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Molecules (Basel, Switzerland) Jun 2024In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This...
In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.
Topics: Humans; Sesquiterpenes; Lactones; Antineoplastic Agents; Cell Line, Tumor; Piperidones; Glycolysis; Cell Proliferation; Molecular Docking Simulation; Neoplasms; Drug Screening Assays, Antitumor
PubMed: 38930831
DOI: 10.3390/molecules29122765 -
Microorganisms Jun 2024When animals perceive an acute stressor like a predator, they typically undergo a suite of physiological changes that function to improve survival during the encounter,...
When animals perceive an acute stressor like a predator, they typically undergo a suite of physiological changes that function to improve survival during the encounter, such as elevation in cardiac output, to supply more energy to muscles. If bodily energy is limited, such as by parasites or infections, these functions could become less efficient and lessen host survival. In the aquatic world of microorganisms, individuals can become colonized by other organisms on their surface (epibionts), which could sap energy from their host from their weight, or even compete with the host for food. Here, we tested if one epibiont (a ciliated protozoan, spp.) affects its hosts' ability to mount a physiological stress reaction. We collected wild daphnia () that had varying burdens of these on their bodies and exposed them to a simulated stressor (crushed daphnia, to simulate nearby predation) under a microscope while monitoring for changes in their heart rates in real time. Out of 121 daphnia, those with no epibionts showed no meaningful changes in their heart rate after exposure, but those with light or heavy burdens showed immediate elevations (within 5 min). Moreover, the heart rates of heavily burdened daphnia continued to rise for 1.5 h thereafter, to as much as 17% higher than at baseline. These patterns were unexpected, as they suggest that the ciliated epibionts act to elevate their hosts' physiological reaction, rather than dampen it, perhaps by churning the water column around the host, thereby enhancing the chemical alarm cue. The procedures used in this study may be useful for future investigations into the acute stress reactions of daphnia or other microorganisms.
PubMed: 38930601
DOI: 10.3390/microorganisms12061219 -
Microorganisms Jun 2024Currently available numerical models that describe the fecal contamination of aquatic environments using as an indicator bacterium did not consider its survival in...
Currently available numerical models that describe the fecal contamination of aquatic environments using as an indicator bacterium did not consider its survival in sediments. We conducted a series of comparative experiments to reveal the independent and interactive effects of sediment factors, including temperature, pH, water-extractable total dissolved solids (TDSs), coexisting microbes, and sampling sites, in lake environments on survival. In experiments, survival was observed by controlling any two factors at a time. Consequently, the decrease in pH and presence of coexisting microbes enhanced die-off, whereas the addition of water-extractable TDSs promoted its growth. To select factors to be considered for modelling survival in sediments, the independent effects of each factor and the interaction effect of the two factors were statistically compared based on their effect sizes (η). As a result, pH (η = 59.5-89.0%) affected survival most significantly, followed by coexisting microbes (1.7-48.4%). Among the interactions affecting survival, including pH or coexisting microbes-which had larger independent effects-relatively larger statistically significant interactions were observed between pH and coexisting microbes (31.1%), coexisting microbes and water-extractable TDSs (85.4%), and coexisting microbes and temperature (26.4%).
PubMed: 38930574
DOI: 10.3390/microorganisms12061192 -
Microorganisms Jun 2024serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic...
serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic infection in chickens remains unclear. Thioredoxin reductase (TrxB) is a redox protein crucial for regulating various enzyme activities in serovar, but the role in SG-induced chicken systemic infection has yet to be determined. Here, we constructed a mutant SG strain lacking the gene (::Cm) and used chicken embryo inoculation and chicken oral infection to investigate the role of gene in the pathogenicity of SG. Our results showed that ::Cm exhibited no apparent differences in colony morphology and growth conditions but exhibited reduced tolerance to HO and increased resistance to bile acids. In the chicken embryo inoculation model, there was no significant difference in the pathogenicity of ::Cm and wild-type (WT) strains. In the chicken oral infection, the WT-infected group exhibited typical clinical symptoms of fowl typhoid, with complete mortality between days 6 and 9 post infection. In contrast, the ::Cm group showed a 100% survival rate, with no apparent clinical symptoms or pathological changes observed. The viable bacterial counts in the liver and spleen of the ::Cm-infected group were significantly reduced, accompanied by decreased expression of cytokines and chemokines (IL-1β, IL-6, IL-12, CXCLi1, TNF-α, and IFN-γ), which were significantly lower than those in the WT group. These results show that the pathogenicity of the -deficient strain was significantly attenuated, indicating that the gene is a crucial virulence factor in SG-induced systemic infection in chickens, suggesting that may become a potentially effective target for controlling and preventing SG infection in chickens.
