Hosam Elessawy, Omar F. Abdul‐Rasheed, Mohammed F. Alqanbar
Background: Bladder cancer (BC) ranks as the tenth most common cancer globally, with a high recurrence rate. It is primarily caused by abnormalities in the epithelial layer lining the bladder and is classified from non-muscle invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC). Fibroblast Growth Factor Receptor 3 (FGFR3) S249C mutation is frequently observed in low-grade NMIBC but are rare in high-grade NMIBC and MIBC, leading to continuous receptor activation and promoting tumor growth.
Objective: This study aims to investigate the prevalence of FGFR3 S249C mutation in Iraqi BC patients, assess their association with tumor stage and grade, evaluate the potential of FGFR3 mutation as an early-stage diagnostic marker, and discuss implications for public health policy.
Subjects and Methods: The study was conducted at Al-Safeer Hospital, Karbala, Iraq. It included 60 individuals diagnosed with urothelial BC (50 males, 83.3%; 10 females, 16.4%) with a median age of 63 years. Tumor tissue samples from patients undergoing Transurethral Resection of Bladder Tumor (TURBT) were used. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples, and FGFR3 mutations were examined through direct DNA sequencing, focusing on the S249C mutation in exon 7. The prevalence of the S249C mutation was analyzed in relation to tumor stage and grade.
Results: The study revealed a significant prevalence (55%) of the S249C mutation. This mutation was more frequent among males and individuals over the age of 50 years. There was a higher incidence of BC in males (83.3%) compared to females (16.7%), especially in those aged 50 years and older. Histomorphological evaluations showed a considerable number of tumors classified as low-grade. Furthermore, pathological staging results identified pT1 as the most common stage, followed by pTa and pT2, underscoring the predominance of early-stage tumors within the study population.
Conclusions: This study highlighted the significant prevalence of FGFR3 S249C mutation in Iraqi BC patients. FGFR3 mutations were strongly associated with early-stage and low-grade tumors, indicating their potential as a molecular marker for early diagnosis.
Helena Torpy, The Huong Chau, Sayantani Chatterjee
et al.
The morbidity and mortality of sepsis remain high. Clinicians lack effective markers to rapidly diagnose sepsis and identify the underlying pathogen infection particularly for patients with candidaemia or cases of culture-negative sepsis where culture-based diagnostics are inadequate. In our search for new lines of potential sepsis biomarkers, we here explore the impact of various classes of infectious agents on the serum N-glycome in a septic shock cohort. Comparative N-glycomics was performed on sera collected from 49 septic shock patients infected with viral (n = 9), bacterial (n = 37) or fungal (n = 3) pathogens using an established PGC-LC-MS/MS method. Aberrant serum N-glycosylation features were observed in patients with fungal infection relative to the other infection sub-groups including i) altered expression of prominent α2,6-sialylated biantennary N-glycan isomers, ii) elevated levels of IgG-type N-glycosylation and iii) a global shift in the serum N-glycome involving altered glycan type distribution and considerable changes in core fucosylation and α2,6-sialylation. Septic shock patients infected with bacterial and viral pathogens exhibited similar global serum N-glycome features and therefore could not be stratified based on their serum N-glycosylation. Subtle and less consistent serum N-glycome differences were observed between septic shock patients infected with different bacterial pathogens. In conclusion, our study has tested the impact of different pathogen classes on the serum N-glycome in a septic shock cohort, and reports that fungal infection impacts the host serum N-glycome differently compared to bacterial or viral infections thus potentially opening avenues for glycan-based biomarkers to better diagnose patients with candidaemia.
Livhuwani E. Nephale, Ngonidzashe A.G. Moyo, Mmaditshaba M. Rapatsa-Malatji
An 8-week feeding trial was conducted to evaluate the effect of Alates termite (Macrotermes falciger) based diet in a herbivorous (Oreochromis mossambicus) and an opportunistic predator (Clarias gariepinus). Five diets were formulated to replace fishmeal at 0, 10, 30, 50, and 70 % and were denoted D1, D2, D3, D4, and D5, respectively. Clarias gariepinus sub-adults (209.24 ± 2.41 g/fish) were stocked at 5 fish per tank in recirculating fibreglass tanks (400 L) in triplicates. Oreochromis mossambicus juveniles (7.4 ± 4.78 g/fish) were randomly stocked at 10 fish per tank in recirculating fibreglass tanks (400 L) in triplicates. Fish were fed their allocated diets, twice a day to apparent satiation. Growth performance indices (specific growth rate, thermal-unit growth coefficient) were lowest at inclusion level above 50 % in both species (P < 0.05). The nutrient utilization indices (feed intake, protein efficiency ratio) were lowest at inclusion level above 50 % in both species. The organosomatic indices (condition factor, hepato-somatic index, viscero-somatic index) were not influenced by the inclusion of Alates termite meal in both species. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were not influenced by Alates termite meal in O. mossambicus (P > 0.05). However, AST and ALT levels significantly increased at inclusion levels above 50 % in C. gariepinus (P < 0.05). The triglyceride, cholesterol, and glucose levels showed no significant difference across diets in both fish species (P > 0.05). The study showed that both species may utilize an insect-based diet up to 50 % inclusion levels without adverse effects on growth performance and nutrient utilization.
