Tissue Protein Research Articles

Chemoproteomics Sheds Light on Epigenetic Targets of [11C]Martinostat in the Human Brain.

Initiation of research programs to investigate binding specificity based on in vivo positron emission tomography (PET) imaging results can provide rich opportunities to improve data interpretation, gain biological insight, and inform hypothesis development. Here, we profile the binding specificity of the neuroepigenetic imaging probe, [11C]Martinostat. In vivo neuroimaging studies using [11C]Martinostat have uncovered differential regional uptake in relation to age and biological sex and in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and low-back pain compared to healthy controls. Previous studies using recombinant proteins and thermal shift assays in postmortem tissue indicate that [11C]Martinostat engages class I and putatively class IIb histone deacetylases (HDACs). While HDACs serve multiple functions, including regulation of chromatin remodeling and gene transcription, it is not known how differences in HDAC expression may arise across brain regions. HDACs functionally interact with a diverse array of multisubunit complexes, and engagement with associated binding partners may contribute to these differences. To further assess target engagement of [11C]Martinostat, we designed a synthetic probe based on the inhibitor structural scaffold for use in competition experiments followed by proteomic analysis in postmortem tissue. The synthetic probe, called Compound 4, appears to interact with the class I HDAC paralog HDAC2 and the class IIb paralog HDAC6 in a robust manner. We also uncovered unique interacting partners, including synaptic proteins from the synaptotagmin (SYT) family of proteins and neuronal pentraxin 2 (NPTX2). Further work to investigate HDAC associations with interacting proteins across regions of the human brain is needed to better understand neuroepigenetic dysregulation in psychiatric and neurological conditions.

Turning over new ideas in human skeletal muscle proteostasis: What do we know and where to from here?

Understanding the turnover of proteins in tissues gives information as to how external stimuli result in phenotypic change. Nowhere is such phenotypic change more conspicuous than skeletal muscle, which can be effectively remodelled by increased loading, ageing and unloading (disuse), all of which are subject to modification by nutrition and other environmental stimuli. The understanding of muscle proteome remodelling has undergone a renaissance recently with the reintroduction of deuterated water (D2O) and its ingestion to label amino acids and measure their incorporation into proteins. However, there is confusion around the use of the deuterated water methodology and the interpretation of the data it provides. Here, we provide a short review of some of the more salient features of the method and clarify some of the confusion around the method of deuterated water methods and its use in humans and how the interpretation of the data is in contrast to that of rodents.

Exploring the anti-inflammatory effects of phytochemicals in attenuating interstitial cystitis-a literature review

Interstitial cystitis is a fierce syndrome affecting the quality of life of thousands of individuals around the globe. It causes immense pain in the bladder and associated viscera along with inflammation-like lesions. The current medicinal and pharmacological research focuses on the protective and curative effects of phytochemicals in several ailments. Phytochemicals derived from many medicinal plants have shown potent outcomes in protection against various pathological conditions including interstitial cystitis. This review has summarized the insights of in vitro and in vivo studies regarding the effects of phytochemicals in fading the inflammation in bladder tissue and exhibiting a protective effect on the urothelium. Hemorrhagic cystitis is a common manifestation in patients undergoing chemotherapy with cyclophosphamide and related alkylating agents. Sodium 2-mercaptoethane sulfonate (Mesna) has traditionally been employed in clinical practice to counter cyclophosphamide-induced cystitis in humans. However, cyclophosphamide has been employed in developing animal models of interstitial cystitis in in vivo studies. Phytochemicals including quercetin, beta-caryophyllene, curcumol, boswellic acid, caftaric acid, some flavonoids and other secondary metabolites being a consequential component of numerous medicinal plants, have displayed a significant reduction in the levels of proinflammatory cytokines including TNF-α, NFĸB, IL-1β, NLRP3 inflammasome, IL-6, IL-2, matrix metalloproteinases etc. Uroprotective outcomes of these phytochemicals have been found to result in diminished oxidative stress and restoration of glutathione, superoxide dismutase, and related proteins in the inflamed bladder tissue. Many in vivo studies involving cyclophosphamide-induced interstitial cystitis have confirmed these findings. The coupling of phytotherapy with novel drug delivery systems such as nanoparticles, liposomes, nanotubes, quantum dots, etc. can help translate these beneficial effects of phytochemicals into clinical practice. Further investigations of these phytochemicals can provide intuition regarding the development of newer drug molecules having exclusive activity for attenuating interstitial cystitis.

