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IET Systems Biology Jun 2024Genes associated with endoplasmic reticulum stress (ERS) and mitophagy can be conducive to predicting solid tumour prognosis. The authors aimed to develop a prognosis...
Genes associated with endoplasmic reticulum stress (ERS) and mitophagy can be conducive to predicting solid tumour prognosis. The authors aimed to develop a prognosis prediction model for these genes in lung adenocarcinoma (LUAD). Relevant gene expression and clinical information were collected from public databases including Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 265 differentially expressed genes was finally selected (71 up-regulated and 194 downregulated) in the LUAD dataset. Among these, 15 candidate ERS and mitophagy genes (ATG12, CSNK2A1, MAP1LC3A, MAP1LC3B, MFN2, PGAM5, PINK1, RPS27A, SQSTM1, SRC, UBA52, UBB, UBC, ULK1, and VDAC1) might be critical to LUAD based on the expression analysis after crossing with the ERS and mitochondrial autophagy genes. The prediction model demonstrated the ability to effectively predict the 5-, 3-, and 1-year prognoses of LUAD patients in both GEO and TCGA databases. Moreover, high VDAC1 expression was associated with poor overall survival in LUAD (p < 0.001), suggesting it might be a critical gene for LUAD prognosis prediction. Overall, the prognosis model based on ERS and mitophagy genes in LUAD can be useful for evaluating the prognosis of patients with LUAD, and VDAC1 may serve as a promising biomarker for LUAD prognosis.
Topics: Humans; Mitophagy; Endoplasmic Reticulum Stress; Prognosis; Adenocarcinoma of Lung; Lung Neoplasms; Voltage-Dependent Anion Channel 1; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Gene Expression Profiling; Transcriptome
PubMed: 38813617
DOI: 10.1049/syb2.12092 -
Turkish Journal of Medical Sciences 2024Male infertility rises for many reasons, along with age; therefore, we aimed to research the characterization of aquaporin-3, 7, and 8 in human sperm belonging to...
BACKGROUND/AIM
Male infertility rises for many reasons, along with age; therefore, we aimed to research the characterization of aquaporin-3, 7, and 8 in human sperm belonging to different age groups.
MATERIAL AND METHODS
This study was conducted on sperm samples of men aged over 18 years. A total of 60 men were included in the study and divided into three age groups: group 1, age 18-25 years (n = 20); group 2, age 26-35 years (n = 20); and group 3, age ≥35 years (n = 20). Sperm ejaculates obtained from each participant were used for spermiogram tests, Kruger strict morphology analysis, and immunohistochemistry.
RESULTS
We observed no statistically significant differences in terms of macroscopic and microscopic sperm testing. The immunostaining score of aquaporin-3 was the lowest in group 1 and increased in group 3 and group 2, respectively (p < 0.05). Aquaporin-8 immunostaining only increased in group 2 (p < 0.05). Aquaporin-7 immunostaining scores were not different between the groups (p > 0.05). When the immunostaining scores of aquaporin molecules were compared with each other, aquaporin-7 was significantly increased compared with the others (p < 0.05).
CONCLUSION
According to the results, it can be stated that aquaporin-3 and aquaporin-8 molecules were more expressed at age 26 to 35 years, and aquaporin-7 was densely expressed from age 18 to 25 years. If the characterization of these molecules is adversely affected, male infertility may eventually emerge. We recommend further advanced-level studies on this subject.
Topics: Humans; Male; Adult; Aquaporins; Spermatozoa; Young Adult; Adolescent; Aquaporin 3; Infertility, Male; Age Factors; Immunohistochemistry; Semen Analysis
PubMed: 38812647
DOI: 10.55730/1300-0144.5781 -
Turkish Journal of Medical Sciences 2024Nocturnal enuresis can be frustrating for children and their families as the child ages. Our aim is to evaluate urine aquaporin 2 (AQP-2) as a noninvasive biomarker of...
BACKGROUND/AIM
Nocturnal enuresis can be frustrating for children and their families as the child ages. Our aim is to evaluate urine aquaporin 2 (AQP-2) as a noninvasive biomarker of water balance in children with primary monosymptomatic nocturnal enuresis (PMNE).
