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Neoplasia (New York, N.Y.) Jun 2024Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family,...
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family, has shown promising therapeutic potential and a good safety profile in both malignant pediatric central nervous system tumors (diffuse midline glioma [DMG]) and hematologic malignancies. ONC206 is a more potent analog of ONC201. However, the ONC206 potential and mechanism of action in HCC remain to be elucidated. We found that ONC206 hindered HCC growth by suppressing cell proliferation and inducing apoptosis. Moreover, ONC206 induced cytoprotective autophagy, and blocking autophagy enhanced the proapoptotic effect of ONC206. Additionally, ONC206 induced mitochondrial swelling, reduced the mitochondrial membrane potential (MMP), and led to the accumulation of mitochondrial ROS in HCC cells, ultimately resulting in mitochondrial dysfunction. The HCC patient samples exhibited notably elevated levels of caseinolytic protease proteolytic subunit (ClpP), which serves as a mediator of ONC206-induced mitochondrial dysfunction and the activation of protective autophagy. knockdown of ClpP reversed the cytotoxic effects of ONC206 on HCC cells. In summary, our results provide the first insight into the mechanism by which ONC206 exerts its anti-HCC effects and induces protective autophagy in HCC cells through ClpP.
PubMed: 38944913
DOI: 10.1016/j.neo.2024.101015 -
Advances in Gerontology = Uspekhi... 2024Research on the condition of the lungs in senile people is an urgent task. This is due to the fact that degenerative or age-associated changes in the respiratory system...
Research on the condition of the lungs in senile people is an urgent task. This is due to the fact that degenerative or age-associated changes in the respiratory system play an important role in the formation of senile asthenia syndrome and a decrease in the age-related viability of the body as a whole. CT-scans of patients aged 80-90 years were analyzed (n=31). Age-associated changes were evaluated: the presence of linear fibrosis, increased pulmonary pattern by the type of reticular (reticular) changes, the presence of gross fibrous reticular changes with cystic cavities and air bullae (by the type of «cellular lung»), as well as the presence of pulmonary emphysema. Most naturally, senile people show changes characteristic of linear pulmonary fibrosis and emphysema. The progression of the process leads to diffuse reticular changes in the interalveolar and intersegmental septa and, in adverse cases, to the formation of gross changes in the type of «cellular lung». Fibro-emphysematous changes are significantly more common in men. A microbiological study of the microbiota of the lower respiratory tract in elderly people was also carried out (n=16). When studying the microbiocenosis of the lower respiratory tract in elderly people, the following data were obtained: resident microflora was found in 71% and clinically significant microorganisms were found in 29%.
Topics: Humans; Aged, 80 and over; Male; Female; Pulmonary Emphysema; Microbiota; Lung; Tomography, X-Ray Computed; Pulmonary Fibrosis; Aging
PubMed: 38944785
DOI: No ID Found -
Journal of Agricultural and Food... Jun 2024The post-harvest fumigant, sulfuryl fluoride (SOF), is a >1000-fold more potent greenhouse gas than carbon dioxide and methane. Pilot studies have shown that SOF fumes...
The post-harvest fumigant, sulfuryl fluoride (SOF), is a >1000-fold more potent greenhouse gas than carbon dioxide and methane. Pilot studies have shown that SOF fumes vented from fumigation chambers can be captured and hydrolyzed by hydroxide (OH) and hydrogen peroxide (HO) at pH ∼ 12 in a scrubber, producing SO and F as waste salts. To reduce the costs and challenges associated with purchasing and mixing these reagents onsite, this study evaluates the electrochemical generation of OH and HO within spent scrubbing solution, taking advantage of the waste SO and F as free sources of electrolyte. The study used a gas diffusion electrode constructed from carbon paper coated with carbon black as a catalyst selective for the reduction of O to HO. Under galvanostatic conditions, the study evaluated the effect of electrochemical conditions, including applied cathodic current density and electrolyte strength. Within an electrolyte containing 200 mM SO and 400 mM F, comparable to the waste salts generated by a SOF scrubbing event, the system produced 250 mM HO at pH 12.6 within 4 h with a Faradaic efficiency of 98.8% for O reduction to HO. In a scrubbing-water sample from lab-scale fumigation, the system generated ∼200 mM HO at pH 13.5 within 4 h with a Faradaic efficiency of 75.6%. A comparison of the costs to purchase NaOH and HO against the electricity costs for electrochemical treatment indicated that the electrochemical approach could be 38-71% lower, depending on the local cost of electricity.
PubMed: 38944760
DOI: 10.1021/acs.jafc.4c00864 -
Mymensingh Medical Journal : MMJ Jul 2024This was a multicenter cohort study to evaluate the relationship between radiological findings and disability in moderate and severe head injury patients. The study...