Therapeutic effect of dihydroartemisinin on Alzheimer’s disease model mice with senile macular degeneration

ObjectivesThis study focuses on the preventive and therapeutic effects of Dihydroartemisinin (DHA) on Alzheimer’s disease (AD) model mice and the effects of DHA and donepezil on amyloid β-protein deposition and autophagy in nerve cells.MethodsSix autophagy related targets were selected for molecular docking with DHA to predict the affinity between DHA and the target. The AD mouse model was established and treated with donepezil and DHA, respectively. Morris water maze was used to detect the spatial learning and memory ability of AD mice. Hematoxylin eosin (he) staining was used to observe the structural changes of cerebral cortical neurons and retina, and transmission electron microscope was used to observe the structural changes of mitochondria and synapses. Immunohistochemistry (IHC) and immunofluorescence staining were used to detect the deposition of amyloid beta protein. Western blot was used to detect the expression of apoptosis and autophagy related proteins in the brain tissue of mice in each group.ResultsThe results of molecular docking showed that the selected active compounds had good binding activity with the target. The binding energy between DHA and Aβ, Bcl-2, ATG5, LC3, Caspase3, LAMP1 is −5.7, −7.0, −5.8, −7.2, −6.9 kcal/mol. The water maze test showed that compared with the wild type (WT) group, the spatial memory ability of AD model group mice (5× FAD) was significantly decreased, and the search time (27.62 ± 6.51 s vs. 282.80 ± 17.15 s) and average path (106.30 ± 29.65 cm vs. 993.20 ± 135.80 cm) were significantly prolonged. The application of donepezil and DHA significantly shortened the exploration time and average path (donepezil: 116.10 ± 10.58 s, 529.40 ± 106.00 cm; DHA: 99.71 ± 14.22 s, 373.30 ± 60.97 cm). The path to find the platform in DHA treatment group was shorter than donepezil treatment group (P < 0.05). HE staining showed that the arrangement of nerve cells in 5× FAD mice was disordered, and IHC showed that amyloid β-protein deposition was obvious. DHA and donepezil could improve the damage of cerebral cortex structure and reduce the deposition of extracellular amyloid β-protein in AD mice. Transmission electron microscopy showed that DHA and donepezil could reduce mitochondrial vacuolation and synaptic edema. The above results showed that DHA treatment effect was better than donepezil. Compared with the conventional feeding group, autophagy and apoptosis related proteins B-cell lymphoma-2 (BCL2) and anti-thymocyte globulin (ATG) were significantly down regulated in the 5× FAD group, and the expressions of BCL2 and ATG were increased after treatment with DHA and donepezil.ConclusionsDHA combined with BCL2 and ATG protein, through promoting autophagy protein, can reduce the damage of cerebral cortex structure in AD mice, reduce the deposition of extracellular β-amyloid protein, and then improve the memory ability of AD model mice. DHA treatment is superior to donepezil monotherapy.

Neuroprotective effect of Chenopodium pallidicaule flour (cañihuaco) suspension against ethanol toxicity in mice.

Introduction: Foods play an important role in the prevention of several neurodegenerative diseases. Chenopodium pallidicaule flour (cañihuaco) is characterized by its phytonutrients content, among them polyphenols which have the potential to exert neuroprotective properties. Objective: is to evaluate the effect of the administration of cañihuaco suspension against ethanol toxicity in mice Materials and methods: Experimental design. 35 male mice were used, receiving the following treatments, for five days: groups I-II water 10mL/kg, groups III-V received cañihuaco at doses of 200mg/kg, 400mg/kg and 800mg/kg respectively. On the fifth day, 99% ethanol was administered subcutaneously, 5g/kg, except for group I. After four hours mice were sacrificed by decapitation. The brain and cerebellum were extracted, weighted, and stored for histological analysis. Biochemical indicators were determined in the right hemisphere. Results: Group III and IV showed higher tissue protein levels (p&lt;0.05). Groups III-V showed higher levels of protein sulfhydryl groups being significant in group V (p&lt;0.01). There was no difference in GSH levels in any treatment group with respect to group II. At the histological level, group V showed preservation of nervous tissue. Conclusion: The administration of Chenopodium pallidicaule (cañihuaco) flour suspension at doses of 200, 400, and 800 mg/kg exhibits a dose-dependent reduction in histological damage in the brain and cerebellum. Additionally, it enhances the levels of protein SH groups.

