression, are aberrantly expressed in breast cancer and regulate critical cellular processes such as proliferation, migration, and apoptosis, positioning them as promising biomarkers. Exosomes facilitate intercellular communication by delivering circRNAs, reflecting the physiological and pathological state of their source cells. This review highlights the multifaceted roles of exosomal circRNAs in promoting tumor growth, metastasis, and drug resistance through their modulation of tumor metabolism, the tumor microenvironment, and immune responses. In particular, we emphasize their contributions to chemotherapy resistance and their potential as both diagnostic markers and therapeutic targets. By synthesizing current research, this review provides novel insights into the clinical applications of exosomal circRNAs, offering a foundation for future studies aimed at improving breast cancer management through non-invasive diagnostics and targeted therapies.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39319421

RESUMO

Photothermal therapy (PTT) encounters challenges of rapid thermal loss and potential tissue damage. In response, we propose a Heat-Boost and Lock implant coating strategy inspired by the thermal adaptation of biological membranes, enabling precise local photothermal utilization. This coating incorporates a poly(tannic acid) (pTA) bridging layer on implants, facilitating stable layer-by-layer integration of a black phosphorus (BP) photothermal layer and a top cell membrane Heat-Boost and Lock layer. The cell membrane layer significantly curtails photothermal loss (extending the heat retention by 17.62%) and stores energy within its phospholipid bilayer, boosting photothermal effects near implants (achieving a temperature increasement of 275%). Theoretical analysis indicates that these local heat preservation properties of the cell membrane arise from its low thermal conductivity and phase-change properties. In a Staphylococcus aureus-infected bone implant model, our coating demonstrates precise antibacterial action around implants (reach an antibacterial ratio of 99.52%). The synergetic locking function of cell membrane and pTA delays BP biodegradation, ensuring favorable photothermal stability and long-term osteo-inductive performance (increasing the bone volume fraction by 53.45%). Beyond providing an endogenic biointerface, this strategy extends the application of cell membrane in local thermal management, offering possibilities for effective and safe PTT modalities.

3.
Adv Mater ; : e2405953, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101293

RESUMO

Implant-associated infections (IAIs) are the main cause of prosthetic implant failure. Bacterial biofilms prevent antibiotic penetration, and the unique metabolic conditions in hypoxic biofilm microenvironment may limit the efficacy of conventional antibiotic treatment. Escaping survival bacteria may not be continually eradicated, resulting in the recurrence of IAIs. Herein, a sonosensitive metal-organic framework of Cu-TCPP (tetrakis(4-carboxyphenyl) porphyrin) nanosheets and tinidazole doped probiotic-derived membrane vesicles (OMVs) with high-penetration sonodynamic therapy (SDT), bacterial metabolic state interference, and bacterial cuproptosis-like death to eradicate IAIs is proposed. The Cu-TCPP can convert O2 to toxic 1O2 through SDT in the normoxic conditions, enhancing the hypoxic microenvironment and activating the antibacterial activity of tinidazole. The released Cu(II) under ultrasound can be converted to Cu(I) by exogenous poly(tannic acid) (pTA) and endogenous glutathione. The disruption of the bacterial membrane by SDT can enhance the Cu(I) transporter activity. Transcriptomics indicate that the SDT-enhanced Cu(I) overload and hypoxia-activated therapy hinder the tricarboxylic acid cycle (TCA), leading to bacterial cuproptosis-like death. Moreover, the OMVs-activated therapy can polarize macrophages to a M2-like phenotype and facilitate bone repair. The sonodynamic biofilm microenvironment modulation strategy, whereby the hypoxia-enhanced microenvironment is potentiated to synergize SDT with OMVs-activated therapy, provides an effective strategy for antibacterial and osteogenesis performance.