MATERIAL AND METHODS
The study included 90 children; sixty-eight children suffering from PMNE aged (9.57 ± 2.16) years and 22 healthy children with good toilet control, matched sex and age. All enuretic children were subjected to complete history taking, clinical evaluation, and bed wetting diary. Serum arginine vasopressin (AVP) and urine AQP-2 were tested in the morning (at 9-11 am) and evening (at 9-11 pm). Blood urea, creatinine, Na, glucose, urine osmolality, Ca/Cr, Alb/Cr and specific gravity were tested simultaneously.
RESULTS
Serum AVP, urine AQP-2, and urine osmolality were statistically lower in patients than controls. Patients had a significantly lower level of night serum AVP concentrations, urine AQP-2, and urine osmolality than the corresponding morning level. Urine AQP-2 was significantly correlated with urine osmolality (p < 0.05). AQP-2 had a sensitivity of 90% and a specificity of 70%. However, no statistically significant correlation was found between serum AVP and urine AQP-2.
CONCLUSION
Primary monosymptomatic nocturnal enuresis in children could be associated with reduction of urine excretion of AQP-2 at night. Urine AQP-2 is significantly correlated with urine osmolality. Therefore, it may be a noninvasive biomarker of hydration status in children with PMNE, with good sensitivity and specificity.
Topics: Humans; Child; Nocturnal Enuresis; Male; Female; Aquaporin 2; Circadian Rhythm; Biomarkers; Osmolar Concentration; Case-Control Studies; Arginine Vasopressin; Adolescent
PubMed: 38812639
DOI: 10.55730/1300-0144.5780 -
Journal of Bacteriology Jun 2024The EnvZ-OmpR two-component system of regulates the expression of the and porin genes in response to medium osmolarity. However, certain mutations in confer...
The EnvZ-OmpR two-component system of regulates the expression of the and porin genes in response to medium osmolarity. However, certain mutations in confer pleiotropy by affecting the expression of genes of the iron and maltose regulons not normally controlled by EnvZ-OmpR. In this study, we obtained two novel and pleiotropic alleles, and , among revertants of a mutant with heightened envelope stress and an outer membrane (OM) permeability defect. Unlike , pleiotropic mutations in have not been described previously. The mutant alleles reduced the expression of several outer membrane proteins (OMPs), overcame the temperature-sensitive growth defect of a protease-deficient (Δ) strain, and lowered envelope stress and OM permeability defects in a background lacking the BamB protein of an essential β-barrel assembly machinery complex. Biochemical analysis showed OmpRL19Q, like wild-type OmpR, is readily phosphorylated by EnvZ, but the EnvZ-dependent dephosphorylation of OmpRL19Q~P was drastically impaired compared to wild-type OmpR. This defect would lead to a prolonged half-life for OmpRL19Q~P, an outcome remarkably similar to what we had previously described for EnvZR397L, resulting in pleiotropy. By employing null alleles of the OMP genes, it was determined that the three pleiotropic alleles lowered envelope stress by reducing OmpF and LamB levels. The absence of LamB was principally responsible for lowering the OM permeability defect, as assessed by the reduced sensitivity of a Δ mutant to vancomycin and rifampin. Possible mechanisms by which novel EnvZ and OmpR mutants influence EnvZ-OmpR interactions and activities are discussed.IMPORTANCEMaintenance of the outer membrane (OM) integrity is critical for the survival of Gram-negative bacteria. Several envelope homeostasis systems are activated when OM integrity is perturbed. Through the isolation and characterization of novel pleiotropic / alleles, this study highlights the involvement of the EnvZ-OmpR two-component system in lowering envelope stress and the OM permeability defect caused by the loss of proteins that are involved in OM biogenesis, envelope homeostasis, and structural integrity.