IL-38 attenuates renal ischemia/reperfusion injury through suppressing inflammation in mice.

Inflammation plays an important role in the pathogenesis of renal ischemia/reperfusion injury (IRI). Interleukin-38 (IL-38) is an emerging cytokine with multiple functions involved in infection and immunity. The present study aimed to determine whether IL-38 attenuates renal IR injury in an animal model and to identify the underlying mechanisms. For this purpose, the renal IRI model was induced by left renal pedicle clamping for 45 min and right nephrectomy in mice. All mice were intraperitoneally injected with vehicle or IL-38. Renal histology, function, apoptosis and inflammatory cytokines were assessed. mRNAs were detected by Real-time PCR. The proteins were measured by Western blot. Results showed that the expression of IL-38 mRNA and protein in kidney tissue was significantly increased at 6 h and reached a peak at 24 h after renal IRI, along with the kidney dysfunction. IL-38 significantly decreased renal IRI, as reflected by the attenuation of renal dysfunction, tubular damage and cellular apoptosis. Thus, IL-38 markedly ameliorated the survival rate after renal IRI. In addition, IL-38 significantly increased the level of cytoplasmic IκB-α and suppressed the nuclear translocation of NF-κB, which inhibited the expression and release of inflammatory cytokines. In conclusion, IL-38 significantly protects against renal IRI probably by inhibiting pro-inflammatory reactions.

Identification of potential geosmin-binding proteins in grass carp gill based on affinity responsive target stability and tandem mass tag proteomics.

The escalating issue of water pollution, especially the accumulation of organic off-flavor pollutants, poses significant challenges. Geosmin, a typical off-flavor compound in aquatic environments, not only compromises the quality of aquatic products but also deters consumers. Its impact extends to aquatic organisms, with current research focusing on dose-response and ecotoxicity, while neglecting the molecular-level study of geosmin-binding proteins. This study employs an integrated approach combing affinity-responsive target stability in vitro, tandem mass tag proteomics in vivo, and molecular docking to identify geosmin-binding proteins in the gill tissue of grass carp (Ctenopharyngodon idella). ARTS analysis identified 56 proteins, predominantly membrane-associated proteins, such as catenin beta-1, annexin, and integrin beta. Proteomic analysis revealed 256 differentially expressed proteins in geosmin-exposure group, with 18 common proteins screened by in vivo and in vitro methods. Among these, annexin, cathepsin D, and interleukin-1 receptors were highlighted as potential geosmin targets, with annexin demonstrating the highest binding affinity in silico. This study provides a robust protocol integrating in vivo, in vitro, and in silico approaches to elucidate geosmin's target proteins in grass carp gill tissue, advancing our understanding of pollutant-biological interactions and enhancing environmental risk assessment accuracy.

EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with poorly understood underlying molecular mechanisms. Ferroptosis, a form of programmed cell death, is not fully elucidated in NPC. We conducted quantitative proteomics to detect dysregulated proteins in NPC tissues. The levels of endoplasmic reticulum membrane protein complex 2 (EMC2) in NPC tissue microarrays were evaluated by immunohistochemistry, and the prognostic value of EMC2 was analyzed in NPC patients. The role of EMC2 in ferroptosis and carcinogenesis was determined through in vitro and in vivo experiments. Quantitative proteomics, protease inhibition, ubiquitin detection, and rescue experiments were performed to explore the mechanism of EMC2-regulated ferroptosis. Significantly upregulated EMC2 was detected in NPC, and it was closely related to the characteristics of tumor progression. Elevated EMC2 was obviously correlated with poor survival in patients with NPC. EMC2 knockdown promoted ferroptosis, inhibiting cell viability, migration, and invasion, and enhancing the efficacy of cisplatin in NPC cells. Conversely, EMC2 overexpression contributed to ferroptosis repression, malignant progression, and reduced the efficacy of cisplatin. In addition, EMC2 knockdown suppressed xenograft tumor growth and enhanced ferroptosis in nude mice. Mechanistically, we identified transferrin receptor (TFRC) as a critical downstream protein. EMC2 interacted with TFRC and promoted its ubiquitin-proteasomal degradation. EMC2 regulated ferroptosis by mediating the level of TFRC. EMC2 suppresses ferroptosis and promotes tumor progression, and the EMC2-TFRC axis is a novel ferroptosis regulatory pathway. EMC2 is a potentially biomarker and therapeutic target for NPC.