PubMed: 38930562
DOI: 10.3390/microorganisms12061180 -
Microorganisms Jun 2024Orchids are crucial for the horticulture industry. Mycorrhizal fungi benefit crops by improving nutrition, plant growth, and disease resistance. However, the mycorrhizal...
Orchids are crucial for the horticulture industry. Mycorrhizal fungi benefit crops by improving nutrition, plant growth, and disease resistance. However, the mycorrhizal association of horticultural hybrid orchids is poorly understood. To address this, we investigated mycorrhizal colonization in the entire root system and assessed the mycorrhizal community using a cultivar, . Stardust 'Firebird', obtained from three nurseries. Additionally, we isolated and tested mycorrhizal fungi in symbiotic culture to assess their role in the seed germination and growth of species. All plants were colonized by mycorrhizal fungi, with a higher colonization rate in mature than in juvenile plants. Molecular identification of mycorrhizal fungi by Sanger and high-throughput sequencing revealed that the cultivar was associated with a phylogenetically diverse group of fungi, including mycorrhizal fungi from Tulasnellaceae, and several wood-decaying fungi. The Tulasnellaceae isolates significantly enhanced the seed germination of three species and increased the survival rate and growth of asymbiotic seedlings of . This study is the first comprehensive examination of mycorrhizal associations in horticultural orchid hybrids, providing valuable insights for commercial production.
PubMed: 38930558
DOI: 10.3390/microorganisms12061176 -
Microorganisms Jun 2024The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, () has relatively less...
The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, () has relatively less research on its antibacterial infection in vivo, and its protective effect and mechanism still need to be fully studied. In this study, we selected 23017, which can regulate the intestinal immunity of the host animal and resist pathogen infection, to evaluate its protective role and potential molecular mechanisms in the mouse model of C7731 infection. As expected, we confirmed that 23017 reduced the diarrhea rate and increased the daily weight gain and survival rate of the mouse model, and inhibited colonization in the jejunum and liver. It also reduced the level of oxidative damage and protected the integrity of intestinal tissue by increasing the activity of intestinal antioxidant enzymes (SOD, GSH-Px and T-AOC). From the perspective of intestinal mucosal barrier injury and repair, it was confirmed that 23017 could increase the expression levels of intestinal tight junction proteins (ZO-1 and OCLN). Our research results also show that 23017 inhibits the inflammatory response and promotes the occurrence of cellular immunity in the body by promoting the increase in IL-10 and inhibiting IL-13 in serum and intestinal tissue. Notably, 23017 increased total secretory immunoglobulin A (SIgA) levels in the intestine, which were closely associated with elevated levels of IL-5, IL-13, pIgR, j-chain, and IgAα-chain. In addition, 23017 increased the expression of antioxidant proteins Nrf2, NQO1, and HO-1 associated with Nrf2 signaling to inhibit intestinal oxidative damage. This mechanism may be responsible for its protective effect against -infected intestine. Our study provides new evidence and theoretical support for the analysis of the anti-bacterial infection effect and mechanism of , which will contribute to the development of and the treatment of pathogenic bacteria intestinal infection.
PubMed: 38930517
DOI: 10.3390/microorganisms12061135 -
Microorganisms May 2024is an emerging human pathogen that has a high rate of incidence in immunocompromised individuals. We have found a putative secondary metabolite pathway within , which...
is an emerging human pathogen that has a high rate of incidence in immunocompromised individuals. We have found a putative secondary metabolite pathway within , which may be a key factor in its pathogenesis. This novel pathway is encoded in a gene cluster spanning MAB_0284c to 0305 and is related to pathways, producing the secondary metabolites streptonigrin and nybomycin. We constructed an in-frame deletion of the MAB_0295 () gene and tested it in our animal model. We have previously shown that tadpoles, which have functional lungs and T cells, can serve as a reliable comparative model for persistent infection and pathogenesis. Here, we report that tadpoles intraperitoneally infected with the ∆ mutant exhibit early decreased bacterial loads and significantly increased survival compared with those infected with WT . ∆ mutant also induced lower transcript levels of several pro-inflammatory cytokines (, , , ) than those of WT in the liver and lungs. In addition, there was impaired macrophage recruitment and decreased macrophage infection in tadpoles infected with the ∆ mutant, by tail wound inoculation, compared to those infected with the WT bacteria, as assayed by intravital confocal microscopy. These data underline the relevance and usefulness of tadpoles as a novel comparative animal model to identify genetic determinants of immunopathogenesis, suggesting a role for this novel and uncharacterized pathway in pathogenesis and macrophage recruitment.
