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Immunity, Inflammation and Disease Jun 2024The ongoing outbreak of the respiratory disease coronavirus disease 2019 (COVID-19) is currently presenting a major global health threat. This pandemic is unprecedented...
OBJECTIVE
The ongoing outbreak of the respiratory disease coronavirus disease 2019 (COVID-19) is currently presenting a major global health threat. This pandemic is unprecedented in recent human history. The objective of this study was to examine the relationship between cycle quantitation (Cq) and laboratory parameters in COVID-19 patients, aiming to determine if Cq levels can provide valuable insights into the COVID-19 disease.
METHODS
This study involved 234 participants who were divided into case and control groups. Real-time PCR tests were used to diagnose COVID-19 cases in the study participants. Blood tests, including complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), D-dimer, IgG, and IgM, were also conducted. Statistical analysis was performed using SPSS 22 software.
RESULTS
The findings showed that COVID-19-positive cases had significantly higher levels of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), D-dimer, ESR, CRP, and LDH compared to normal cases. Additionally, the case group had significantly lower lymphocyte and platelet counts. There was a statistically significant positive correlation between Cq levels and lymphocyte count (r = .124, p = .014). Conversely, there was a statistically significant inverse correlation between Cq levels and NLR (r = -.208, p = .017). Furthermore, the evaluation of hematological, inflammatory, and biochemical indexes in COVID-19 patients using the receiver-operating characteristics curve demonstrated statistically appropriate sensitivity and specificity.
CONCLUSION
Our outcomes indicated a significant association between Cq levels and PLR, NLR, D-dimer, CRP, and ESR in COVID-19 patients. Consequently, including the report of laboratory parameters alongside Cq values offers a promising prognosis.
Topics: Humans; COVID-19; Male; Female; Middle Aged; SARS-CoV-2; Adult; C-Reactive Protein; Fibrin Fibrinogen Degradation Products; Blood Sedimentation; Aged; Neutrophils; Platelet Count; L-Lactate Dehydrogenase; Case-Control Studies; Lymphocytes
PubMed: 38923849
DOI: 10.1002/iid3.1326 -
ELife Jun 2024During tuberculosis (TB), migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid...
During tuberculosis (TB), migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid development of protective T-cell-mediated immunity. However, the mechanisms involved in the delayed migration of DCs during TB are still poorly defined. Here, we found that infection of DCs with (Mtb) triggers HIF1A-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the lactate dehydrogenase inhibitor oxamate and the HIF1A inhibitor PX-478 abrogated Mtb-induced DC migration in vitro to the lymphoid tissue-specific chemokine CCL21, and in vivo to lymph nodes in mice. Strikingly, we found that although monocytes from TB patients are inherently biased toward glycolysis metabolism, they differentiate into poorly glycolytic and poorly migratory DCs compared with healthy subjects. Taken together, these data suggest that because of their preexisting glycolytic state, circulating monocytes from TB patients are refractory to differentiation into migratory DCs, which may explain the delayed migration of these cells during the disease and opens avenues for host-directed therapies for TB.
Topics: Dendritic Cells; Glycolysis; Monocytes; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mycobacterium tuberculosis; Cell Movement; Animals; Tuberculosis; Mice; Toll-Like Receptor 2; Mice, Inbred C57BL; Female
PubMed: 38922679
DOI: 10.7554/eLife.89319 -
Sports (Basel, Switzerland) Jun 2024The primary aim of the present investigation was to compare the acute physiological and perceptual responses between two modes of interval training using a randomized...