This was a multicenter cohort study to evaluate the relationship between radiological findings and disability in moderate and severe head injury patients. The study places were the Neurosurgery department of Sylhet M A G Osmani Medical College Hospital, Sylhet Women's Medical College Hospital (SWMCH) and King Faisal Hospital (KFH), Taif, KSA. Sample size was 104 and the study period was 36 months (July 2021 to December 2022). On the basis of radiological findings the participants were divided into three arms. The different arms were diffused traumatic brain injury (arm-1), focal traumatic brain injury (arm-2) and both (diffused and traumatic) types traumatic brain injury (arm-3). Outcome was assessed by modified Rankin Score (mRS). Mean age was significantly higher in female. Overall mean age was 40.28 year. Highest number was in the below 20-year age group followed by the 41-50-year age group. Lowest number of participants was in the above 60-year group. Improved group was significantly higher than 'not improved' and the 'died' group (p<0.00001). Improved participants were significantly higher in the arm-1 and arm-2. Mortality was significantly higher (p<0.00001) in the arm-3 group.
Topics: Humans; Female; Adult; Middle Aged; Male; Cohort Studies; Craniocerebral Trauma; Young Adult; Brain Injuries, Traumatic; Adolescent; Aged; Disability Evaluation
PubMed: 38944732
DOI: No ID Found -
Mymensingh Medical Journal : MMJ Jul 2024In Intensive Care Units (ICUs) infection represents the most frequent complication leading to high mortality. Particularly the incidence of fungal infections, especially... (Observational Study)
Observational Study
In Intensive Care Units (ICUs) infection represents the most frequent complication leading to high mortality. Particularly the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years. Over last two decades there is predominance of Non albicans Candida (NAC) infection with increased isolation of novel species and decreased susceptibility. Early identification of Candida species and determination of antifungal susceptibility pattern is essential for effective management. Therefore, the study was conducted to isolate and identify Candida species from the blood samples of the patients suspected of candidemia and assess their antifungal susceptibility pattern. This cross-sectional, descriptive type of observational study was conducted in the Department of Microbiology, Mymensingh Medical College, Bangladesh from March 2021 to February 2022. Venous blood was collected from clinically suspected patients admitted at ICU, Neonatal Intensive Care Unit (NICU), Mymensingh Medical College Hospital, Bangladesh. Primary blood culture was performed by automated method followed by sub-culture in Saboraud's Dextrose Agar (SDA) and blood agar media. Candida species were recognized by phenotypic and genotypic methods. Antifungal susceptibility testing was done by disk diffusion and broth microdilution method (BMD). Out of 125 blood specimens collected, Candida species were isolated from 39(31.0%) blood samples of which NAC species were 35(89.0%) whereas C. albicans was only 4(10.2%). Eight (8) different Candida species were identified of which C. parapsilosis was predominant 16(41.0%). Rare and emerging drug resistant species of C. ciferrii 23.0%, C. auris 7.7%, C. rugosa 10.3%, C. lusitaniae 2.6% were also isolated. Candidemia was highest in neonate 33(84.61%) with male predominance 24(61.54%). Use of broad-spectrum antibiotics, prolonged hospital stay, pre-maturity and low birth weight (LBW) were found to be important risk factors. In candidemia the highest resistance was to Fluconazole-33% and lowest to Voriconazole-5%. The study showed that NAC species were more common with emergence of rare and multidrug resistant species.
Topics: Humans; Bangladesh; Candidemia; Cross-Sectional Studies; Female; Male; Candida; Antifungal Agents; Intensive Care Units; Microbial Sensitivity Tests; Infant, Newborn; Adult; Drug Resistance, Fungal
PubMed: 38944705
DOI: No ID Found -
Mymensingh Medical Journal : MMJ Jul 2024Antibiotics' usefulness is threatened by multi-drugs resistance in harmful microorganisms because of abuse and regulatory problems. Emerging microbes, resistance...
Antibiotics' usefulness is threatened by multi-drugs resistance in harmful microorganisms because of abuse and regulatory problems. Emerging microbes, resistance mechanisms and antimicrobial drugs all require extensive investigation. Evaluation of the in vitro antibacterial activity of Methanolic extracts isolated from Black pepper seeds (Piper nigrum L.) against two infection causing pathogens, Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. From July 2022 and June 2023, this experimental study was conducted at the Mymensingh Medical College's Department of Pharmacology and Therapeutics in conjunction with the Department of Microbiology. The solvents Methanol and 10.0% Di-Methyl Sulfoxide (DMSO) were used to make the extract. Using the disc diffusion and broth dilution methods, the antibacterial activity of methanolic extract of black pepper seeds (MBPE) was evaluated at various doses. Using the broth dilution procedure, the conventional antibiotic Ciprofloxacin was utilized, and the outcome was contrasted with that of Methanol extracts. Methanolic extract of black pepper seeds (MBPE) at seven distinct concentrations (100, 80, 60, 40, 20, 10 and 5mg/ml) were utilized, then later in chosen concentrations as needed to confirm the extracts' more precise margin of antimicrobial sensitivity. At 80mg/ml and above doses of the MBPE, it had an inhibitory impact against the aforementioned microorganisms. For Staphylococcus aureus and Pseudomonas aeruginosa the MIC were 60 and 70mg/ml in MBPE respectively. As of the MIC of Ciprofloxacin was 1μg/ml against Staphylococcus aureus and 1.5μg/ml for Pseudomonas aeruginosa. In comparison to MICs of MBPE for the test organisms, the MIC of Ciprofloxacin was the lowest. This study clearly shows that Staphylococcus aureus and Pseudomonas aeruginosa are sensitive to the methanolic extract of black pepper seeds' antibacterial properties.