Dahuang-Gancao decoction ameliorates testosterone-induced androgenetic alopecia in mice.

Dahuang-Gancao decoction (DGD) is a traditional Chinese medicinal formula that is recorded in the Synopsis of the Golden Chamber, and is widely used to treat damp-heat in the body. Since the pathological factors of androgenetic alopecia (AGA) also reflect damp-heat blockage, DGD has great potential for the treatment of AGA and has been used effectively in clinical practice. The aim of the study was to investigate whether external application of DGD could promote the activation and proliferation of hair follicle stem cells (HFSCs) and improve AGA through the Wnt/β-catenin pathway. The main chemical components of DGD-contained serum were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and database search. Cell Counting Kit-8 (CCK8) was used to investigate the appropriate concentration. Hair regeneration was assessed by hair growth score and histopathological staining. The proliferation of HFSCs and the activation of Wnt/β-catenin pathway were detected by Western blot, immunofluorescence staining, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The AGA mouse model was induced by external application of testosterone (T). Immunofluorescence staining was performed to localize HFSCs by CK15, followed by staining with Ki67, β-catenin, and Cyclin D1, respectively. The results illustrated that the 10% DGD group and the 10% DGD+HLY78 group could significantly promote the expression of Wnt10b and β-catenin and the proliferation of HFSCs in vitro, while the 10% DGD+IWR-1 group could reverse the promotion effect of DGD. Animal experiments showed that compared with the model group (T group), DGD promoted hair follicles to enter the anagen phase, as evidenced by an increase in hair growth score, an increase in the number of hair follicles in hematoxylin and eosin (HE) staining, and a significant increase in the ratio of the number of anagen follicles to the total number of hair follicles (AF/AF+TF). In addition, DGD upregulated the expression of Wnt/β-catenin signaling pathway proteins in the skin tissues of AGA mice. It also promoted the proliferation of HFSCs and the expression of β-catenin and Cyclin D1 cytokines in the region of HFSCs. Both oral and external application of DGD can promote the proliferation of HFSCs by activating the Wnt/β-catenin signalling pathway. External application of DGD can promote the hair follicles to enter the anagen phase, which can ameliorate the symptoms of alopecia in AGA mice. Therefore, compared to oral DGD, external application of DGD is an effective and safer way of administration for the treatment of AGA.

Gastroprotective effect of fucoidan from Sargassum siliquastrum against ethanol-induced gastric mucosal injury.

The ethanol-induced BALB/c mice and human gastric epithelial cell (Ges-1 cell) models were used to investigate the Sargassum siliquastrum fucoidan (SFuc) gastroprotective capability. The injury score and histopathological sections of the stomach were used to evaluate the gastroprotective capability. The western blotting and RT-PCR methods determined the signaling mechanism of mice's gastric injury. SFuc is fucoidan with a molecular weight of 300.7 and 25.1kDa. The injury score and ulcer index of the SFuc-200 group decreased by 3.85 and 2.06 folds in contrast with the Model group, respectively. The findings indicated that SFuc reduced oxidative stress and inflammatory factor expression in the gastric mucosa by downregulating the levels of associated genes within the TLR-4, MyD88, and MAPK/NF-κB signaling pathways. Meanwhile, the SFuc-200 group promoted the expressions of EGF and PGE 2 by 1.53 and 1.52 folds, respectively. Together with the expression inhibition of p38, ERK, JNK, and NF-κB proteins in gastric tissue to help for differentiation of gastric cells. In addition, SFuc significantly reduced apoptosis occurrence in mice and Ges-1 cells. Our study provides potential mechanism clues of the SFuc's resistance to ethanol-induced gastric mucosal damage, suggesting its potential functional food for gastric protection.

