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BMC Veterinary Research Jun 2024Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant...
BACKGROUND
Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant metastasis, thereby improving overall survival rates. While acquiring molecular data before surgery offers significant potential benefits, the current protein biomarkers for monitoring disease progression in non-metastatic FMC (NmFMC) and metastatic FMC (mFMC) are limited. The objective of this study was to investigate the serum peptidome profiles of NmFMC and mFMC using liquid chromatography-tandem mass spectrometry. A cross-sectional study was conducted to compare serum peptidome profiles in 13 NmFMC, 23 mFMC and 18 healthy cats. The liquid chromatography-tandem mass spectrometry analysis was performed on non-trypsinized samples.
RESULTS
Out of a total of 8284 expressed proteins observed, several proteins were found to be associated with human breast cancer. In NmFMC, distinctive protein expressions encompassed double-stranded RNA-binding protein Staufen homolog 2 (STAU2), associated with cell proliferation, along with bromodomain adjacent to zinc finger domain 2A (BAZ2A) and gamma-aminobutyric acid type A receptor subunit epsilon (GABRE), identified as potential treatment targets. Paradoxically, positive prognostic markers emerged, such as complement C1q like 3 (C1QL3) and erythrocyte membrane protein band 4.1 (EPB41 or 4.1R). Within the mFMC group, overexpressed proteins associated with poor prognosis were exhibited, including B-cell lymphoma 6 transcription repressor (BCL6), thioredoxin reductase 3 (TXNRD3) and ceruloplasmin (CP). Meanwhile, the presence of POU class 5 homeobox (POU5F1 or OCT4) and laminin subunit alpha 1 (LAMA1), reported as metastatic biomarkers, was noted.
CONCLUSION
The presence of both pro- and anti-proliferative proteins was observed, potentially indicating a distinctive characteristic of NmFMC. Conversely, proteins associated with poor prognosis and metastasis were noted in the mFMC group.
Topics: Animals; Female; Cat Diseases; Cats; Tandem Mass Spectrometry; Mammary Neoplasms, Animal; Biomarkers, Tumor; Chromatography, Liquid; Cross-Sectional Studies; Neoplasm Metastasis; Proteomics
PubMed: 38951817
DOI: 10.1186/s12917-024-04148-y -
Lipids in Health and Disease Jun 2024Glycerophospholipids (GPLs) are essential for cell membrane structure and function. Sphingomyelin and its metabolites regulate cell growth, apoptosis, and stress...
BACKGROUND
Glycerophospholipids (GPLs) are essential for cell membrane structure and function. Sphingomyelin and its metabolites regulate cell growth, apoptosis, and stress responses. This study aimed to investigate lipid metabolism in patients experiencing sudden sensorineural hearing loss across all frequencies (AF-SSNHL).
METHODS
The study included 60 patients diagnosed with unilateral AF-SSNHL, among whom 30 patients had a level of hearing improvement ≥ 15 dB after 6 months of follow-up. A propensity score-matched (2:1) control group was used. Liquid chromatography‒mass spectrometry based untargeted lipidomics analysis combined with multivariate statistics was performed to investigate the lipids change. The "lipidome" R package and weighted gene co-expression network analysis (WGCNA) were utilised to assess the lipids' structural features and the association between lipids and hearing.
RESULTS
Lipidomics successfully differentiated the AF-SSNHL group from the control group, identifying 17 risk factors, mainly including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and related metabolites. The ratios of lysophosphatidylcholine/PC, lysophosphatidylethanolamine/PE, and lysodimethylphosphatidylethanolamine/PE were upregulated, while some glycerophospholipid (GPL)-plasmalogens were downregulated in the AF-SSNHL group, indicating abnormal metabolism of GPLs. Trihexosylceramide (d34:1), PE (18:1e_22:5), and sphingomyelin (d40:3) were significantly different between responders and nonresponders, and positively correlated with hearing improvement. Additionally, the results of the WGCNA also suggested that partial GPL-plasmalogens were positively associated with hearing improvement.
CONCLUSION
AF-SSNHL patients exhibited abnormally high blood lipids and pronounced GPLs metabolic abnormalities. Sphingolipids and GPL-plasmalogens had an association with the level of hearing improvement. By understanding the lipid changes, clinicians may be able to predict the prognosis of hearing recovery and personalize treatment approaches.
