RESUMO
Introduction: Kinesiophobia denotes an excessive and irrational apprehension towards physical activity or exercise among patients, stemming from a perception of susceptibility to painful injury or re-injury. Cardiac rehabilitation stands pivotal in the secondary prevention spectrum for individuals with cardiovascular ailments, with exercise constituting a cornerstone of this regimen. However, the emergence of kinesiophobia poses a formidable challenge, diminishing patient adherence to cardiac rehabilitation protocols, particularly among those grappling with chronic heart failure. To bolster exercise-based rehabilitation initiatives in this cohort, a thorough comprehension of the multifaceted factors precipitating kinesiophobia is imperative. This review endeavors to delineate prevailing evidence and prevalence concerning kinesiophobia triggers in chronic heart failure patients, while pinpointing research lacunae for future exploration. Methods: Employing a scoping review methodology, our investigation culled data from diverse scholarly databases, including Embase, PubMed, Scopus, CINAHL, Web of Science, Medline, Sinomed, CNKI, Wangfan, and VIP. Results: After thorough evaluation, 9 studies that met the inclusion criteria were ultimately incorporated. Discussion: Our findings underscore a notable prevalence of kinesiophobia in chronic heart failure patients, predominantly influenced by socio-demographic factors, psychological and cognitive factors, disease and treatment factors, as well as lifestyle and behavior. Armed with these insights, future interventions can be tailored to mitigate kinesiophobia levels, fostering enhanced engagement in exercise-centric cardiac rehabilitation endeavors among patients grappling with chronic heart failure.
RESUMO
The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.
Assuntos
Hidrocefalia , Humanos , Hidrocefalia/genética , Hidrocefalia/etiologia , Animais , Predisposição Genética para DoençaRESUMO
The emergence of carbapenem-resistant bacteria especially carbapenem-resistant Escherichia coli (CREC) in food animals poses a serious threat to food safety and public health. Reports about the dissemination of carbapenem-resistant bacteria along the food animal production chain are scattered and mainly focus on swine and chicken. Abuse of antibiotics in duck farms is common especially in China which has the largest duck production industry, however, the CREC transmission between farmed ducks and slaughtered meats remains unclear and the role of slaughterhouse in disseminating CREC among duck meats remains largely unknown. Herein, we collected 251 fecal samples from five typical duck farms along with 125 slaughtered meat samples (25 from each farm) in the corresponding slaughterhouse in Anhui Province, China, in December 2018. All samples were screened for CREC isolates which were analyzed for the presence of carbapenemase genes and colistin resistance gene mcr. The resistance profiles, transferability, pulsed-field gel electrophoresis (PFGE), whole-genome sequencing and phylogenetic analysis of the CREC isolates from both ducks and meats were further characterized. This is the first report presenting the high prevalence of blaNDM-positive CREC isolates in ducks from duck farms (57.8 %) and slaughtered meats (33.6 %) in the corresponding slaughterhouse. Among the 203 blaNDM-positive CREC isolates obtained in this study, 19.2 % harbored mcr-1 and all CREC isolates showed resistance to nearly all currently available antibiotics (except tigecycline). Of note, mcr-1 was found in 17.8 % of the meat-derived CREC carrying blaNDM. Based on the PFGE analysis, clonal spread of blaNDM-positive CREC including some also carrying mcr-1 was found between farmed ducks and slaughtered duck meats even from different farms. Special attention should be paid to the clonal dissemination of meat-derived CREC within the slaughterhouse, which contributed to the high prevalence of blaNDM in slaughtered meats. Additionally, horizontal transmission mainly mediated by transferable blaNDM-5-bearing IncX3 plasmids, untypable blaNDM-1-bearing plasmids and mcr-1-bearing IncHI2 plasmids further facilitated the rapid spread of such multidrug-resistant strains. Notably, the blaNDM-bearing plasmids and mcr-1-bearing plasmids in CREC from meats were highly similar to those from animals and humans. More worryingly, the phylogenomic analysis showed that CREC isolates from both ducks and corresponding meats clustered with previously reported human CREC isolates carrying mcr-1 in different geographical areas including China. These findings further prove that the CREC and resistance plasmids in farmed ducks could transmit to meats even from different farms via the slaughterhouse and then trigger infections in humans. The high prevalence and clonal transmission of CREC isolates including those also carrying mcr-1 between ducks and meats are alarming, and urgent control measures are required to reduce the dissemination of such organisms.
RESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) infertility has attracted great attention from researchers due to its high incidence. Numerous studies have shown that Chinese medicine is effective in treating this disease, but there is a wide variety of Chinese medicine therapies available, and there is a lack of comparative evaluation of the efficacy of various Chinese medicine combination therapies in the clinic, which requires further in-depth exploration. This study aims to evaluate the efficacy of a combined traditional Chinese medicine (TCM) therapy for the treatment of infertility with PCOS using network meta-analysis (NMA). METHODS: In PubMed, web of Science, Cochrane Library, Embase, China Knowledge Network, Wanfang Data, VIP Database, China Biomedical Literature Database (SinoMed) databases, searchs were conducted for information about the randomized controlled trials (RCTs) of combined TCM therapy for the treatment of infertility with PCOS. Quality evaluation was performed using the Cochrane 5.3 risk of bias assessment tool, and NMA using Stata 16.0. RESULTS: This study comprised 28 RCTs using 8 combined TCM therapies in total. The results of the NMA showed that moxibustionâ +â herbal, fire acupunctureâ +â herbal, acupunctureâ +â herbal, electroacupunctureâ +â herbal, and acupoint applicationâ +â herbal improved the clinical pregnancy rate better than acupuncture, herbal, and western medicines monotherapy (Pâ <â .05). Additionally, ear point pressureâ +â herbal enemaâ +â herbal, acupuncture and moxibustionâ +â herbal, fire acupunctureâ +â herbal, and acupunctureâ +â herbal improved the ovulation rate better than acupuncture, herbal, and western medicines monotherapy (Pâ <â .05). Moxibustionâ +â herbal, fire acupunctureâ +â herbal, and acupunctureâ +â herbal are the 3 most effective therapies for improving the clinical pregnancy rate. Fire acupunctureâ +â herbal, acupunctureâ +â herbal, and ear point pressureâ +â herbal enemaâ +â herbal are the 3 most effective therapies for improving the ovulation rate. CONCLUSION: The combined TCM therapy demonstrated better efficacy for the treatment of infertility with PCOS compared to acupuncture, herbal, and western medicines monotherapy. However, the optimal treatment therapy varied depending on the outcome indicators. Further large sample, high-quality, and standardized RCTs are needed to verify these findings.
Assuntos
Infertilidade Feminina , Medicina Tradicional Chinesa , Síndrome do Ovário Policístico , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Infertilidade Feminina/terapia , Infertilidade Feminina/etiologia , Infertilidade Feminina/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Terapia Combinada , Metanálise em Rede , Gravidez , Terapia por Acupuntura/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Taxa de GravidezRESUMO
The development of an artificial ligament with a multifunction of promoting bone formation, inhibiting bone resorption, and preventing infection to obtain ligament-bone healing for anterior cruciate ligament (ACL) reconstruction still faces enormous challenges. Herein, a novel artificial ligament based on a PI fiber woven fabric (PIF) was fabricated, which was coated with a phytic acid-gallium (PA-Ga) network via a layer-by-layer assembly method (PFPG). Compared with PIF, PFPG with PA-Ga coating significantly suppressed osteoclastic differentiation, while it boosted osteoblastic differentiation in vitro. Moreover, PFPG obviously inhibited fibrous encapsulation and bone absorption while accelerating new bone regeneration for ligament-bone healing in vivo. PFPG remarkably killed bacteria and destroyed biofilm, exhibiting excellent antibacterial properties in vitro as well as anti-infection ability in vivo, which were ascribed to the release of Ga ions from the PA-Ga coating. The cooperative effect of the surface characteristics (e.g., hydrophilicity/surface energy and protein absorption) and sustained release of Ga ions for PFPG significantly enhanced osteogenesis while inhibiting osteoclastogenesis, thereby achieving ligament-bone integration as well as resistance to infection. In summary, PFPG remarkably facilitated osteoblastic differentiation, while it suppressed osteoclastic differentiation, thereby inhibiting osteoclastogenesis for bone absorption while accelerating osteogenesis for ligament-bone healing. As a novel artificial ligament, PFPG represented an appealing option for graft selection in ACL reconstruction and displayed considerable promise for application in clinics.