Topics: Escherichia coli Proteins; Escherichia coli; Gene Expression Regulation, Bacterial; Bacterial Outer Membrane Proteins; Anti-Bacterial Agents; Alleles; Bacterial Proteins; Porins; Mutation; Stress, Physiological; Phosphorylation; Multienzyme Complexes; Trans-Activators
PubMed: 38809006
DOI: 10.1128/jb.00172-24 -
Human Cell Jul 2024Aquaporins (AQPs) are small, integral proteins facilitating water transport across plasma cell membranes in response to osmotic gradients. This family has 13 unique... (Review)
Review
Aquaporins (AQPs) are small, integral proteins facilitating water transport across plasma cell membranes in response to osmotic gradients. This family has 13 unique members (AQP0-12), which can also transport glycerol, urea, gases, and other salute small molecules. AQPs play a crucial role in the regulation of different cellular processes, including metabolism, migration, immunity, barrier function, and angiogenesis. These proteins are found to aberrantly overexpress in various cancers, including colorectal cancer (CRC). Growing evidence has explored AQPs as a potential diagnostic biomarker and therapeutic target in different cancers. However, there is no comprehensive review compiling the available information on the crucial role of AQPs in the context of colorectal cancer. This review highlights the significance of AQPs as the biomarker and regulator of tumor cells metabolism. In addition, the proliferation, angiogenesis, and metastasis of tumor cells related to AQPs expression as well as function are discussed. Understanding the AQPs prominent role in chemotherapy resistance is of great importance clinically.
Topics: Humans; Colorectal Neoplasms; Aquaporins; Carcinogenesis; Drug Resistance, Neoplasm; Neoplasm Metastasis; Neovascularization, Pathologic; Biomarkers, Tumor; Cell Proliferation; Gene Expression; Molecular Targeted Therapy
PubMed: 38806940
DOI: 10.1007/s13577-024-01078-7 -
Journal of Neuroinflammation May 2024Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our...
Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.
Topics: Animals; Mice; Aquaporin 4; Astrocytes; Hyperammonemia; Sepsis-Associated Encephalopathy; Male; Brain-Gut Axis; Mice, Inbred C57BL; Ammonia; Brain; Fecal Microbiota Transplantation
PubMed: 38802927
DOI: 10.1186/s12974-024-03135-2 -
Brain : a Journal of Neurology Jun 2024Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic...
Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.
Topics: Adult; Aged; Animals; Female; Humans; Male; Mice; Middle Aged; Aquaporin 4; Blast Injuries; Brain Concussion; Brain Injuries, Traumatic; Frontal Lobe; Glymphatic System; Magnetic Resonance Imaging; Mice, Inbred C57BL; Veterans
PubMed: 38802114
DOI: 10.1093/brain/awae065 -
Microbial Biotechnology May 2024Pseudomonas aeruginosa is a notorious multidrug-resistant pathogen that poses a serious and growing threat to the worldwide public health. The expression of resistance... (Review)
Review
Pseudomonas aeruginosa is a notorious multidrug-resistant pathogen that poses a serious and growing threat to the worldwide public health. The expression of resistance determinants is exquisitely modulated by the abundant regulatory proteins and the intricate signal sensing and transduction systems in this pathogen. Downregulation of antibiotic influx porin proteins and upregulation of antibiotic efflux pump systems owing to mutational changes in their regulators or the presence of distinct inducing molecular signals represent two of the most efficient mechanisms that restrict intracellular antibiotic accumulation and enable P. aeruginosa to resist multiple antibiotics. Treatment of P. aeruginosa infections is extremely challenging due to the highly inducible mechanism of antibiotic resistance. This review comprehensively summarizes the regulatory networks of the major porin proteins (OprD and OprH) and efflux pumps (MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY) that play critical roles in antibiotic influx and efflux in P. aeruginosa. It also discusses promising therapeutic approaches using safe and efficient adjuvants to enhance the efficacy of conventional antibiotics to combat multidrug-resistant P. aeruginosa by controlling the expression levels of porins and efflux pumps. This review not only highlights the complexity of the regulatory network that induces antibiotic resistance in P. aeruginosa but also provides important therapeutic implications in targeting the inducible mechanism of resistance.
Topics: Pseudomonas aeruginosa; Anti-Bacterial Agents; Gene Expression Regulation, Bacterial; Humans; Membrane Transport Proteins; Pseudomonas Infections; Drug Resistance, Multiple, Bacterial; Porins; Bacterial Proteins; Biological Transport
PubMed: 38801351
DOI: 10.1111/1751-7915.14487 -
Reproduction in Domestic Animals =... May 2024Present study was designed to evaluate the role of virulence factor genes (papG, cnf1 and hylA) in the pathogenesis of canine pyometra. Antimicrobial susceptibility test...