4.
Mater Horiz ; 11(19): 4651-4664, 2024 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-38990315

RESUMO

Photothermal therapy (PTT) encounters challenges in addressing deep tissue infections, characterized by limited penetration or potential hyperthermal damage to surrounding tissues, initiating undesirable inflammatory cascades. Inspired by polar bear thermal regulation, we present a "bio-based endogenic thermal-adaptive booster" implant coating. This coating integrates a photothermal poly(tannic acid) (pTA) layer, mimicking the "polar bear dark skin", securely linked with anti-inflammatory dexamethasone (Dex), resembling the "secretion", and a red blood cell membrane (RBCM) layer, forming the insulating "transparent fur". The RBCM "fur" demonstrates unexpectedly superior local heat storage, amplifying the photothermal effect of the pTA "skin" by 1.30 times and boosting localized photothermal antibacterial efficiency by 1.30-fold (approximately 99%) compared to those without RBCM. Furthermore, RBCM sustains Dex release and offers additional protection against thermal inflammation, releasing Dex 1.90 times more under NIR irradiation than under non-photothermal conditions. In a rat infectious bone model, the photothermal-boosting implant coating provides a favorable biological interface and achieves a 99.97% photothermal antibacterial ratio, enhancing osseointegration without evident tissue harm, evidenced by a 2.47-fold increase in bone volume fraction and a 2.24-fold reduction in pro-inflammatory cytokines compared to those lacking a RBCM. Insights derived from cell membrane-based thermal-adaptive coatings herald a paradigm shift in efficient and safe PTT.


Assuntos
Dexametasona , Terapia Fototérmica , Animais , Ratos , Terapia Fototérmica/métodos , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Antibacterianos/farmacologia , Pele/efeitos dos fármacos , Pele/patologia , Próteses e Implantes , Anti-Inflamatórios/farmacologia
5.
ACS Appl Mater Interfaces ; 16(6): 7883-7893, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38299449

RESUMO

Effective heat dissipation and real-time temperature monitoring are crucial for ensuring the long-term stable operation of modern, high-performance electronic products. This study proposes a silicon rubber polydimethylsiloxane (PDMS)-based nanocomposite with a rapid thermal response and high thermal conductivity. This nanocomposite enables both rapid heat dissipation and real-time temperature monitoring for high-performance electronic products. The reported material primarily consists of a thermally conductive layer (Al2O3/PDMS composites) and a reversible thermochromic layer (organic thermochromic material, graphene oxide, and PDMS nanocoating; OTM-GO/PDMS). The thermal conductivity of OTM-GO/Al2O3/PDMS nanocomposites reached 4.14 W m-1 K-1, reflecting an increase of 2200% relative to that of pure PDMS. When the operating temperature reached 35, 45, and 65 °C, the surface of OTM-GO/Al2O3/PDMS nanocomposites turned green, yellow, and red, respectively, and the thermal response time was only 30 s. The OTM-GO/Al2O3/PDMS nanocomposites also exhibited outstanding repeatability and maintained excellent color stability over 20 repeated applications.

6.
J Mater Chem B ; 12(4): 842-871, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38173410

RESUMO

Infectious bone defects are characterized by the partial loss or destruction of bone tissue resulting from bacterial contaminations subsequent to diseases or external injuries. Traditional bone transplantation and clinical methods are insufficient in meeting the treatment demands for such diseases. As a result, researchers have increasingly focused on the development of more sophisticated biomaterials for improved therapeutic outcomes in recent years. This review endeavors to investigate specific reparative materials utilized for the treatment of infectious bone defects, particularly those present in the maxillofacial region, with a focus on biomaterials capable of releasing therapeutic substances, functional contact biomaterials, and novel physical therapy materials. These biomaterials operate via heightened antibacterial or osteogenic properties in order to eliminate bacteria and/or stimulate bone cells regeneration in the defect, ultimately fostering the reconstitution of maxillofacial bone tissue. Based upon some successful applications of new concept materials in bone repair of other parts, we also explore their future prospects and potential uses in maxillofacial bone repair later in this review. We highlight that the exploration of advanced biomaterials holds promise in establishing a solid foundation for the development of more biocompatible, effective, and personalized treatments for reconstructing infectious maxillofacial defects.