Topics: Humans; Female; Male; Middle Aged; Biomarkers; Hearing Loss, Sensorineural; Lipid Metabolism; Lipidomics; Adult; Hearing Loss, Sudden; Glycerophospholipids; Aged; Phosphatidylethanolamines; Phosphatidylcholines; Lysophosphatidylcholines; Sphingomyelins; Lysophospholipids
PubMed: 38951804
DOI: 10.1186/s12944-024-02189-8 -
Nature Chemical Biology Jul 2024Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes are...
Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes are potential drug targets and valuable biotechnological tools for generating vaccine antigens. Despite their importance, it remains unknown how structurally variable capsule polymers of Gram-negative pathogens are linked to the conserved glycolipid anchoring these virulence factors to the bacterial membrane. Using Actinobacillus pleuropneumoniae as an example, we demonstrate that CpsA and CpsC generate a poly(glycerol-3-phosphate) linker to connect the glycolipid with capsules containing poly(galactosylglycerol-phosphate) backbones. We reconstruct the entire capsule biosynthesis pathway in A. pleuropneumoniae serotypes 3 and 7, solve the X-ray crystal structure of the capsule polymerase CpsD, identify its tetratricopeptide repeat domain as essential for elongating poly(glycerol-3-phosphate) and show that CpsA and CpsC stimulate CpsD to produce longer polymers. We identify the CpsA and CpsC product as a wall teichoic acid homolog, demonstrating similarity between the biosynthesis of Gram-positive wall teichoic acid and Gram-negative capsules.
PubMed: 38951648
DOI: 10.1038/s41589-024-01664-8 -
Scientific Reports Jul 2024Using 70 U/ml or 35 U/ml as CA125 routine abnormal threshold may result in omissions in the relapse detection of Ovarian cancer (OvCa). This study aimed to clarify the...
Using 70 U/ml or 35 U/ml as CA125 routine abnormal threshold may result in omissions in the relapse detection of Ovarian cancer (OvCa). This study aimed to clarify the association between a biochemical relapse (only the elevation of CA125) and an image-identified relapse to predict the relapsed lesions better. 162 patients who achieved complete clinical response were enrolled from women diagnosed with stage I-IV serous ovarian, tubal, and peritoneal cancers from January 2013 to June 2019 at our center. The CA125 level of 2 × nadir was defined as the indicator of image-identified relapse (P < 0.001). Compared to CA125 level exceeding 35 U/ml, the 2 × nadir of CA125 improve the sensitivity of image-identified relapse (84.9% vs 67.4%, P < 0.001); the 2 × nadir value can act as an earlier warning relapse signal with a longer median time to image-identified relapse (2.7 vs. 0 months, P < 0.001). Of the relapsed population, there was no difference of CA125 changing trend between the neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) group after initial treatment. Compared with 35 U/ml, CA125 reaching 2 × nadir during the follow-up process might be a more sensitive and early relapse signal in patients with serous OvCa. This criterion may help guide patients to be recommended for imaging examination to detect potential relapse in time.
Topics: Humans; Female; CA-125 Antigen; Middle Aged; Ovarian Neoplasms; Neoplasm Recurrence, Local; Aged; Adult; Cystadenocarcinoma, Serous; Biomarkers, Tumor; Neoadjuvant Therapy; Retrospective Studies; Membrane Proteins
PubMed: 38951620
DOI: 10.1038/s41598-024-65760-4 -
Scientific Reports Jul 2024In this study, composite electrodes with metal-organic framework (MOF) for brackish water desalination via capacitive deionization (CDI) were developed. The electrodes...
In this study, composite electrodes with metal-organic framework (MOF) for brackish water desalination via capacitive deionization (CDI) were developed. The electrodes contained activated carbon (AC), polyvinylidene fluoride (PVDF), and zinc-benzene tricarboxylic acid (Zn-BTC) MOF in varying proportions, improving their electrochemical performance. Among them, the E4 electrode with 6% Zn-BTC MOF exhibited the best performance in terms of CV and EIS analyses, with a specific capacity of 88 F g and low ion charge transfer resistance of 4.9 Ω. The E4 electrode showed a 46.7% increase in specific capacitance compared to the E1 electrode, which did not include the MOF. Physicochemical analyses, including XRD, FTIR, FESEM, BET, EDS, elemental mapping, and contact angle measurements, verified the superior properties of the E4 electrode compared to E1, showcasing successful MOF synthesis, desirable pore size, elemental and particle-size distribution of materials, and the superior hydrophilicity enhancement. By evaluating salt removal capacity (SRC) in various setups using an initially 100.0 mg L NaCl feed solution, the asymmetric arrangement of E1 and E4 electrodes outperformed symmetric arrangements, achieving a 21.1% increase in SRC to 6.3 mg g. This study demonstrates the potential of MOF-incorporated electrodes for efficient CDI desalination processes.