Present study was designed to evaluate the role of virulence factor genes (papG, cnf1 and hylA) in the pathogenesis of canine pyometra. Antimicrobial susceptibility test and detection of virulence genes were performed Escherichia coli (E. coli) detected in uterine swab samples. Animals were divided into two groups based on the presence (VF+, n:14) or absence (VF-, n:7) of the virulence factor genes papG, cnf1 and hylA. Blood and tissue glutathione peroxidase activity, uterine histopathologic analysis and AQP3, ESR1, PGR, OXTR gene expressions were determined in both groups. Statistical analyses were performed using Stata version 15.1. All E. coli isolates were susceptible to amikacin, whereas resistant to ampicillin, amoxicillin/clavulanic acid and lincomycin. None of the isolates were susceptible to cefotaxime. E. coli isolates had at least one virulence gene. The most prevalent gene was fimH (100%), followed by fyuA (95.8%), usp (83.3%), sfa (75%), cnf1 and hlyA (70.8%) genes. Blood GPx activity was greater in VF+ animals. On the other hand, uterine tissue GPx activity was lower in VF+ group compared to the control group. Expression levels of AQP3 were upregulated more than fivefold in VF-dogs compared to the control group. In addition, AQP3 expression levels were found approximately threefold higher in VF (-) than VF (+) group (p < .05). Varying degree of inflammation noted for all animals with pyometra, but the presence of bacteria noted only in VF+ animals. In conclusion, the presence of virulence factor genes does not play a role in the histopathological degree of inflammation, the presence of bacteria was found to vary. Serum GPx activity increased in VF+ animals. While the hormone receptor expressions were similar, AQP expression was upregulated in the absence of virulence factor genes.
Topics: Animals; Female; Virulence Factors; Aquaporin 3; Dogs; Pyometra; Dog Diseases; Uterus; Escherichia coli; Glutathione Peroxidase; Escherichia coli Infections; Anti-Bacterial Agents; Down-Regulation; Microbial Sensitivity Tests
PubMed: 38798181
DOI: 10.1111/rda.14615 -
European Journal of Pharmacology Aug 2024Ischemia/reperfusion is a pathological condition by the restoration of perfusion and oxygenation following a period of restricted blood flow to an organ. To address...
INTRODUCTION
Ischemia/reperfusion is a pathological condition by the restoration of perfusion and oxygenation following a period of restricted blood flow to an organ. To address existing uncertainty in the literature regarding the effects of 3', 4'-dihydroxy flavonol (DiOHF) on cerebral ischemia/reperfusion injury, our study aims to investigate the impact of DiOHF on neurological parameters, apoptosis (Caspase-3), aquaporin 4 (AQP4), and interleukin-10 (IL-10) levels in an experimental rat model of brain ischemia-reperfusion injury.
MATERIALS/METHODS
A total of 28 Wistar-albino male rats were used in this study. Experimental groups were formed as 1-Control, 2-Sham, 3-Ischemia-reperfusion, 4-Ischemia-reperfusion + DiOHF (10 mg/kg). The animals were anaesthetized, and the carotid arteries were ligated (ischemia) for 30 min, followed by reperfusion for 30 min. Following reperfusion, DiOHF was administered intraperitoneally to the animals at a dose of 10 mg/kg for 1 week. During the one-week period neurological scores and new object recognition tests were performed. Then, caspase 3 and AQP4 levels were determined by PCR method and IL-10 by ELISA method in hippocampus tissue samples taken from animals sacrificed under anaesthesia.
RESULTS
Brain ischemia reperfusion significantly increased both caspase 3 and AQP4 values in the hippocampus tissue, while decreasing IL-10 levels. However, 1-week DiOHF supplementation significantly suppressed increased caspase 3 and AQP4 levels and increased IL-10 values. While I/R also increased neurological score values, it suppressed the ability to recognize new objects, and the administered treatment effectively ameliorated the adverse effects observed, resulting in a positive outcome.
CONCLUSIONS
The results of the study show that brain ischemia caused by bilateral carotid occlusion in rats and subsequent reperfusion causes tissue damage, but 1-week DiOHF application has a healing effect on both hippocampus tissue and neurological parameters.
Topics: Animals; Male; Reperfusion Injury; Flavonols; Rats, Wistar; Rats; Cognition; Caspase 3; Aquaporin 4; Interleukin-10; Neuroprotective Agents; Hippocampus; Neurons; Brain Ischemia; Disease Models, Animal; Apoptosis
PubMed: 38795755
DOI: 10.1016/j.ejphar.2024.176670