Isaac D. Juárez, Isaac D. Juárez, Tianyi Dou
et al.
Rice (Oryza sativa) is the primary crop for nearly half of the world’s population. Groundwater in many rice-growing parts of the world often has elevated levels of arsenite and arsenate. At the same time, rice can accumulate up to 20 times more arsenic compared to other staple crops. This places an enormous amount of people at risk of chronic arsenic poisoning. In this study, we investigated whether Raman spectroscopy (RS) could be used to diagnose arsenic toxicity in rice based on biochemical changes that were induced by arsenic accumulation. We modeled arsenite and arsenate stresses in four different rice cultivars grown in hydroponics over a nine-day window. Our results demonstrate that Raman spectra acquired from rice leaves, coupled with partial least squares-discriminant analysis, enabled accurate detection and identification of arsenic stress with approximately 89% accuracy. We also performed high-performance liquid chromatography (HPLC)-analysis of rice leaves to identify the key molecular analytes sensed by RS in confirming arsenic poisoning. We found that RS primarily detected a decrease in the concentration of lutein and an increase in the concentration of vanillic and ferulic acids due to the accumulation of arsenite and arsenate in rice. This showed that these molecules are detectable indicators of biochemical response to arsenic accumulation. Finally, a cross-correlation of RS with HPLC and ICP-MS demonstrated RS’s potential for a label-free, non-invasive, and non-destructive quantification of arsenic accumulation in rice.
Annisa Alifia, Sri Mulyati, Wurlina Wurlina
et al.
This study aims to determine the effect of the administration of white guava (Psidium guajava L.) fruit juice on spermatozoa plasma membrane integrity (PMI), morphological abnormality, viability, and motility of lead acetate induced rats (Rattus norvegicus). Twenty-five male rats were divided into five groups: NC (negative control) group, rats were administered with distilled water twice daily at four-hour intervals; T0 (positive control) group, rats were administered daily with lead acetate 50 mg/kg bw and distilled water four hours later; T1, T2, and T3 groups, rats were administered daily with lead acetate 50 mg/kg bw and 0.5 mL of 25, 50, and 100% white guava fruit juice four hours later. The treatment of the rats was conducted for 14 days, and on day 15, all rats were sacrificed to assess the spermatozoa quality. Data was analyzed using ANOVA followed by Duncan's multiple range test at a confidence level of 95%. The results showed that exposure to lead acetate (T0) caused lower spermatozoa PMI, viability, and motility as well as higher spermatozoa morphological abnormalities (p <0.05) compared to those of the T0 group. Administration of white guava fruit juice starting at a dose of 25% (T1) resulted in higher spermatozoa motility, viability, and PMI as well as lower spermatozoa morphological abnormalities (p <0.05) compared to rats in the T0 group. It could be concluded that white guava fruit juice maintained the spermatozoa quality of lead acetate induced rats.
Abstract Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease caused by inhalation of cigarette smoke (CS) and other harmful gases and particles. Methods This study aimed to explore potential urinary biomarkers for CS-induced COPD based on LC–MS/MS analysis. Results A total of 340 urinary proteins were identified, of which 79 were significantly changed (30, 31, and 37 at week 2, 4 and 8, respectively). GO annotation of the differential urinary proteins revealed that acute-phase response, response to organic cyclic compounds, complement activation classical pathway, and response to lead ion were significantly enriched at week 2 and 4. Another four processes were only enriched at week 8, namely response to oxidative stress, positive regulation of cell proliferation, thyroid hormone generation, and positive regulation of apoptotic process. The PPI network indicated that these differential proteins were biologically connected in CS-exposed rats. Of the 79 differential proteins in CS-exposed rats, 56 had human orthologs. Seven proteins that had changed at week 2 and 4 when there were no changes of pulmonary function and pathological morphology were verified as potential biomarkers for early screening of CS-induced COPD by proteomic analysis. Another six proteins that changed at week 8 when obvious airflow obstruction was detected were verified as potential biomarkers for prognostic assessment of CS-induced COPD. Conclusions These results reveal that the urinary proteome could sensitively reflect pathological changes in CS-exposed rats, and provide valuable clues for exploring COPD biomarkers.