Assuntos
Materiais Biocompatíveis , Osteogênese , Materiais Biocompatíveis/uso terapêutico , Regeneração Óssea , Osso e Ossos
7.
Oncogene ; 43(2): 136-150, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37973951

RESUMO

Impaired macroautophagy/autophagy flux has been implicated in the treatment of prostate cancer (PCa). However, the mechanism underlying autophagy dysregulation in PCa remains unknown. In the current study, we investigated the role of diacylglycerol acyltransferases 1 (DGAT1) and its potential effects on cellular energy homeostasis and autophagy flux in PCa. The results of immunohistochemical staining suggested that DGAT1 expression was positively corrected with tumor stage and node metastasis, indicating DGAT1 is an important factor involved in the development and progression of PCa. Furthermore, targeting DGAT1 remarkably inhibited cell proliferation in vitro and suppressed PCa growth in xenograft models by triggering severe oxidative stress and subsequently autophagy flux blockage. Mechanically, DGAT1 promoted PCa progression by maintaining cellular energy homeostasis, preserving mitochondrial function, protecting against reactive oxygen species, and subsequently promoting autophagy flux via regulating lipid droplet formation. Moreover, we found that fenofibrate exhibits as an upstream regulator of DGAT1. Fenofibrate performed its anti-PCa effect involved the aforementioned mechanisms, and partially dependent on the regulation of DGAT1. Collectively. These findings indicate that DGAT1 regulates PCa lipid droplets formation and is essential for PCa progression. Targeting DGAT1 might be a promising method to control the development and progression of PCa. Schematic representation of DGAT1 affects autophagy flux by regulating lipid homeostasis and maintaining mitochondrial function in prostate cancer (PCa). PCa is characterized up-regulation of DGAT1, leading to the translocation of free fatty acids into lipid droplets, thereby preventing PCa cell from lipotoxicity. Inhibition of DGAT1 suppresses growth of PCa by inducing oxidative stress and subsequently autophagy flux blockage. Further, the current results revealed that fenofibrate exhibits as an upstream regulator of DGAT1, and fenofibrate plays an anti-PCa role partially dependent on the regulation of DGAT1, suggesting a potential therapeutic approach to ameliorate this refractory tumor.


Assuntos
Fenofibrato , Neoplasias da Próstata , Humanos , Masculino , Autofagia , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Fenofibrato/metabolismo , Fenofibrato/farmacologia , Fenofibrato/uso terapêutico , Estresse Oxidativo , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo
8.
Front Endocrinol (Lausanne) ; 14: 1250033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053725

RESUMO

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The disease originates from the cortex of adrenal gland and lacks effective treatment. Efforts have been made to elucidate the pathogenesis of ACC, but the molecular mechanisms remain elusive. To identify key genes and pathways in ACC, the expression profiles of GSE12368, GSE90713 and GSE143383 were downloaded from the Gene Expression Omnibus (GEO) database. After screening differentially expressed genes (DEGs) in each microarray dataset on the basis of cut-off, we identified 206 DEGs, consisting of 72 up-regulated and 134 down-regulated genes in three datasets. Function enrichment analyses of DEGs were performed by DAVID online database and the results revealed that the DEGs were mainly enriched in cell cycle, cell cycle process, mitotic cell cycle, response to oxygen-containing compound, progesterone-mediated oocyte maturation, p53 signaling pathway. The STRING database was used to construct the protein-protein interaction (PPI) network, and modules analysis was performed using Cytoscape. Finally, we filtered out eight hub genes, including CDK1, CCNA2, CCNB1, TOP2A, MAD2L1, BIRC5, BUB1 and AURKA. Biological process analysis showed that these hub genes were significantly enriched in nuclear division, mitosis, M phase of mitotic cell cycle and cell cycle process. Violin plot, Kaplan-Meier curve and stage plot of these hub genes confirmed the reliability of the results. In conclusion, the results in this study provided reliable key genes and pathways for ACC, which will be useful for ACC mechanisms, diagnosis and candidate targeted treatment.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Perfilação da Expressão Gênica/métodos , Carcinoma Adrenocortical/genética , Redes Reguladoras de Genes , Reprodutibilidade dos Testes , Neoplasias do Córtex Suprarrenal/genética , Biologia Computacional/métodos
9.
Foods ; 12(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38137188