The primary aim of the present investigation was to compare the acute physiological and perceptual responses between two modes of interval training using a randomized crossover design. More specifically, eleven young adult participants (23 ± 4 years, 77 ± 13 kg, 178 ± 7 cm) performed two protocols: one composed of whole-body calisthenics exercises and another on a cycle ergometer. Both protocols encompassed eight 20 s bouts at intensities equivalent to all-out (HIIT-WB) and 170% of the maximal power output (HIIT-C), respectively, interspersed with 10 s of passive rest. The peak and average heart rate, the rating of perceived effort, and blood lactate, creatine kinase, and lactate dehydrogenase concentrations were measured. Aside from blood lactate (HIIT-WB = 9.4 ± 1.8 mmo/L; HIIT-C = 12.5 ± 2.5 mmol/L, < 0.05) and the rating of perceived exertion (HIIT-WB = 8.8 ± 0.9; HIIT-C = 9.6 ± 0.5, < 0.05), physiological responses did not significantly differ between protocols (all > 0.05), with high average heart rate values (HIIT-WB = 86 ± 6% HRmax; HIIT-C = 87 ± 4% HRmax) and a low magnitude of muscle damage, as inferred by CK and LDH concentrations (HIIT-WB = 205.9 ± 56.3 and 203.5 ± 72.4 U/L; HIIT-C = 234.5 ± 77.1 and 155.1 ± 65.3 U/L), respectively. It can be concluded that both protocols elicit vigorous heart rate responses and a low magnitude of muscle damage and, therefore, appear as viable alternatives to improve aerobic fitness. The inclusion of a whole-body HIIT protocol may be an interesting alternative for training prescription in relation to more common interval training protocols.
PubMed: 38921860
DOI: 10.3390/sports12060166 -
Journal of Functional Biomaterials May 2024Computer-aided design and computer-aided manufacturing (CAD/CAM) techniques are based on either subtractive (milling prefabricated blocks) or additive (3D printing)...
Computer-aided design and computer-aided manufacturing (CAD/CAM) techniques are based on either subtractive (milling prefabricated blocks) or additive (3D printing) methods, and both are used for obtaining dentistry materials. Our in vitro study aimed to investigate the behavior of human gingival fibroblasts exposed to methacrylate (MA)-based CAD/CAM milled samples in comparison with that of MA-based 3D-printed samples to better elucidate the mechanisms of cell adaptability and survival. The proliferation of human gingival fibroblasts was measured after 2 and 24 h of incubation in the presence of these samples using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the membrane integrity was assessed through the lactate dehydrogenase release. The level of reactive oxygen species, expression of autophagy-related protein LC3B-I, and detection of GSH and caspase 3/7 were evaluated by fluorescence staining. The MMP-2 levels were measured using a Milliplex MAP kit. The incubation with MA-based 3D-printed samples significantly reduced the viability, by 16% and 28% from control after 2 and 24 h, respectively. There was a 25% and 55% decrease in the GSH level from control after 24 h of incubation with the CAD/CAM milled and 3D-printed samples, respectively. In addition, higher levels of LC3B-I and MMP-2 were obtained after 24 h of incubation with the MA-based 3D samples compared to the CAD/CAM milled ones. Therefore, our results outline that the MA-CAD/CAM milled samples displayed good biocompatibility during 24-h exposure, while MA-3D resins are proper for short-term utilization (less than 24 h).
PubMed: 38921521
DOI: 10.3390/jfb15060147 -
Journal of Fungi (Basel, Switzerland) May 2024Biocolourants could be a sustainable option for dyes that require fossil-based chemicals in their synthesis. We studied the in vitro toxicity of anthraquinone aglycone...
Biocolourants could be a sustainable option for dyes that require fossil-based chemicals in their synthesis. We studied the in vitro toxicity of anthraquinone aglycone extract obtained from fungus and compared it to the toxicity of its two main components, emodin and previously studied dermocybin. Cell viability, cytotoxicity, and oxidative stress responses in HepG2 liver and THP-1 immune cell lines were studied along with skin sensitisation. In addition, genotoxicity was studied with comet assay in HepG2 cells. Cellular viability was determined by MTT, propidium iodide, and lactate dehydrogenase assays, which showed that the highest doses of both the aglycone extract and emodin affected the viability. However, the effect did not occur in all of the used assays. Notably, after both exposures, a dose-dependent increase in oxidative stress factors was observed in both cell lines as measured by MitoSOX and dihydroethidium assays. extract was not genotoxic in the comet assay. Importantly, both emodin and the extract activated the skin sensitisation pathway in the KeratinoSens assay, suggesting that they can induce allergy in humans. As emodin has shown cytotoxic and skin-sensitising effects, it is possible that the adverse effects caused by the extract are also mediated by it since it is the main component present in the fungus.
PubMed: 38921356
DOI: 10.3390/jof10060369 -
Cells Jun 2024Cancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to...
Cancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase (LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast (BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were mainly increased in the micromolar concentrations of the studied compounds in both cell lines. Les-3467 and Les-4369 increased the mRNA expression of , (tumor protein P53), and (ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except ) was mainly decreased in the A549 cells treated with both of the tested compounds. Our results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown the PPARγ modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer properties evidenced by their action at high concentrations and non-selective effects against BJ and A549 cells.
Topics: Humans; A549 Cells; PPAR gamma; Reactive Oxygen Species; Pyrazoles; Thiazolidines; Indoles; Caspase 3; Tumor Suppressor Protein p53; Cell Proliferation; Antineoplastic Agents; Ataxia Telangiectasia Mutated Proteins; Apoptosis; Fibroblasts
PubMed: 38920636
DOI: 10.3390/cells13121007 -
Infection and Drug Resistance 2024Myocardial injury is common in severe fever with thrombocytopenia syndrome (SFTS) patients. Currently, research on the prognostic value of cardiac troponin I (cTnI) for...
BACKGROUND
Myocardial injury is common in severe fever with thrombocytopenia syndrome (SFTS) patients. Currently, research on the prognostic value of cardiac troponin I (cTnI) for predicting the mortality of SFTS patients, especially death within 7 days is limited.
METHODS
Between May 2011 and October 2022, clinical and laboratory data on admission of consecutive SFTS cases were collected from six medical centres in China. The clinical endpoint was in-hospital all-cause death within seven days. Risk factors of myocardial injury and death were analysed using multivariable regression models. Prognostic models were established using Cox regression and performance of indicators was evaluated in terms of calibration, discrimination.
RESULTS
A total of 1379 laboratory-confirmed patients were enrolled, in which 686 subjects were included for analysis. The median age was 66 years, with 48.1% of male. Eighty-seven patients died within seven days and 396 patients diagnosed with myocardial injury during hospitalization. Non-survivors had significant higher levels of cardiac indices than survivors, including cTnI, aspartic transaminase (AST) and lactate dehydrogenase (LDH). Elevated levels of cTnI (HR = 1.058, 95% CI:1.032-1.085), AST (HR = 1.191, 95% CI:1.150-1.234) and LDH (HR = 1.019, 95% CI:1.009-1.029) predicted risk of early in-hospital mortality. cTnI model performed best, with area under curve of 0.850 (0.774-0.926) and concordance index of 0.842, respectively. Statistical differences were found between high and low levels of cTnI for mortality (<0.001) using 0.35 ng/mL as the optimal cut-off.
CONCLUSION
The risk of early in-hospital death can be predicted by cTnI. Clinical doctors should remind vigilant concerning the elevation of cardiac enzyme as soon as possible.
PubMed: 38919833
DOI: 10.2147/IDR.S463251 -
International Journal of General... 2024To explore the predictive factors and predictive model construction for the progression of prostate cancer bone metastasis to castration resistance.
Development and Validation of a Clinic Machine Learning Classifier for the Prediction of Risk Stratifications of Prostate Cancer Bone Metastasis Progression to Castration Resistance.
OBJECTIVE
To explore the predictive factors and predictive model construction for the progression of prostate cancer bone metastasis to castration resistance.
METHODS
Clinical data of 286 patients diagnosed with prostate cancer with bone metastasis, initially treated with endocrine therapy, and progressing to metastatic castration resistant prostate cancer (mCRPC) were collected. By comparing the differences in various factors between different groups with fast and slow occurrence of castration-resistant prostate cancer (CRPC). Kaplan-Meier survival analysis and COX multivariate risk proportional regression model were used to compare the differences in the time to progression to CRPC in different groups. The COX multivariate risk proportional regression model was used to evaluate the impact of candidate factors on the time to progression to CRPC and establish a predictive model. The accuracy of the model was then tested using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).
RESULTS
The median time for 286 mCRPC patients to progress to CRPC was 17 (9.5-28.0) months. Multivariate analysis showed that the lowest value of PSA (PSA nadir), the time when PSA dropped to its lowest value (timePSA), and the number of BM, and LDH were independent risk factors for rapid progression to CRPC. Based on the four independent risk factors mentioned above, a prediction model was established, with the optimal prediction model being a random forest with area under curve (AUC) of 0.946[95% CI: 0.901-0.991] and 0.927[95% CI: 0.864-0.990] in the training and validation cohort, respectively.