Achieving theranostic probes targeting BRD3/BRD4 for imaging and therapy of tumor.

The BET family proteins play pleiotropic roles in the tumorigenesis and growth of various human malignancies that have aroused great interests as the cancer therapeutic targets. Therefore, it's significant to develop labeling toolkits for the dynamic monitoring of BET family proteins in living tumor cells and tissue slices. In particular, there are few small-molecule fluorescent probes based on BET family proteins developed for real-time imaging of these proteins in tumor cells and tissues and treatment of breast cancer. In general, antibodies of BET family proteins are chosen for imaging of these proteins. However, the cost of these antibodies is more expensive than small molecules and the operation is relatively complicated. Moreover, the antibodies for imaging are not capable of the therapy for breast cancer. Thus, it's essential to exploit a novel imaging system for BET family proteins which is easy-operating and economical, with achieving therapeutic effects simultaneously. Therefore, a series of fluorescent probes (17-21) targeting BET family proteins were developed. Through the evaluation studies, probe 17 showed advantages in docking studies, analysis of cell viability, and imaging studies. Importantly, probe 17 was capable of distinguishing tumor cells and tissue slices and made a distinction between them by labeling BRD3 and BRD4 proteins. Importantly, probe 17 showed higher resolution in mouse tumor and human tumor slice imaging than BRD3 and BRD4 antibodies. Moreover, compared with these antibodies, probe 17 was more stable, more economical and easier to operate in the imaging assays. In addition, it also played an anti-tumor role by inducing cell apoptosis, proliferation inhibition, and cycle arrest in tumor cells. All these features render probe 17 to perform as an effective labeling toolkit compatible for imaging studies of BRD3/BRD4, as well as an approach to diagnosis and treatment of breast cancer.

LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid.

Lysophosphatidylcholine acyltransferase 3 (LPCAT3) promotes ferroptosis through the incorporating polyunsaturated fatty acids into membrane phospholipids, however, its role in serous ovarian cancer remains unclear. Here explored cancer proliferation and metastasis after modulating LPCAP3. LPCAT3 protein in ovarian cancer tissues was detected using bioinformatic and immunohistoche mical assays. Cell behaviors were observed after up- or down-regulating LPCAT3. Lipid metabolites were determined, and then the pathway enrichment analysis was performed. The expression level of LPCAT3 in serous ovarian cancer tissues was lower than that in other types of ovarian cancer, and high expression was associated with a longer survival time. Overexpressing LPCAT3 reduced cell proliferation, migration and invasion via enhancing ferroptosis and decreasing the survival signaling; these behaviors were enhanced in LPCAT3-downknocked cells, where a higher abundance of arachidonic acid was observed followed by up-regulation of the downstream survival signaling. In vivo, up-regulation of LPCAT3 decreased tumor growth, but down-regulation enhanced tumor growth and metastasis. LPCAT3 modulated metabolism of arachidonic acid, thereby regulating ferroptosis and the survival signaling to determine cancer growth and metastasis.

Eliminating the persistent HIV reservoir based on biomarker expression - How do we get there?

Persistent HIV reservoir with different levels of proviral transcriptional activity represents a hurdle to HIV cure. The absence of a specific molecular signature or a "biomarker" to define cells latently infected with HIV limits reservoir eradication efforts. Biomarkers proposed in the literature define subsets of latently infected cells. This article discusses factors contributing to biomarker heterogeneity: external stimuli the cells are exposed to, tissue microenvironments, and person-to-person variation. Despite reservoir heterogeneity, several biomarkers, e.g., programmed cell death 1 and the Fc fragment of IgG low affinity IIa receptor, were reported consistently in multiple studies; however, they alone are unlikely to define all the HIV reservoir cells. Identifying a minimal set of cell surface proteins that together define all reservoir subsets is needed. Future studies will need to focus on the identification of co-expressed proteins that define the same sets of cells to reduce the number of proteins in a biomarker panel. A detailed characterization of tissue biomarkers and proteins expressed in latently infected cells of the myeloid lineage is needed to ensure that all the reservoirs are targeted throughout the body. Furthermore, the effect of underlying conditions that develop as people with HIV age on the manifestation of latency should be evaluated. With the development of novel technologies, such as spatial transcriptomics and proteomics, such endeavors will soon be possible. Thus, there is promise that a minimal set of proteins defining all the different reservoir subsets can be identified and developed into a reservoir targeting strategy.