RESUMO

Deltamethrin, an important pyrethroid insecticide, is frequently detected in human samples. This study aims to assess the potential effects of deltamethrin on human health and investigate the patterns of residue enrichment and elimination in 112 healthy laying hens. These hens were administered 20 mg·kg-1 deltamethrin based on their body weight. Gas chromatography-mass spectrometry (GC-MS) was used to investigate the residue enrichment pattern and elimination pattern of deltamethrin in the hens. The results indicated a significant increase in the concentration of deltamethrin in chicken manure during the treatment period. By the 14th day of administration, the concentration of deltamethrin in the stool reached 13,510.9 ± 172.24 µg·kg-1, with a fecal excretion rate of 67.56%. The pulmonary deltamethrin concentration was the second highest at 3844.98 ± 297.14 µg·kg-1. These findings suggest that chicken feces contain substantial amounts of deltamethrin after 14 days of continuous administration, and that it can easily transfer to the lungs. After 21 days of drug withdrawal, the residual concentration of deltamethrin in the fat of laying hens was 904.25 ± 295.32 µg·kg-1, with a half-life of 17 days and a slow elimination rate. In contrast, the lungs showed relatively low elimination half-lives of 0.2083 days, indicating faster elimination of deltamethrin in this tissue. These results highlight differences in the rate of deltamethrin elimination in different tissues during drug withdrawal. The fat of laying hens exhibited the highest residue of deltamethrin and the slowest elimination rate, while the lungs showed the fastest elimination rate. Moreover, deltamethrin was found to accumulate in the edible tissues of eggs and laying hens, suggesting that humans may be exposed to deltamethrin through food.

10.
Environ Sci Pollut Res Int ; 30(52): 112385-112396, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37831236

RESUMO

The utilization of phosphate-solubilizing bacteria (PSB) in agriculture has long been proposed as an eco-friendly method to enhance soil phosphorus (P) availability, thereby reducing reliance on chemical P fertilizers. However, their application in saline soils is challenged by salt-induced stress on common PSB strains. In this study, we sourced bacterial strains from marine environments, aiming to identify robust PSB strains adaptable to saline conditions and assess their potential as P bio-fertilizers through a microcosm experiment. Our findings indicate that the inoculation of a selected marine PSB, Bacillus paramycoides 3-1a, increased soil available P content by 12.5% when applied alone and by 61.2% when combined with organic amendments. This enhancement results from improved inorganic P solubilization and organic P mineralization in soils. Additionally, these treatments raised soil nitrogen levels, reshaped microbial community structures, and significantly enhanced wheat (Triticum aestivum L.) growth, with P accumulation increasing by 24.2-40.9%. Our results underscore the potential of marine PSB in conjunction with organic amendments for the amelioration of saline agricultural soils.


Assuntos
Fósforo , Solo , Solo/química , Fertilizantes , Bactérias , Fosfatos , Triticum
11.
Medicine (Baltimore) ; 102(37): e34917, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713902