Assuntos
Osteogênese , Ácido Fítico , Animais , Ácido Fítico/química , Ácido Fítico/farmacologia , Camundongos , Osteogênese/efeitos dos fármacos , Ligamentos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Regeneração Óssea/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologiaRESUMO
This study investigated the impact of multi-frequency ultrasound-assisted (20/28/40 kHz) thawing (MUAT) at different power levels (195, 220, 245, and 270 W, respectively) on the flesh quality and protein stability of large yellow croakers. Compared with flowing water thawing (FWT) and the other MUAT sample, flesh quality results indicated that the MUAT-220 W significantly reduced (p < 0.05) thawing loss, total volatile base nitrogen (TVB-N), total free amino acids (FAAs) and thiobarbituric acid reactive substances (TBARS). Low-field nuclear magnetic resonance (LF-NMR) spectroscopy indicated that MUAT-220 W samples had higher immobilized water content and lower free water content. In addition, the MUAT-220 W sample contained higher sulfhydryl and lower carbonyl contents compared to the FWT sample. Secondary and tertiary structural results of myofibrillar proteins (MPs) showed that MUAT-220 W significantly reduced thawing damage to MPs. Therefore, MUAT-220 W improved the quality and protein stability of the large yellow croaker during the defrosting process.
RESUMO
The incidence of colorectal cancer (CRC) is closely linked to metabolic diseases. Accumulating evidence suggests the regulatory role of AMP-activated protein kinase (AMPK) in cancer metabolic reprogramming. In this study, wild-type and AMPK knockout mice were subjected to azoxymethane-induced and dextran sulfate sodium (AOM/DSS)-promoted colitis-associated CRC induction. A stable AMPK-deficient Caco-2 cell line was also established for the mechanistic studies. The data showed that AMPK deficiency accelerated CRC development, characterized by increased tumor number, tumor size, and hyperplasia in AOM/DSS-treated mice. The aggravated colorectal tumorigenesis resulting from AMPK ablation was associated with reduced α-ketoglutarate production and ten-eleven translocation hydroxylase 2 (TET2) transcription, correlated with the reduced mismatch repair protein mutL homolog 1 (MLH1) protein. Furthermore, in AMPK-deficient Caco-2 cells, the mRNA expression of mismatch repair and tumor suppressor genes, intracellular α-ketoglutarate, and the protein level of TET2 were also downregulated. AMPK deficiency also increased hypermethylation in the CpG islands of Mlh1 in both colonic tissues and Caco-2 cells. In conclusion, AMPK deficiency leads to reduced α-ketoglutarate concentration and elevates the suppressive epigenetic modifications of tumor suppressor genes in gut epithelial cells, thereby increasing the risk of colorectal tumorigenesis. Given the modifiable nature of AMPK activity, it holds promise as a prospective molecular target for the prevention and treatment of CRC.
Assuntos
Proteínas Quinases Ativadas por AMP , Azoximetano , Carcinogênese , Neoplasias Colorretais , Metilação de DNA , Dioxigenases , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Azoximetano/toxicidade , Azoximetano/efeitos adversos , Células CACO-2 , Carcinogênese/genética , Colite/induzido quimicamente , Colite/genética , Colite/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/etiologia , Sulfato de Dextrana/toxicidade , Dioxigenases/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Ácidos Cetoglutáricos/metabolismo , Camundongos Knockout , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismoRESUMO
AIMS: The survival of inoculated Escherichia coli on Fuji apples in Washington State orchards was studied, considering evaporative cooling, canopy location, year, and region, with the examination of sunlight exposure and inoculation levels in year 2. METHODS AND RESULTS: Rifampicin-resistant E. coli was applied to Fuji apples. Initial concentrations for the high-inoculation study were 7.4 ± 0.3 log10 CFU per apple and 3.4 ± 0.3 log10 CFU per apple for the low-inoculation study. Enumeration of E. coli was conducted at 0, 2, 10, 18, 34, 42, 58, 82, 106, and 154 h after inoculation. Results were analyzed using Tukey's honest significance difference test and a log-linear model. Log-linear, Weibull, and Biphasic models characterized E. coli die-off patterns for high and low inoculations. The application of evaporative overhead cooling water did not significantly influence E. coli survival on Fuji apples; inoculation level and sunlight exposure were significant factors in a log-linear model. E. coli decreased by 5.5 ± 1.3 and 3.3 ± 0.4 log10 CFU per apple for high and low inoculated apples, respectively, by 154 h. The Biphasic model best explained the die-off pattern for high and low-inoculated Fuji apples. CONCLUSIONS: Overhead evaporative cooling, a useful fruit quality practice, did not impact the survival of generic E. coli on Fuji apple surfaces. The significant impact of sunlight exposure and inoculation levels on die-off highlights the importance of ultraviolet radiation in risk reduction and the need for various inoculum concentrations in preharvest field studies.