The increasing availability and use of POCT are influenced by many factors, including the industry trend toward patient-centered care and decentralization of health care; the increasing prevalence of infectious diseases, which includes the current use of rapid SARS-CoV-2 testing; the increasing incidence of lifestyle diseases such as diabetes, heart disease, and hypertension; and advances in in-vitro medical diagnostics. The use of POCT can increase the efficiency of services and improve patient outcomes. However, the variability of the testing environment and conditions, as well as the competency of the staff performing the tests, can have a significant impact on the quality and accuracy of POCT results. Most personnel performing POCT are not trained laboratory staff and may not be as familiar with the processes associated with testing, such as patient preparation, specimen collection, management of equipment and supplies, calibration and maintenance of equipment, the performance of the test, quality control, interpretation of results, and reporting/documentation of results related to the particular patient. Therefore, personnel performing POCT must have the appropriate training and experience to ensure that test results are accurate and reliable. This review outlines the specific personnel training requirements based on international standards that must be considered to ensure the quality of test results and describe the competency criteria required for POCT compliance.
Soichiro Hoshino, Ryohei Kanemura, Daisuke Kurita
et al.
Hoshino et al. show that PTH3, the S. cerevisiae homolog of C12orf65, is required for the translation of mitochondrial genes in the presence of antibiotics. This study suggests that PTH3 rescues the ribosomes stalled by antibiotics, playing a role in antibiotic resistance in fungi.
Jovanović Ljiljana, Subota Vesna, Stavrić Milena
et al.
Background/Aim. The evaluation of blood levels of cardiac troponin I (cTnI), D-dimer, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) on admission and during the treatment of pulmonary embolism (PE) are the part of routine diagnostic process and estimation of mortality risk. The aim of this study was to evaluate the predictive value of these biomarkers on admission for all-cause 30-day mortality in consecutive PE patients regarding whether they classified as spontaneous, transiently provoked, or permanently provoked PE. Methods. This retrospective analysis was gained from the data of 590 PE patients from the Serbian University Multicenter Pulmonary Embolism Registry (SUPER). Patients had at least one of these biomarkers (BNP, CRP, cTnI, and D-dimer) measured during the first 24 hours upon admission. Results. Receiver operating characteristic (ROC) curve analyses demonstrated that BNP had the highest prognostic accuracy for 30-day mortality in patients (n = 219) who had data for all examined biomarkers. BNP provided an AUC of 0.785 (p < 0.001). Separately, BNP had the highest c-statistic for all three groups of patients. CRP had a modest predictive value for the 30-day all-cause mortality in the group with transient provoked PE. Troponin I had a very modest predictive value for the 30-day all-cause mortality only in patients with spontaneous PE, and D-dimer was a very weak predictor of this end-point only in patients with persistent provoked PE. Conclusion. Patients with spontaneous, transient provoked, and persistent provoked PE have a significantly different pro-file of blood biomarkers level with different prognostic significance for early all-cause mortality.
Rachael Mooney, Wafa Abidi, Jennifer Batalla-Covello
et al.
Abstract Background Immortalized, clonal HB1.F3.CD 21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored. Methods To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies. Results Here, we report efficient tumor tropism of HB1.F3.CD 21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 h after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting. Conclusions Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.
Laura Pandolfi, Sara Bozzini, Vanessa Frangipane
et al.
The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs that correlates with neutrophils count; moreover, the analysis of lung tissues of COVID-19 deceased patients showed a subset of alveolar reactive pneumocytes with a co-expression of epithelial marker and a mesenchymal marker, confirming the induction of EMT mechanism after severe SARS-CoV2 infection. By airway in vitro models, cultivating A549 or 16HBE at air-liquid interface, adding alveolar macrophages (AM), neutrophils and SARS-CoV2, we demonstrated that to trigger a complete EMT expression pattern are necessary the induction of NETosis by SARS-CoV2 and the secretion of AM factors (TGF-β, IL8 and IL1β). All our results highlight the possible mechanism that can induce lung fibrosis after SARS-CoV2 infection.
Ibrahim Hassan, Wan Norhamidah Wan Ibrahim, Ferdaus Mohamat Yusuf
et al.
Background. Pathophysiological changes leading to the death of nerve cells present in the brain and spinal cord are referred to as neurodegenerative diseases. Presently, treatment of these diseases is not effective and encounters many challenges due to the cost of drug and side effects. Thus, the search for the alternative agents to replace synthetic drugs is in high demand. Therefore, the aim of this study is to evaluate the anticholinesterase properties of Ginkgo biloba seed. Methods. The seed was extracted with 80% methanol. Toxicity studies and evaluation of anticholinesterase activities were carried out in adult Javanese medaka (Oryzias javanicus). Phytochemical study to identify the bioactive lead constituents of the crude extract was also carried out using high performance liquid chromatography (HPLC). Results. The result shows activities with high significant differences at P<0.001 between the treated and nontreated groups. A bioactive compound (vitaxin) was identified with the aid of HPLC method. Conclusion. The presence of bioactive compound vitaxin is among the major secondary metabolites that contribute to increasing activities of this plant extract. High anticholinesterase activities and low toxicity effect of this plant show its benefit to be used as natural medicine or supplements.