RESUMO

BACKGROUND: Mindfulness-based stress reduction (MBSR) has been suggested as an effective mind-body approach for relieving stress in patients with chronic diseases. As of yet, there is no conclusive research on MBSR's role in reducing affective disorders among cancer patients. A systematic review and meta-analysis was conducted to determine whether MBSR has an impact on loneliness, anxiety, and depression in cancer patients. METHODS: Systematic searches were conducted in PubMed, Embase, and the Cochrane Library from the start of these databases to January 2nd, 2022 to identify relevant randomized controlled trials. Two authors independently conducted the literature search, collected the data, and performed the statistical analysis. In order to account for potential between-study heterogeneity, a random-effect model was used in the meta-analysis. RESULTS: The meta-analysis included 16 studies with 2072 cancer patients. Among the 16 studies, 13 included patients with breast cancer, and the follow-up duration ranged from 6 to 53 weeks. Compared to controls receiving standard cancer care, interventions of MBSR with sessions for 6 to 8 weeks significantly improved loneliness (standard mean difference [SMD]: -0.35, 95% confidence interval [CI]: -0.59 to -0.12, P = .003, I2 = 46%), anxiety (SMD: -0.51, 95% CI: -0.73 to -0.30, P < .001, I2 = 77%), and depression (SMD: -0.61, 95% CI: -1.02 to -0.20, P = .004, I2 = 94%) in patients with cancer. CONCLUSION: According to recent research, MBSR may be beneficial to patients diagnosed with cancer who are feeling lonely, anxious, or depressed.


Assuntos
Neoplasias da Mama , Atenção Plena , Humanos , Feminino , Solidão , Depressão/etiologia , Depressão/terapia , Ansiedade/etiologia , Ansiedade/terapia
12.
J Diabetes ; 15(9): 736-752, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37442561

RESUMO

Obesity and type 2 diabetes(T2D) lead to defects in intestinal hormones secretion, abnormalities in the composition of bile acids (BAs), increased systemic and adipose tissue inflammation, defects of branched-chain amino acids (BCAAs) catabolism, and dysbiosis of gut microbiota. Bariatric surgery (BS) has been shown to be highly effective in the treatment of obesity and T2D, which allows us to view BS not simply as weight-loss surgery but as a means of alleviating obesity and its comorbidities, especially T2D. In recent years, accumulating studies have focused on the mechanisms of BS to find out which metabolic parameters are affected by BS through which pathways, such as which hormones and inflammatory processes are altered. The literatures are saturated with the role of intestinal hormones and the gut-brain axis formed by their interaction with neural networks in the remission of obesity and T2D following BS. In addition, BAs, gut microbiota and other factors are also involved in these benefits after BS. The interaction of these factors makes the mechanisms of metabolic improvement induced by BS more complicated. To date, we do not fully understand the exact mechanisms of the metabolic alterations induced by BS and its impact on the disease process of T2D itself. This review summarizes the changes of intestinal hormones, BAs, BCAAs, gut microbiota, signaling proteins, growth differentiation factor 15, exosomes, adipose tissue, brain function, and food preferences after BS, so as to fully understand the actual working mechanisms of BS and provide nonsurgical therapeutic strategies for obesity and T2D.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Hormônios Gastrointestinais , Humanos , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Obesidade/cirurgia , Obesidade/metabolismo , Redução de Peso
13.
Front Bioeng Biotechnol ; 11: 1158672, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37214290

RESUMO

The CRISPR (Clustered Regularly Spaced Short Palindromic Repeats) system was first discovered in prokaryotes as a unique immune mechanism to clear foreign nucleic acids. It has been rapidly and extensively used in basic and applied research owing to its strong ability of gene editing, regulation and detection in eukaryotes. Hererin in this article, we reviewed the biology, mechanisms and relevance of CRISPR-Cas technology and its applications in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. CRISPR-Cas nucleic acid detection tools include CRISPR-Cas9, CRISPR-Cas12, CRISPR-Cas13, CRISPR-Cas14, CRISPR nucleic acid amplification detection technology, and CRISPR colorimetric readout detection system. The above CRISPR technologies have been applied to the nucleic acid detection, including SARS-CoV-2 detection. Common nucleic acid detection based on CRISPR derivation technology include SHERLOCK, DETECTR, and STOPCovid. CRISPR-Cas biosensing technology has been widely applied to point-of-care testing (POCT) by targeting recognition of both DNA molecules and RNA Molecules.