RESUMO
H2A.Z, the most evolutionarily conserved variant of histone H2A, plays a pivotal role in chromatin remodeling and contributes significantly to gene transcription and genome stability. However, the role of H2A.Z in the silkworm (Bombyx mori) remains unclear. In this study, we cloned the BmH2A.Z from B. mori. The open reading frame of BmH2A.Z is 390 bp, encoding 129 amino acids, with a confirmed molecular weight of 13.4 kDa through prokaryotic expression analysis. Sequence analysis revealed that BmH2A.Z has a conserved H2A.Z domain and is closely related to the systemic evolution of other known H2A.Zs. The expression profile of BmH2A.Z at various developmental stages of the B. mori exhibited the highest expression level in the 1st instar, followed by the grain stage and the 2nd instar, and the lowest expression level in the moth. The highest transcript level of BmH2A.Z was observed in the head, with relatively lower levels detected in the blood than in the other tissues under consideration. In addition, the upregulation of BmH2A.Z resulted in the amplified expression of B. mori nucleopolyhedrovirus (BmNPV) genes, thus facilitating the proliferation of BmNPV. This study establishes a foundation for investigating the role of BmH2A.Z in B. mori and its participation in virus-host interactions.
Assuntos
Sequência de Aminoácidos , Bombyx , Clonagem Molecular , Histonas , Proteínas de Insetos , Animais , Bombyx/genética , Bombyx/metabolismo , Bombyx/virologia , Histonas/metabolismo , Histonas/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Larva/genética , Larva/metabolismo , Larva/crescimento & desenvolvimento , Filogenia , Nucleopoliedrovírus/genética , Alinhamento de SequênciaRESUMO
To further reveal the inhibition mechanism of carbon dioxide (CO2) on Shewanella putrefaciens (S. putrefaciens), influence on metabolic function was studied by biochemical and metabolomics analysis. Accordingly, reduction of intracellular pH (pHi), depolarization of cell membrane and accumulation of reactive oxygen species (ROS) indicated that CO2 changed the membrane permeability of S. putrefaciens. Besides, adenosine triphosphate (ATP), ATPase, nicotinamide adenine dinucleotide (NAD+/NADH) and ratios of NADH/NAD+ were detected, indicating a role of CO2 in repressing respiratory pathway and electron transport. According to metabolomics results, CO2 induced differential expressions of metabolites, disordered respiratory chain and weakened energy metabolism of S. putrefaciens. Inhibition of respiratory rate-limiting enzymes also revealed that electron transfer of respiratory chain was blocked, cell respiration was weakened, and thus energy supply was insufficient under CO2 stress. These results revealed that CO2 caused disruption of metabolic function, which might be the main cause of growth inhibition for S. putrefaciens.