Differential Expression of Hard Tissue Proteins in Hypomineralized Second Primary Molars in Comparison to Normal Teeth.

This study aims to identify the proteins in hypomineralized second primary molars (HSPMs) and correlate their function in Amelogenesis. HSPM is a qualitative defect of the enamel of the second primary molars with no clear etiology. Total protein quantification was performed using the Bradford Protein Assay, followed by the electrophoretic separation of samples using 2D-Gel electrophoresis to identify the proteins. The results from the Bradford Protein Assay unveiled a five-fold increase in the protein content in HSPM. Proteins such as Dentin sialo-phosphoprotein (DSPP), Keratin, type I, Serum Albumin, Anti-thrombin III, Alpha-1-Antitrypsin, Histone H3.2, Actin, Heat shock Protein, Vimentin, Desmoglein-3, Glyceraldehyde-3-phosphate dehydrogenase, Inosine-5'-monophosphate dehydrogenase 2, Zinc Alpha 2 glycoprotein, Lysozyme C, Prothrombin, Vit-D binding Protein, Apolipoprotein A-1, Defensin 1, Immunoglobulin Gamma, Immunoglobulin Kappa, and Alpha-Amylase were all upregulated (p < 0.05) in HSPM. This investigation conclusively demonstrates that HSPM-affected teeth have higher protein content than healthy teeth. The study also supports the theory of proteolytic inhibition attributed to reduced protease activity and heightened protease inhibitor activity.

Inhibition of id-1 reduces osteosarcoma growth and metastasis through mediation of snail

ObjectiveOsteosarcoma (OS) is a highly invasive bone tumor that frequently metastasizes to the lungs. This study aims to investigate the role of the Id-1 gene in OS invasion and metastasis, and its relationship with the Snail gene.MethodsThis study included tissue samples from 12 non-metastatic osteosarcomas and 9 metastatic osteosarcoma patients to examine the expression of Id-1 and Snail using RT-qPCR and analyze their correlation. In cell-based experiments, four osteosarcoma cell lines (Saos-2, U2OS, MG-63, and 143B) and the human osteoblast cell line hFOB 1.19 were cultured. The expression of Id-1 and Snail was evaluated by RT-qPCR and Western blotting.Cells were randomly divided into the Control group, sh-NC group, and sh-Id-1 group using lentiviral infection. Transwell invasion and scratch assays were used to assess cell migration and invasion. WB was employed to detect the expression of Id-1, Snail, and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, vimentin, and N-cadherin) in the OS cells of each group. In animal experiments, Tumor formation in each group was evaluated by injecting cells subcutaneously into mice. An osteosarcoma lung metastasis model was established by injecting infected cells into the tibia of mice. Tumor growth and lung metastasis were observed using HE staining. The expression of Id-1, Snail, and EMT-related proteins in osteosarcoma and lung tissues from each group of mice was assessed using Western blot and immunohistochemistry.ResultsThe expression of Id-1 and Snail was significantly higher in osteosarcoma tissues than in normal bone tissues, and the expression of Id-1 was positively correlated with that of Snail. In cell experiments, downregulation of Id-1 reduced Snail expression and significantly inhibited EMT, as well as the migration and invasion of OS cells (P < 0.05). In animal experiments, compared to the Control group, the sh-Id-1 group mice was no significant change in body weight, but the tumor volume was significantly reduced, and fewer lung metastatic nodules (P < 0.05). HE staining indicated decreased nuclear atypia, reduced invasion and destruction, fewer new blood vessels, and less calcification in the sh-Id-1 group tumors. Immunohistochemistry and WB results showed upregulation of E-cadherin and downregulation of vimentin, N-cadherin, Id-1, and Snail in the sh-Id-1 group (P < 0.05).ConclusionDownregulation of Id-1 inhibits the EMT process by reducing Snail expression, effectively suppressing the growth, invasion, and lung metastasis of OS.

High temperature induces oxidative damage, immune modulation, and atrophy in the gills and skeletal muscle of the teleost fish black cusk-eel (Genypterus maculatus).