14.
Metabolites ; 13(4)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37110151

RESUMO

As set in the maximum residue limit regulations of the European Commission, this study aimed to obtain the residual parameters in milk with optimized UPLC-MS/MS conditions and to determine the conclusive drug withdrawal period to ensure food safety. In this research, an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to study cefquinome sulfate's residue elimination in milk and to calculate cefquinome's withdrawal period. Twelve healthy cows free of endometritis were selected for the experiment. Before using the drug, the vaginal orifice and perineum of each cow was disinfected. One dose of intrauterine perfusion was used for each cow, followed by an additional dose after 72 h. Before administration and 12 h, 18 h, 24 h, 36 h, 42 h, 48 h, 60 h, 66 h, 72 h, 84 h, 90 h, and 96 h after the last dose, milk (10 mL) was gathered from each cow's teat and pooled. For the measurement of cefquinome concentrations in milk, UPLC-MS/MS was performed. A calibration curve was generated using linear regression as follows: Y = 250.86X - 102.29, with a correlation coefficient of 0.9996; the limits of detection and the limits of quantitation were 0.1 µg·kg-1 and 0.2 µg·kg-1, respectively. The average recovery of cefquinome was 88.60 ± 16.33% at 0.2 µg·kg-1, 100.95 ± 2.54% at 10 µg·kg-1, and 97.29 ± 1.77% at 50 µg·kg-1. For 5 consecutive days at the three spiking levels, the intra and inter-day relative standard deviations (RSD) were 1.28%-13.73% and 1.81%-18.44%, respectively; the residual amount of cefquinome was less than the maximum residue limit of 20 µg·kg-1, 36 h after administration; and the residual amount was less than the limit of detection (0.1 µg·kg-1) 48 h after administration. The withdrawal time of cefquinome in cow's milk was 39.8 h, as calculated using WTM1.4 software. In terms of clinical practical use, the withdrawal period of milk was temporarily set at 48 h after the administration of the cefquinome sulfate uterus injection to cows, in accordance with the recommended dose and course.

15.
Nat Commun ; 14(1): 1621, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36959224

RESUMO

X-ray detectors must be operated at minimal doses to reduce radiation health risks during X-ray security examination or medical inspection, therefore requiring high sensitivity and low detection limits. Although organolead trihalide perovskites have rapidly emerged as promising candidates for X-ray detection due to their low cost and remarkable performance, these materials threaten the safety of the human body and environment due to the presence of lead. Here we present the realization of highly sensitive X-ray detectors based on an environmentally friendly solution-grown thick BiI/BiI3/BiI (BixIy) van der Waals heterostructure. The devices exhibit anisotropic X-ray detection response with a sensitivity up to 4.3 × 104 µC Gy-1 cm-2 and a detection limit as low as 34 nGy s-1. At the same time, our BixIy detectors demonstrate high environmental and hard radiation stabilities. Our work motivates the search for new van der Waals heterostructure classes to realize high-performance X-ray detectors and other optoelectronic devices without employing toxic elements.

16.
BMC Vet Res ; 19(1): 19, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681807

RESUMO

Escherichia coli (E. coli) is an opportunistic pathogen that can cause clinical mastitis in dairy cows worldwide. Mastitis produces severe symptoms in dairy cows, such as udder inflammation, the production of harmful substances, reduced milk production, and altered milk quality. Intramammary injections of rifaximin have a beneficial effect on dairy cow mastitis, especially for mastitis caused by E. coli. However, we do not know whether the currently accepted clinical administration scheme is reasonable. Therefore, the purpose of this experiment was to evaluate the clinical dosing regimen for curing mastitis induced by E. coli. In this study, the pharmacokinetics of four single dose groups (50, 100, 200, and 400 µg/gland) were studied in CD-1 lactating mice, and the main pharmacokinetic parameters were obtained by non-compartment and two-compartment model of Phoenix 8.1 software. A total of 5,000 colony-forming units (CFU) of E. coli ATCC25922 were injected into the mammary glands of mice under anatomic microscope guidance. After 12 h of growth in vivo, the mouse mastitis model was successfully developed. In pharmacodynamics experiment, 12 different dosing regimens (doses ranged from 25 to 800 µg/gland and two dosing intervals of 12 and 24 h) were used to study the therapeutic potential of rifaximin for mastitis. The PK/PD model was established by integrating pharmacokinetics and pharmacodynamics using the inhibitory sigmoid Emax model. The optimal antibacterial effect was 2log10CFU/gland reduction of bacterial colony counts in vivo, when the magnitude of AUC24/MIC exceeded 57.80 h. A total of 57.80 h of AUC24/MIC was defined as a target value in the Monte Carlo simulation. The clinically recommended dosage regimen of 100 mg/gland every 12 h in a day achieved a 91.08% cure rate for the treatment of bovine mastitis caused by E. coli infection.