PubMed: 38951566
DOI: 10.1038/s41598-024-66023-y -
Nature Communications Jun 2024While light can affect emotional and cognitive processes of the medial prefrontal cortex (mPFC), no light-encoding was hitherto identified in this region. Here,...
While light can affect emotional and cognitive processes of the medial prefrontal cortex (mPFC), no light-encoding was hitherto identified in this region. Here, extracellular recordings in awake mice revealed that over half of studied mPFC neurons showed photosensitivity, that was diminished by inhibition of intrinsically photosensitive retinal ganglion cells (ipRGCs), or of the upstream thalamic perihabenular nucleus (PHb). In 15% of mPFC photosensitive neurons, firing rate changed monotonically along light-intensity steps and gradients. These light-intensity-encoding neurons comprised four types, two enhancing and two suppressing their firing rate with increased light intensity. Similar types were identified in the PHb, where they exhibited shorter latency and increased sensitivity. Light suppressed prelimbic activity but boosted infralimbic activity, mirroring the regions' contrasting roles in fear-conditioning, drug-seeking, and anxiety. We posit that prefrontal photosensitivity represents a substrate of light-susceptible, mPFC-mediated functions, which could be ultimately studied as a therapeutical target in psychiatric and addiction disorders.
Topics: Animals; Prefrontal Cortex; Light; Mice; Retinal Ganglion Cells; Male; Neurons; Mice, Inbred C57BL; Photic Stimulation; Action Potentials
PubMed: 38951486
DOI: 10.1038/s41467-024-49794-w -
Molecular and Cellular Biochemistry Jun 2024Despite the implementation of novel therapeutic regimens and extensive research efforts, chemoresistance remains a formidable challenge in the treatment of acute myeloid...
Despite the implementation of novel therapeutic regimens and extensive research efforts, chemoresistance remains a formidable challenge in the treatment of acute myeloid leukemia (AML). Notably, the involvement of lysosomes in chemoresistance has sparked interest in developing lysosome-targeted therapies to sensitize tumor cells to currently approved chemotherapy or as innovative pharmacological approaches. Moreover, as ion channels on the lysosomal membrane are critical regulators of lysosomal function, they present potential as novel targets for enhancing chemosensitivity. Here, we discovered that the expression of a lysosomal cation channel, namely transient receptor potential mucolipin 1 (TRPML1), was elevated in AML cells. Inhibiting TRPML1 individually does not impact the proliferation and apoptosis of AML cells. Importantly, inhibition of TRPML1 demonstrated the potential to modulate the sensitivity of AML cells to chemotherapeutic agents. Exploration of the underlying mechanisms revealed that suppression of TRPML1 impaired autophagy while concurrently increasing the production of reactive oxygen species (ROS) and ROS-mediated lipid peroxidation (Lipid-ROS) in AML cells. Finally, the knockdown of TRPML1 significantly reduced OCI-AML3 tumor growth following chemotherapy in a mouse model of human leukemia. In summary, targeting TRPML1 represents a promising approach for combination therapy aimed at enhancing chemosensitivity in treating AML.
PubMed: 38951379
DOI: 10.1007/s11010-024-05054-5 -
Archives of Microbiology Jul 2024Ionic liquids (ILs) are interesting chemical compounds that have a wide range of industrial and scientific applications. They have extraordinary properties, such as the...