The high temperature associated with heat waves is a relevant abiotic factor that could impact the biology of teleost fish. The innate immune response, muscular growth, and oxidative stress status are relevant functions in fish tissues that could be affected by increased temperature. In this study, black cusk-eel (Genypterus maculatus) juveniles were subjected to increased temperature, to experimentally replicate heat waves registered from the South Pacific Ocean for five days. The results showed that thermal stress modulated the immune response in gills, with up-regulation of antibacterial peptides, pro-inflammatory cytokines, and Toll-like receptors genes, including hepcidin, gzma, tnfa, cxcl8, and tlr5, with no effect on complement system genes. In skeletal muscle, high temperature triggered atrophy-related gene expression, with up-regulation of foxo1, foxo3, fbxo32, murf1, and atg16l. Increased temperature also generated an up-regulation of transcripts encoding heat shock protein (hsp60 and hsp70) in gills and skeletal muscle, generating oxidative stress in both tissues, with increased expression of the antioxidant genes sod1 and gpx1 in gills and skeletal muscle, respectively, with oxidative damage observed at the DNA level (AP sites), protein (carbonyl content), and lipoperoxidation (HNE content) in both tissues. The present study shows that short-term increases in temperature like those observed in heat waves could affect the immune response in gills, induced atrophy in skeletal muscle, and generate oxidative stress in a teleost species important for Chilean aquaculture diversification, information relevant under the context of climate change scenario.

High-Density Lipoproteins from Coronary Artery Disease and Aortic Valve Stenosis Patients Differentially Regulate Gene Expression in a Model of Cardiac Adipocytes

Previous reports have described a statistical association between high-density lipoproteins (HDL) subclasses and the expression of genes coding for pro-calcifying proteins in the epicardial adipose tissue of patients with coronary artery disease (CAD) and aortic valvular stenosis (AVS). These results suggest a causal relationship between HDL and the regulation of gene expression in epicardial adipose tissue. However, there is no experimental evidence that supports this causal relationship. Therefore, we explored the effect of HDL isolated from CAD or AVS patients on the expression of OPN, BMP2, and BMP4, genes coding for proteins related to calcification, osteopontin, and bone morphogenetic proteins -2 and -4, respectively, and LEP, UCP, and PER, coding for leptin, uncoupling protein-1, and perilipin-2, respectively, proteins that confer phenotypic characteristics to adipocytes. The experiments were performed using a novel model of cardiac adipocytes differentiated in vitro from stromal cells of rabbit cardiac adipose tissue. AVS or CAD patients’ HDL differentially modulated the expression of BMP4 and LEP, whereas HDL from both kinds of patients upregulated the OPN gene expression. A high concentration of triglycerides associated to small HDL and a higher concentration of phospholipids of large HDL from CAD patients than those from AVS individuals were the most remarkable structural differences. Finally, we demonstrated that cholesterol from reconstituted HDL was internalized to the adipocytes. The regulation of genes related to the secretory activity of cardiac adipocytes mediated by HDL has clinical implications as a potential therapeutic target for the prevention and treatment of CAD and AVS. In summary, the HDL isolated from the CAD and AVS patients differentially regulated gene expression in adipocytes by a mechanism that seems to be dependent on HDL lipid internalization to the cells and structural characteristics of the lipoproteins.

Utility of left atrial strain in differentiating between cardiac amyloidosis and hypertrophic cardiomyopathy