Assuntos
Doenças dos Bovinos , Infecções por Escherichia coli , Mastite Bovina , Feminino , Bovinos , Animais , Camundongos , Escherichia coli , Rifaximina/uso terapêutico , Lactação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/veterinária , Leite/microbiologia , Mastite Bovina/tratamento farmacológico , Mastite Bovina/microbiologia , Glândulas Mamárias Animais
17.
Am J Physiol Endocrinol Metab ; 324(1): E24-E41, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36383637

RESUMO

The prevalence of obesity has increased dramatically during the past decades, which has been a major health problem. Since 1975, the number of people with obesity worldwide has nearly tripled. An increasing number of studies find obesity as a driver of chronic kidney disease (CKD) progression, and the mechanisms are complex and include hemodynamic changes, inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system (RAAS). Obesity-related kidney disease is characterized by glomerulomegaly, which is often accompanied by localized and segmental glomerulosclerosis lesions. In these patients, the early symptoms are atypical, with microproteinuria being the main clinical manifestation and nephrotic syndrome being rare. Weight loss and RAAS blockers have a protective effect on obesity-related CKD, but even so, a significant proportion of patients eventually progress to end-stage renal disease despite treatment. Thus, it is critical to comprehend the mechanisms underlying obesity-related CKD to create new tactics for slowing or stopping disease progression. In this review, we summarize current knowledge on the mechanisms of obesity-related kidney disease, its pathological changes, and future perspectives on its treatment.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefropatias , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/complicações , Obesidade/complicações , Sistema Renina-Angiotensina/fisiologia , Glomerulosclerose Segmentar e Focal/complicações , Doença Crônica , Rim , Progressão da Doença
18.
Front Vet Sci ; 9: 1079580, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36570503

RESUMO

Pyrethroid pesticides, with low toxicity to birds and mammals and short persistence in the environment, are widely used now. With the development of intensive poultry farming, pesticide application leads to residues in poultry products and pollution in ecological environment. The aim of the present study was to examine deltamethrin subchronic toxicity in laying chickens. One hundred and twelve laying chickens were randomly assigned to 14 groups including 13 groups medicated with deltamethrin (n = 8) and one unmedicated group used as control (n = 8). Tissue samples were collected during and after administration for weighing and histopathological analysis. A single dose of deltamethrin (20 mg·kg-1·BW·d) was administered orally to laying chickens for 14 days. The results showed that deltamethrin has no significant effect on the relative organ weight of laying chickens (p > 0.05). The activities of aspartate aminotransferase and cholinesterase in the plasma gradually decreased over time in the medicated group (p < 0.05). Plasma concentrations of urea nitrogen, uric acid, cholesterol, triglycerides, and creatinine significantly increased during treatment (p < 0.05), and significant liver damage and loss of intestinal villous epithelium were observed. The intestinal wall thickness, villus height, and crypt depth of laying chickens were altered by deltamethrin treatment. During treatment was withdrawn, the intestinal repair was more extensive than the liver repair.