PubMed: 38930501
DOI: 10.3390/microorganisms12061120 -
Journal of Clinical Medicine Jun 2024Shorter hip stems have shown promising mid-term results but lack long-term data. High rates of distal cortical hypertrophy (CH) have been described, suggesting a more...
The Migration Pattern of a Short-Tapered Femoral Stem Correlates with the Occurrence of Cortical Hypertrophies: A 10-Year Longitudinal Study Using Ein Bild Röntgen Analyse-Femoral Component Analysis.
Shorter hip stems have shown promising mid-term results but lack long-term data. High rates of distal cortical hypertrophy (CH) have been described, suggesting a more diaphyseal load transmission. This study aimed to determine patient-specific and surgery-related factors influencing CH and their impact on 10-year outcomes. : It included 100 consecutive total hip arthroplasties (THAs) using the Fitmore stem (Zimmer, Warsaw, Indiana), with clinical and radiographic follow-ups at 1, 2, 5, and at least 10 years post-surgery. : No revisions were performed due to aseptic loosening after a mean of 11.6 years (range: 10-13.5 years). CH was observed in 26% of hips, primarily in Gruen zones 3 and 5. There was no significant difference in the Harris Hip Score between patients with and without CH. Larger stem sizes and greater axial subsidence significantly correlated with CH occurrence (OD 1.80, (1.13-1.92), = 0.004; OD 1.47, (1.04-2.08), = 0.028). The Fitmore stem demonstrated excellent survival rates and favorable outcomes over 10 years. : Despite a lower CH rate compared to other studies, significant correlations with stem size and subsidence were identified. This study underscores the importance of patient selection and achieving high primary stability to maintain the metaphyseal anchoring concept.
PubMed: 38930145
DOI: 10.3390/jcm13123616 -
Journal of Clinical Medicine Jun 2024: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic...
: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. : We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised eight pediatric patients (ages 3-18) and two adult patients (ages 19-75). The median age at the time of SRS was 13 years, the median tumor volume accounted for 1.9 cc, the median biologically equivalent dose (BED) was 126 Gy, and the single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. : Following a median follow-up of 39 months (range: 6-78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. : Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (AREs) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial.
PubMed: 38930121
DOI: 10.3390/jcm13123592 -
Journal of Clinical Medicine Jun 2024Diabetes has a protective effect on abdominal aortic aneurysms (AAAs); however, there are contrasting reports on the impact of diabetes on endovascular aortic repair...
Diabetes has a protective effect on abdominal aortic aneurysms (AAAs); however, there are contrasting reports on the impact of diabetes on endovascular aortic repair (EVAR) outcomes, endoleaks (ELs) being the major negative outcome. The present study characterizes ELs and their outcomes in AAA patients, diabetic or not. This single-center, retrospective, comparative study was carried out on 324 AAA patients who underwent elective EVARs between 2007 and 2016 at the University Hospital of Liège (Belgium). The primary endpoint was the incidence and effect of ELs on the evolution of the aneurysmal sac; the secondary endpoints were surgical reintervention and mortality rate. Diabetic and non-diabetic patients were compared with respect to various risk factors by logistic regression, while a Cox regression was used to analyze survival. In AAA patients meeting the inclusion criteria (n = 248), 23% were diabetic. EL incidence was comparable ( = 0.74) in diabetic (38.7%) vs. non-diabetic (43.9%) patients. EL risk factors were age (HR = 1.04, = 0.014) and fibrate intake (HR = 3.12, = 0.043). A significant association was observed between ELs and aneurysm sac enlargement ( < 0.001), regardless of group ( = 0.46). Aneurysm sac regression per month for non-diabetic patients was -0.24 ± 0.013, while for diabetics it was -0.18 ± 0.027 ( = 0.059). Dyslipidemia (HR = 3.01, = 0.0060) and sulfonylureas (HR = 8.43, = 0.043) were associated with shorter EL duration, while diabetes (HR = 0.080, = 0.038) and beta blockers (HR = 0.46, = 0.036) were associated with longer EL duration. The likelihood of reoperation decreased with more recent surgery (OR = 0.90, = 0.040), regardless of diabetic status. All-cause mortality was higher for the non-diabetic group (45.5% vs. 26.3%, = 0.0096). Endoleak occurrence is a known risk factor for sac expansion. In diabetic patients, endoleaks lasted longer, and regression of the aneurysm sac tended to be slower. The number and type of reintervention was not related to the diabetic status of AAA patients, but overall survival was higher in patients with diabetes.
PubMed: 38930080
DOI: 10.3390/jcm13123551