RESUMO
In this study, large yellow croaker (Larimichthys crocea) was frozen using multi-frequency ultrasound-assisted freezing (MUIF) with different powers (160 W, 175 W, and 190 W, respectively) and stored at -18 °C for ten months. The effect of different ultrasound powers on the myofibrillar protein (MP) structures and lipid oxidation of large yellow croaker was investigated. The results showed that MUIF significantly slowed down the oxidation of MP by inhibiting carbonyl formation and maintaining high sulfhydryl contents. These treatments also held a high activity of Ca2+-ATPase in the MP. MUIF maintained a higher ratio of α-helix to ß-sheet during frozen storage, thereby protecting the secondary structure of the tissue and stabilizing the tertiary structure. In addition, MUIF inhibited the production of thiobarbituric acid reactive substances value and the loss of unsaturated fatty acid content, indicating that MUIF could better inhibit lipid oxidation of large yellow croaker during long-time frozen storage.
Assuntos
Congelamento , Oxirredução , Perciformes , Animais , Fatores de Tempo , Armazenamento de Alimentos , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Ondas Ultrassônicas , ATPases Transportadoras de Cálcio/metabolismoRESUMO
Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO2 shell would deplete glutathione (GSH) and produce Mn2+, while a large amount of H2O2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn2+, producing high toxic â¢OH. More importantly, the cascade reaction between GOX and MnO2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.
Assuntos
Ferroptose , Glucose Oxidase , Indóis , Compostos de Manganês , Nanopartículas , Óxidos , Terapia Fototérmica , Polímeros , Terapia Fototérmica/métodos , Compostos de Manganês/química , Animais , Humanos , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Indóis/química , Polímeros/química , Glucose Oxidase/metabolismo , Glucose Oxidase/administração & dosagem , Nanopartículas/química , Camundongos , Óxidos/química , Linhagem Celular Tumoral , Peróxido de Hidrogênio/metabolismo , Camundongos Endogâmicos BALB C , Terapia Combinada/métodos , Feminino , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Camundongos NusRESUMO
Transpiration is a significant part of water cycle in forest ecosystems, influenced by meteorological factors and potentially constrained by soil moisture. We used Granier-type thermal dissipation probes to monitor xylem sap flow dynamics of three tree species (Quercus liaotungensis, Platycladus orientalis, and Robinia pseudoacacia) in a semi-arid loess hilly region, and to continuously monitor the key meteorological factors and soil water content (SWC). We established the SWC thresholds delineating soil moisture-limited and -unlimited sap flow responses to transpiration drivers. The results showed that mean sap flux density (Js) of Q. liaotungensis and R. pseudoacacia was significantly higher during period with higher soil moisture compared to lower soil moisture, while the difference in Js for P. orientalis between the two periods was not significant. We used an exponential saturation function to fit the relationship between the Js of each tree species and the integrated transpiration variable (VT) which reflected solar radiation and vapor pressure deficit. The difference in the fitting curve parameters indicated that there were distinct response patterns between Js and VT under different soil moisture conditions. There was a threshold in soil moisture limitation on sap flow for each species, which was identified as 0.129 m3·m-3 for Q. liaotungensis, 0.116 m3·m-3 for P. orientalis, and 0.108 m3·m-3 for R. pseudoacacia. Below the thresholds, Js was limited by soil moisture. Above these points, the normalized sensitivity index (NSI) for Q. liaotungensis and P. orientalis reached saturation, while that of R. pseudoacacia did not reach saturation but exhibited a significant reduction in moisture limitation. Among the three species, P. orientalis was the most capable of overcoming soil moisture constraints.
Assuntos
Transpiração Vegetal , Solo , Árvores , Água , Solo/química , Água/metabolismo , Água/análise , Árvores/crescimento & desenvolvimento , Árvores/fisiologia , Árvores/metabolismo , China , Quercus/fisiologia , Quercus/crescimento & desenvolvimento , Quercus/metabolismo , Ecossistema , Robinia/fisiologia , Robinia/crescimento & desenvolvimento , Robinia/metabolismo , Florestas , Xilema/fisiologia , Xilema/metabolismo , Exsudatos de Plantas/metabolismoRESUMO
PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.