19.
Front Endocrinol (Lausanne) ; 13: 984593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313770

RESUMO

Background: The correlation between benign thyroid disease (BTD) and breast cancer (BC) has long been discussed. However, the definite relationship and potential mechanism between them are still disputed. The current meta-analysis aimed at performing a comprehensive assessment of the relationship between different types of benign thyroid disease and the risk of breast cancer, furthermore, assessing whether benign thyroid disease exerts an influence on the aggressiveness of breast cancer. Method: A systematic literature search (PubMed, Web of Science, MEDLINE, and Embase databases) identified studies to evaluate the correlation between BTD and BC risk. Data were analyzed using version 16.0 STATA software, including the odds ratio (OR) and its corresponding 95% confidence intervals (CIs). Publication bias and quality assessment were conducted for the included studies. Result: Overall, 18 studies involving 422,384 patients with BTD were incorporated. The outcome showed that autoimmune thyroiditis (OR: 2.56, 95%CI: 1.95-3.37, I2 = 0.0%, p=0.460), goiter (OR: 2.13, 95%CI: 1.19-3.79, I2 = 80.6%, p=0.000), and Graves' disease (OR: 5.01, 95%CI: 1.49-16.82, I2 = 0.0%, p=0.358) was connected with a higher risk of BC. Both hypothyroidism (OR: 0.82, 95%CI: 0.64-1.04, I2 = 85.0%, p=0.000) and hyperthyroidism (OR: 1.07, 95%CI: 0.93-1.24, I2 = 24.9%, p=0.206) had no significant association with the risk of BC. Additionally, the pooled analysis showed no apparent correlation between BTD and aggressiveness of BC. However, subgroup analysis indicated a positive relationship between BTD and aggressiveness of BC in the Europe subgroup (HR: 2.05, 95%CI: 1.32-3.17, I2 = 86.4%, p=0.000). Conclusion: Autoimmune thyroiditis, goiter, and Graves' disease are connected with an increased risk of BC. Furthermore, subgroup analysis suggested that BTD increases the aggressiveness of BC in the European population geographically. Nevertheless, further research is needed to prove these discoveries.


Assuntos
Neoplasias da Mama , Bócio , Doença de Graves , Doenças da Glândula Tireoide , Tireoidite Autoimune , Humanos , Feminino , Tireoidite Autoimune/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , Bócio/complicações , Doença de Graves/complicações
20.
J Food Biochem ; 46(12): e14490, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36288503

RESUMO

In this study, the Chinese yam peel polysaccharide (CYPP) was obtained under the extraction conditions optimized by the Response Surface Methodology (RSM). Further biological properties of CYPP-1 purified from CYPP were also determined. The results indicated that the optimum extraction conditions were an extraction temperature of 90.5°C, a liquid-solid ratio of 28.0 ml/g, and an extraction time of 2.94 h, along with a yield of 8.81 ± 1.48%. CYPP-1 was identified as a kind of heteropolysaccharide mostly composed of glucose and galactose (59.4:1.0). The molecular weights were two main parts of 50.5 kDa (54.77%) and 4.4 kDa (21.02%), and the triple-helix conformation was not formed in CYPP-1. Besides, CYPP-1 showed good biological properties including in vitro antioxidant activity and immunomodulatory function on RAW264.7 cells, as well as favorable hypoglycemic effect. Overall, the high-value utilization of CYPP-1 reveals a broad application prospect in the industrial production of functional foods and pharmaceuticals. PRACTICAL APPLICATIONS: Yam peel, which is discarded in large quantities during postharvest processing, results in the production of tremendous by-products and is a great waste of resources. In this study, the yield of water-soluble polysaccharide from yam peel reached 8.81 ± 1.48%. Besides, the purified CYPP-1 exhibited excellent antioxidant activity, favorable immunomodulatory function, and hypoglycemic effect. The high productivity and bioactive effects are both great merits for Chinese yam peel polysaccharide as a promising candidate for foods and medicines industrial production.


Assuntos
Dioscorea , Dioscorea/química , Antioxidantes/farmacologia , Polissacarídeos/química , Glucose , Hipoglicemiantes
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