Abstract Introduction and Objectives Cardiac amyloidosis (AL) is a disease characterized by the abnormal accumulation of anomalous proteins in cardiac tissue, while hypertrophic cardiomyopathy (HCM) is a hereditary cardiac disease characterized by abnormal thickening of the cardiac muscle, associated with tissue fibrosis and cardiac dysfunction in its natural progression. The echocardiogram has emerged as a fundamental tool in the diagnosis and follow-up of these patients, and strain analysis techniques can provide highly useful additional information on cardiac function in these patients, especially in the early stages of the disease. We questioned whether it might be useful in differentiating between these two diseases. Methods This retrospective analysis included adult patients who had undergone echocardiography at our center during the years 2023-2024. A total of 52 patients with a confirmed diagnosis of transthyretin AL confirmed by scintigraphy and/or biopsy, and another group of 51 patients with a confirmed diagnosis of HCM and ICD carriers for being high-risk patients were included. Various left atrial strain values (Reservoir, Conduit, and Pump) were analyzed. Descriptive statistics were calculated for each group and segment, and the Mann-Whitney U test was used to compare the groups. Results Patients with AL showed significantly lower absolute strain values compared to patients with HCM in all three analyzed varieties (Reservoir, Conduit, and Pump) with p&amp;lt;0.01 for all comparisons. The mean strain in the HCM group was 18.57 for reservoir strain, -11.85 for conduit strain, and -6.94 for pump strain; while the mean in the AL group was 9.28, -6.93, and -3.10, respectively. Conclusions Our study found significant differences in left atrial strain values between patients with HCM and patients with transthyretin AL. These findings suggest that left atrial strain analysis could be useful in evaluating cardiac function, follow-up, and differential diagnosis between patients with AL and HCM, especially in the earlier stages of the disease, where it is more challenging to establish a reliable diagnosis. HCM Vs amyloidosis

Utility of left atrial strain in differentiating between cardiac amyloidosis and reablated atrial fibrillation

Abstract Introduction and Objectives Cardiac amyloidosis (AL) is a disease characterized by the abnormal accumulation of anomalous proteins in cardiac tissue, while atrial fibrillation (AF) is an exceedingly prevalent arrhythmia in the current population, often related to the amount of atrial fibrosis. The echocardiogram has emerged as a fundamental tool in the diagnosis and follow-up of these patients, and strain analysis techniques can provide highly useful additional information on cardiac function in these patients, especially in the early stages of the disease. We questioned whether it might be useful in differentiating between these two pathologies. Methods This retrospective analysis included adult patients who had undergone echocardiography at our center during the years 2023-2024. A total of 52 patients with a confirmed diagnosis of AL by transthyretin, confirmed by scintigraphy and/or biopsy, and another group of 47 patients with recurrent AF with at least two ablation procedures were included. Various left atrial strain values (Reservoir, Conduit, and Pump) were analyzed. Descriptive statistics were calculated for each group and segment, and the Mann-Whitney U test was used to compare the groups. Results Patients with AL showed significantly lower absolute strain values compared to patients with reablated AF in all three analyzed varieties (Reservoir, Conduit, and Pump) with p&amp;lt;0.01 for all comparisons. The mean strain in the reablated AF group was 17.42 for reservoir strain, -11.72 for conduit strain, and -6.33 for pump strain; while the mean in the AL group was 9.28, -6.93, and -3.10, respectively. Conclusions Our study found significant differences in left atrial strain values between patients with reablated AF and patients with transthyretin AL. These findings suggest that left atrial strain analysis could be useful in evaluating cardiac function, follow-up, and differential diagnosis between patients with AL and reablated AF, especially in the earlier stages of the disease, where it is more challenging to establish a reliable diagnosis. Atrial fibrillation Vs amyloidosis

In Vitro and In Vivo Anticancer Activities of Water-Soluble Ru(II)(η6-p-cymene) Complexes via Activating Apoptosis Central Regulators and Possibilities of New Antitumor Strategies in Triple Negative Breast Cancers.

In this study, we synthesized 12 monofunctional tridentate ONS-donor salicylaldimine ligand (L)-based Ru(II) complexes with general formula [(Ru(L)(p-cymene)]+·Cl- (C1-C12), characterized by 1H NMR, 13C NMR, UV, FT-IR spectroscopy, HR-ESI mass spectrometry, and single-crystal X-ray analysis showing ligand's orientation around the Ru(II) center. All 12 of these 12 complexes were tested for their anticancer activities in multiple cancer cells. The superior antitumor efficacy of C2, C8, and C11 was demonstrated by reduced mitochondrial membrane potential, impaired proliferative capacity, and disrupted redox homeostasis, along with enhanced apoptosis through caspase-3 activation and downregulation of Bcl-2 expression. In the 4T1 breast cancer orthotopic mouse model, assessment of bioluminescence for metastatic spread, tumor burden, histopathological evaluation, immunohistochemistry (IHC), and hematological profiling and tissue Protein expression of caspase-3, cleaved caspase-3, TNF-α, and bcl-2 demonstrated that C8 treatment led to prolonged survival and suppressed tumor progression in triple negative breast cancer.