Assuntos
Senilidade Prematura , Medicamentos de Ervas Chinesas , Qualidade de Vida , Humanos , Método Duplo-Cego , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Pessoa de Meia-Idade , Feminino , Idoso , Senilidade Prematura/tratamento farmacológico , Adulto , Telomerase , Força da Mão , Estudos Prospectivos , Telômero/efeitos dos fármacosRESUMO
OBJECTIVE: To explore the effect and mechanism of Dahuang Zhechong Pill (DHZCP) on liver fibrosis. METHODS: Liver fibrosis cell model was induced by transforming growth factor-ß (TGF-ß) in hepatic stellate cells (HSC-T6). DHZCP medicated serum (DMS) was prepared in rats. HSC-T6 cells were divided into the control (15% normal blank serum culture), TGF-ß (15% normal blank serum + 5 ng/mL TGF-ß), DHZCP (15% DMS + 5 ng/mL TGF-ß), DHZCP+PDTC [15% DMS + 4 mmol/L ammonium pyrrolidine dithiocarbamate (PDTC)+ 5 ng/mL TGF-ß], and PDTC groups (4 mmol/L PDTC + 5 ng/mL TGF-ß). Cell activity was detected by cell counting kit 8 and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the cell supernatant were determined by enzyme-linked immunosorbnent assay. Western blot was used to measure the expressions of p38 mitogen-activated protein kinase/nuclear factor kappa B/transforming growth factor-ß1 (p38 MAPK/NF-κ B/TGF-ß1) pathway related proteins, and the localization and expressions of these proteins were observed by immunofluorescence staining. RESULTS: DHZCP improves the viability of cells damaged by TGF-ß and reduces inflammatory cytokines and ALT and AST levels in the supernatant of HSC-T6 cells induced with TGF-ß (P<0.05 or P<0.01). Compared with the TGF-ß group, NF-κ B p65 levels in the DHZCP group were decreased (P<0.05). p38 MAPK and NF-κ B p65 levels in the DHZCP+PDTC were also reduced (P<0.01). Compared with the TGF-ß group, the protein expression of Smad2 showed a downward trend in the DHZCP, DHZCP+PDTC, and PDTC groups (all P<0.01), and the decreasing trend of Samd3 was statistically significant only in DHZCP+PDTC group (P<0.01), whereas Smad7 was increased (P<0.05 or P<0.01). CONCLUSION: DHZCP can inhibit the process of HSC-T6 cell fibrosis by down-regulating the expression of p38 MAPK/NF-κ B/TGF-ß1 pathway.
RESUMO
Recent breakthroughs in cancer immunology have propelled immunotherapy to the forefront of cancer research as a promising treatment approach that harnesses the body's immune system to effectively identify and eliminate cancer cells. In this study, three novel cyclometalated Ir(III) complexes, Ir1, Ir2, and Ir3, were designed, synthesized, and assessed in vitro for cytotoxic activity against several tumor-derived cell lines. Among these, Ir1 exhibited the highest cytotoxic activity, with an IC50 value of 0.4 ± 0.1 µM showcasing its significant anticancer potential. Detailed mechanistic analysis revealed that co-incubation of Ir1 with 143B cells led to Ir1 accumulation within mitochondria and the endoplasmic reticulum (ER). Furthermore, Ir1 induced G0/G1 phase cell cycle arrest, while also diminishing mitochondrial membrane potential, disrupting mitochondrial function, and triggering ER stress. Intriguingly, in mice the Ir1-induced ER stress response disrupted calcium homeostasis to thereby trigger immunogenic cell death (ICD), which subsequently activated the host antitumor immune response while concurrently dampening the in vivo tumor-induced inflammatory response.
Assuntos
Antineoplásicos , Complexos de Coordenação , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Morte Celular Imunogênica , Irídio , Mitocôndrias , Irídio/química , Irídio/farmacologia , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Morte Celular Imunogênica/efeitos dos fármacos , Animais , Camundongos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Linhagem Celular Tumoral , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
Listeria monocytogenes biofilms formed on food-contact surfaces within food-processing facilities pose a significant challenge, serving as persistent sources of cross-contamination. In this review, we examined documented cases of foodborne outbreaks and recalls linked to L. monocytogenes contamination on equipment surfaces and in the food production environment, provided an overview of the prevalence and persistence of L. monocytogenes in different food-processing facilities, and discussed environmental factors influencing its biofilm formation. We further delved into antimicrobial interventions, such as chemical sanitizers, thermal treatments, biological control, physical treatment, and other approaches for controlling L. monocytogenes biofilms on food-contact surfaces. This review provides valuable insights into the persistent challenge of L. monocytogenes biofilms in food processing, offering a foundation for future research and practical strategies to enhance food safety.