CONCLUSION
After endocrine therapy, the PSA nadir, timePSA, the number of BM, and LDH are the main risk factors for rapid progression to mCRPC in patients with prostate cancer bone metastases. Establishing a CRPC prediction model is helpful for early clinical intervention decision-making.
PubMed: 38919704
DOI: 10.2147/IJGM.S465031 -
BMC Veterinary Research Jun 2024In vitro embryo production is a highly demanded reproductive technology in horses, which requires the recovery (in vivo or post-mortem) and in vitro maturation (IVM) of...
BACKGROUND
In vitro embryo production is a highly demanded reproductive technology in horses, which requires the recovery (in vivo or post-mortem) and in vitro maturation (IVM) of oocytes. Oocytes subjected to IVM exhibit poor developmental competence compared to their in vivo counterparts, being this related to a suboptimal composition of commercial maturation media. The objective of this work was to study the effect of different concentrations of secretome obtained from equine preovulatory follicular fluid (FF) on cumulus-oocyte complexes (COCs) during IVM. COCs retrieved in vivo by ovum pick up (OPU) or post-mortem from a slaughterhouse (SLA) were subjected to IVM in the presence or absence of secretome (Control: 0 µg/ml, S20: 20 µg/ml or S40: 40 µg/ml). After IVM, the metabolome of the medium used for oocyte maturation prior (Pre-IVM) and after IVM (Post-IVM), COCs mRNA expression, and oocyte meiotic competence were analysed.
RESULTS
IVM leads to lactic acid production and an acetic acid consumption in COCs obtained from OPU and SLA. However, glucose consumption after IVM was higher in COCs from OPU when S40 was added (Control Pre-IVM vs. S40 Post-IVM: 117.24 ± 7.72 vs. 82.69 ± 4.24; Mean µM ± SEM; p < 0.05), while this was not observed in COCs from SLA. Likewise, secretome enhanced uptake of threonine (Control Pre-IVM vs. S20 Post-IVM vs. S40 Post-IVM: 4.93 ± 0.33 vs. 3.04 ± 0.25 vs. 2.84 ± 0.27; Mean µM ± SEM; p < 0.05) in COCs recovered by OPU. Regarding the relative mRNA expression of candidate genes related to metabolism, Lactate dehydrogenase A (LDHA) expression was significantly downregulated when secretome was added during IVM at 20-40 µg/ml in OPU-derived COCs (Control vs. S20 vs. S40: 1.77 ± 0.14 vs. 1 ± 0.25 vs. 1.23 ± 0.14; fold change ± SEM; p < 0.05), but not in SLA COCs.
CONCLUSIONS
The addition of secretome during in vitro maturation (IVM) affects the gene expression of LDHA, glucose metabolism, and amino acid turnover in equine cumulus-oocyte complexes (COCs), with diverging outcomes observed between COCs retrieved using ovum pick up (OPU) and slaughterhouse-derived COCs (SLA).
Topics: Animals; Horses; Oocytes; Follicular Fluid; In Vitro Oocyte Maturation Techniques; Cumulus Cells; Female; Culture Media; Secretome
PubMed: 38918770
DOI: 10.1186/s12917-024-04129-1 -
Testicular Mixed Germ Cell Tumor (TMGCT) Management: Addressing Infection and Tumor Marker Dynamics.Cureus May 2024We report the case of a 23-year-old male presenting with right testicular swelling, post-coital pain, and fever. Initial MRI and local examination suggested testicular...
We report the case of a 23-year-old male presenting with right testicular swelling, post-coital pain, and fever. Initial MRI and local examination suggested testicular carcinoma. Elevated serum alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) levels were observed. Biopsy confirmed a mixed germ cell tumor (MGCT). Concurrently, the patient was diagnosed with an infection and treated with antibiotics. Remarkably, following antibiotic therapy, fever resolved, and tumor marker levels significantly decreased. Subsequent orchidectomy confirmed the diagnosis of MGCT. This case underscores the importance of recognizing and treating concurrent infections, which may influence both clinical presentation and tumor marker levels in testicular germ cell tumors.
PubMed: 38915994
DOI: 10.7759/cureus.61062