Ionic liquids (ILs) are interesting chemical compounds that have a wide range of industrial and scientific applications. They have extraordinary properties, such as the tunability of many of their physical properties and, accordingly, their activities; and the ease of synthesis methods. Hence, they became important building blocks in catalysis, extraction, electrochemistry, analytics, biotechnology, etc. This study determined antifungal activities of various imidazolium-based ionic liquids against yeast Saccharomyces cerevisiae via minimum inhibitory concentration (MIC) estimation method. Increasing the length of the alkyl group attached to the imidazolium cation, enhanced the antifungal activity of the ILs, as well as their ability of the disruption of the cell membrane integrity. FTIR studies performed on the S. cerevisiae cells treated with the ILs revealed alterations in the biochemical composition of these cells. Interestingly, the alterations in fatty acid content occurred in parallel with the increase in the activity of the molecules upon the increase in the length of the attached alkyl group. This trend was confirmed by statistical analysis and machine learning methodology. The classification of antifungal activities based on FTIR spectra of S. cerevisiae cells yielded a prediction accuracy of 83%, indicating the pharmacy and medicine industries could benefit from machine learning methodology. Furthermore, synthesized ionic compounds exhibit significant potential for pharmaceutical and medical applications.
Topics: Saccharomyces cerevisiae; Ionic Liquids; Imidazoles; Antifungal Agents; Cell Membrane; Microbial Sensitivity Tests; Spectroscopy, Fourier Transform Infrared
PubMed: 38951200
DOI: 10.1007/s00203-024-04043-y -
Zhonghua Fu Chan Ke Za Zhi Jun 2024
Review
Topics: Humans; Polycystic Ovary Syndrome; Female; Mitochondria; Oocytes; Ovarian Follicle; DNA, Mitochondrial; Infertility, Female; Membrane Potential, Mitochondrial; Oxidative Stress; Reproductive Techniques, Assisted; Apoptosis
PubMed: 38951083
DOI: 10.3760/cma.j.cn112141-20240116-00039 -
The Journal of Neuroscience : the... Jul 2024At chemical synapses, voltage-gated Ca-channels (VGCCs) translate electrical signals into a trigger for synaptic vesicle (SV) fusion. VGCCs and the Ca microdomains they...
At chemical synapses, voltage-gated Ca-channels (VGCCs) translate electrical signals into a trigger for synaptic vesicle (SV) fusion. VGCCs and the Ca microdomains they elicit must be located precisely to primed SVs, to evoke rapid transmitter release. Localization is mediated by Rab3 interacting molecule (RIM) and RIM-binding proteins (RIM-BPs), which interact and bind to the C-terminus of the CaV2 VGCC α-subunit. We studied this machinery at the mixed cholinergic/GABAergic neuromuscular junction (NMJ) of hermaphrodites. mutants had mild synaptic defects, through loosening the anchoring of UNC-2/CaV2 and delaying the onset of SV fusion. UNC-10/RIM deletion much more severely affected transmission. Even though postsynaptic depolarization was reduced, mutants had increased cholinergic (but reduced GABAergic) transmission, to compensate for the delayed release. This did not occur when the excitation-inhibition balance was altered by removing GABA transmission. Further analyses of GABA defective mutants and GABA or GABA receptor deletions, as well as cholinergic rescue of RIMB-1, emphasized that GABA neurons may be more affected than cholinergic neurons. Thus RIMB-1 function differentially affects excitation/inhibition balance in the different motor neurons, and RIMB-1 thus may differentially regulate transmission in mixed circuits. Untethering the UNC-2/CaV2 channel by removing its C-terminal PDZ ligand exacerbated the defects, and similar phenotypes resulted from acute degradation of the CaV2 β-subunit CCB-1. Therefore, untethering of the CaV2 complex is as severe as its elimination, yet does not abolish transmission, likely due to compensation by CaV1. Thus, robustness and flexibility of synaptic transmission emerges from VGCC regulation. The machinery for chemical synaptic transmission is organized in a precise spatial arrangement in order to enable efficient and temporally accurate coupling of action potentials with the rise of the Ca concentration through CaV2 P/Q-type voltage gated Ca channels. This triggers the fusion of synaptic vesicles with the plasma membrane and the release of transmitters. Here, we analyzed the molecular and functional interplay of proteins of the active zone scaffold, RIM and RIM-binding protein (RIMB-1), with the CaV2 channel in the neuromuscular junction, a tripartite synapse with cholinergic and GABAergic neuronal input. Our work shows a differential requirement of RIMB-1 in cholinergic vs. GABAergic neurons, that affects the regulation of excitation-inhibition balance at circuit, cellular and ultrastructural levels.
PubMed: 38951038
DOI: 10.1523/JNEUROSCI.0535-22.2024