Assuntos
Biofilmes , Microbiologia de Alimentos , Listeria monocytogenes , Listeria monocytogenes/fisiologia , Biofilmes/crescimento & desenvolvimento , Manipulação de Alimentos/métodos , Contaminação de Alimentos/prevenção & controle , Contaminação de Equipamentos/prevenção & controleRESUMO
CLINICAL RELEVANCE: The pathogenesis of chronic dacryocystitis (CDC) is associated with a variety of bacteria. Investigating microflora has the potential to provide a theoretical basis for preventing and treating CDC. BACKGROUND: 16S rRNA sequencing is a sequence-based bacterial analysis. The application of 16S rRNA sequencing in CDC is rarely reported. METHODS: A case-control study of infected and healthy eyes diagnosed as CDC patients was conducted. Seventy-eight patients were divided into A (conjunctival sac secretions from healthy eyes), B (conjunctival sac secretions from affected eyes), and C (lacrimal sac secretions from affected eyes) groups. The flora of samples was analysed with 16S rRNA sequencing, and the data was analysed using QIIME, R, LefSE and other software. The potential functions were analysed by PICRUSt. RESULTS: A total of 1440 operational taxonomic units (OTUs) were obtained, 139 specific to group A, 220 specific to group B, and 239 specific to group C. There was no significant difference in α index between the three groups. The beta diversity and grouping analysis data indicated that the three groups of flora were similar in species richness and diversity, but there were some differences in composition. In group A, the abundance of Pseudomonadaceae, Chlorobacteria, Moraceae, Staphylococcaceae, Bacillariophyceae, Immunobacterium spp. and Bacillus spp. was higher; in group B, the abundance of Burkholderiaceae, Sphingomonas, Rhizobia, Stalked Bacteria, Sphingomonadaceae, Enterobacteriaceae, Shortwaveomonas spp. was higher; in group C, the abundance of Streptococcus digestiveis, Propionibacterium, Enterobacteriaceae, Anaerobacteriaceae, Propionibacteriaceae, Bacillus spp. Neisseria spp. and Shortactomonas spp. was higher. Six pathways were identified to assess the potential microbial functions. CONCLUSION: Alterations in the microbiota of the conjunctiva and lacrimal sac are associated with the pathogenesis of CDC, which may provide certain guidance for antibiotic treatment of CDC.
RESUMO
In this study, a series of collagen-chitosan-eugenol (CO-CS-Eu) flow-casting composite films were prepared using collagen from sturgeon skin, chitosan, and eugenol. The physicochemical properties, mechanical properties, microstructure, as well as antioxidant and antimicrobial activities of the composite membranes were investigated by various characterization techniques. The findings revealed that the inclusion of eugenol augmented the thickness of the film, darkened its color, reduced the transparency, and enhanced the ultraviolet light-blocking capabilities, with the physicochemical properties of the CO-CS-0.25%Eu film being notably favorable. Eugenol generates increasingly intricate matrices that disperse within the system, thereby modifying the optical properties of the material. Furthermore, the tensile strength of the film decreased from 70.97 to 20.32 MPa, indicating that eugenol enhances the fluidity and ductility of the film. Added eugenol also exhibited structural impact by loosening the film cross-section and decreasing its density. The Fourier transform infrared spectroscopy results revealed the occurrence of several intermolecular interactions among collagen, chitosan, and eugenol. Moreover, the incorporation of eugenol bolstered the antioxidant and antimicrobial capabilities of the composite film. This is primarily attributed to the abundant phenolic/hydroxyl groups present in eugenol, which can react with free radicals by forming phenoxy groups and neutralizing hydroxyl groups. Consequently, inclusion of eugenol substantially enhances the freshness retention performance of the composite film. PRACTICAL APPLICATION: â The CO-CS-Eu film utilizes collagen from sturgeon skin, improving the use of sturgeon resources.â Different concentrations of eugenol altered its synergistic effect with chitosan.â The CO-CS-Eu film is composed of natural products with safe and edible properties.