Topics: Piper nigrum; Pseudomonas aeruginosa; Plant Extracts; Staphylococcus aureus; Seeds; Anti-Bacterial Agents; Microbial Sensitivity Tests; Methanol
PubMed: 38944702
DOI: No ID Found -
Academic Radiology Jun 2024Isocitrate dehydrogenase (IDH) and cyclin-dependent kinase inhibitor (CDKN) 2A/B status holds important prognostic value in diffuse gliomas. We aimed to construct...
PURPOSE
Isocitrate dehydrogenase (IDH) and cyclin-dependent kinase inhibitor (CDKN) 2A/B status holds important prognostic value in diffuse gliomas. We aimed to construct prediction models using clinically available and reproducible characteristics for predicting IDH-mutant and CDKN2A/B homozygous deletion in adult-type diffuse glioma patients.
MATERIALS AND METHODS
This retrospective, two-center study analysed 272 patients with adult-type diffuse glioma (230 for primary cohort and 42 for external validation cohort). Two radiologists independently assessed the patients' images according to the Visually AcceSAble Rembrandt Images (VASARI) feature set. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimise variable selection. Multivariable logistic regression analysis was used to develop the prediction models. Calibration plots, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) were used to validate the models. Nomograms were developed visually based on the prediction models.
RESULTS
The interobserver agreement between the two radiologists for VASARI features was excellent (κ range, 0.813-1). For the IDH-mutant prediction model, the area under the curves (AUCs) was 0.88-0.96 in the internal and external validation sets, For the CDKN2A/B homozygous deletion model, the AUCs were 0.80-0.86 in the internal and external validation sets. The decision curves show that both prediction models had good net benefits.
CONCLUSION
The prediction models which basing on VASARI and clinical features provided a reliable and clinically meaningful preoperative prediction for IDH and CDKN2A/B status in diffuse glioma patients. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalised treatment approaches for adult-type diffuse glioma patients.
PubMed: 38944632
DOI: 10.1016/j.acra.2024.06.020 -
International Journal of Biological... Jun 2024This study investigates the potential applications of incorporating 2D bacterial cellulose microfibers (BCM) biochar into chitosan/polyethyleneimine beads as a...
This study investigates the potential applications of incorporating 2D bacterial cellulose microfibers (BCM) biochar into chitosan/polyethyleneimine beads as a semi-natural sorbent for the efficient removal of tetracycline (TET) and metronidazole (MET) antibiotics. Batch adsorption experiments and characterization techniques evaluate removal performance and synthesized adsorbent properties. The adsorbent eliminated 99.13 % and 90 % of TET and MET at a 10 mg.L concentration with optimal pH values of 8 and 6, respectively, for 90 min. Under optimum conditions and a 400 mg.L concentration, MET and TET have possessed the maximum adsorption capacities of 691.325 and 960.778 mg.g, respectively. According to the isothermal analysis, the adsorption of TET fundamentally follows the Temkin (R = 0.997), Redlich-Peterson (R = 0.996), and Langmuir (R = 0.996) models. In contrast, the MET adsorption can be described by the Langmuir (R = 0.997), and Toth (R = 0.991) models. The pseudo-second-order (R = 0.998, 0.992) and Avrami (R = 0.999, 0.999) kinetic models were well-fitted with the kinetic results for MET and TET respectively. Diffusion models recommend that pore, liquid-film, and intraparticle diffusion govern the rate of the adsorption process. The developed semi-natural sorbent demonstrated exceptional adsorption capacity over eleven cycles due to its porous bead structure, making it a potential candidate for wastewater remediation.
PubMed: 38944566
DOI: 10.1016/j.ijbiomac.2024.132953 -
Magnetic Resonance Imaging Clinics of... Aug 2024Over the last 20 years, there have been remarkable developments in fetal brain MR imaging analysis methods. This article delves into the specifics of structural... (Review)
Review
Over the last 20 years, there have been remarkable developments in fetal brain MR imaging analysis methods. This article delves into the specifics of structural imaging, diffusion imaging, functional MR imaging, and spectroscopy, highlighting the latest advancements in motion correction, fetal brain development atlases, and the challenges and innovations. Furthermore, this article explores the clinical applications of these advanced imaging techniques in comprehending and diagnosing fetal brain development and abnormalities.
Topics: Humans; Brain; Pregnancy; Magnetic Resonance Imaging; Prenatal Diagnosis; Female; Neuroimaging; Fetus
PubMed: 38944434
DOI: 10.1016/j.mric.2024.03.004 -
Journal of Theoretical Biology Jun 2024The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a...
The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing the finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.
PubMed: 38944380
DOI: 10.1016/j.jtbi.2024.111893