Related Cellular Processes Research Articles

Synergistic Inhibitory Effects of Tetramethylpyrazine and Evodiamine on Endometriosis Development.

Endometriosis (EMS) belongs to a gynecological disorder with inflammation and the existence of endometrial-like tissues beyond the uterus, often leading to infertility and pelvic pain. Estrogen receptor β (ERβ) is significantly expressed in endometriosis (EMS) and recognized as a promising therapeutic target for EMS treatment by inhibiting ERβ activity. In this study, we investigated the potential mechanisms for tetramethylpyrazine (TMP)-mediated ERβ suppression, and the synergistic inhibitory effect of TMP and evodiamine (EVO) on ERβ expression and EMS development. We found that TMP suppresses ERβ expression by reducing the association of Oct3/4 with the ERβ promoter and decreasing Oct3/4 protein levels without affecting Oct3/4 transcript levels. A minimum dosage of 10µM TMP is required to inhibit ERβ expression. Neither TMP (5µM) nor EVO (2µM) alone had any effect, but their combination synergistically inhibited ERβ expression and modulated related cellular processes, including redox balance, mitochondrial function, inflammation, and proliferation. Additionally, the combination of TMP (10mg/kg body weight) and EVO (5mg/kg) synergistically inhibited ERβ expression and EMS development in the mouse model. In conclusion, TMP suppresses ERβ expression by reducing the association of Oct3/4 with the ERβ promoter. Neither TMP nor EVO alone effectively suppresses ERβ in both laboratory and live organism models. However, their combination synergistically inhibits ERβ expression and EMS development, suggesting a potential therapeutic strategy for EMS using TMP and EVO.

Assessing sarcoma cell cytoskeleton remodeling in response to varying collagen concentration

Sarcomas, rare malignant tumors of mesenchymal origin, are often underdiagnosed and have face diagnostic ambiguities and limited treatment options. The main objective of this study was to define the nanomechanical and biophysical properties of sarcoma cells, particularly examining how the cytoskeleton's remodeling and related cellular processes such as cell migration and invasion in response to environmental stimuli due to collagen content. Utilizing one murine fibrosarcoma and one osteosarcoma cell line we employed atomic force microscopy, immunostaining, advanced image processing, in vitro cellular assays, and molecular techniques to investigate cells' cytoskeleton remodeling in response to varying collagen concentration. Our study focused on how alterations in collagen content affects the cytoskeletal dynamics and correlate with changes in gene expression profiles relevant to metastasis and an aggressive cancer phenotypes. Our findings indicate that despite their shared classification, fibrosarcoma and osteosarcoma cells display distinct biophysical properties and respond differently to mechanical forces. Notably, this difference in cellular behavior renders mechanical properties a potent novel biomarkers. Furthermore, the metastasis-related identified genes related to metastatic capability, could be potential therapeutic targets. This study highlights the significance of understanding the unique traits of sarcoma cells to improve diagnostic precision and expand therapeutic strategies, for this rare type of cancer.

The Integration of Gold Nanoparticles into Dental Biomaterials as a Novel Approach for Clinical Advancement: A Narrative Review.

Gold nanoparticles (AuNPs) have gained significant attention in the biomedical field owing to their versatile properties. AuNPs can be customized by modifying their size, shape and surface characteristics. In recent years, extensive research has explored the integration of AuNPs into various dental materials, including titanium, polymethylmethacrylate (PMMA) and resin composites. This review aims to summarize the advancements in the application of modified AuNPs in dental materials and to assess their effects on related cellular processes in the dental field. Relevant articles published in English on AuNPs in association with dental materials were identified through a systematic search of the PubMed/MEDLINE, Embase, Scopus and ScienceDirect databases from January 2014 to April 2024. Future prospects for the utilization of AuNPs in the field of dentistry are surveyed.

Using microRNAs Networks to Understand Pancreatic Cancer-A Literature Review.

Pancreatic cancer is a severe disease, challenging to diagnose and treat, and thereby characterized by a poor prognosis and a high mortality rate. Pancreatic ductal adenocarcinoma (PDAC) represents approximately 90% of pancreatic cancer cases, while other cases include neuroendocrine carcinoma. Despite the growing knowledge of the pathophysiology of this cancer, the mortality rate caused by it has not been effectively reduced. Recently, microRNAs have aroused great interest among scientists and clinicians, as they are negative regulators of gene expression, which participate in many processes, including those related to the development of pancreatic cancer. The aim of this review is to show how microRNAs (miRNAs) affect key signaling pathways and related cellular processes in pancreatic cancer development, progression, diagnosis and treatment. We included the results of in vitro studies, animal model of pancreatic cancer and those performed on blood, saliva and tumor tissue isolated from patients suffering from PDAC. Our investigation identified numerous dysregulated miRNAs involved in KRAS, JAK/STAT, PI3/AKT, Wnt/β-catenin and TGF-β signaling pathways participating in cell cycle control, proliferation, differentiation, apoptosis and metastasis. Moreover, some miRNAs (miRNA-23a, miRNA-24, miRNA-29c, miRNA-216a) seem to be engaged in a crosstalk between signaling pathways. Evidence concerning the utility of microRNAs in the diagnosis and therapy of this cancer is poor. Therefore, despite growing knowledge of the involvement of miRNAs in several processes associated with pancreatic cancer, we are beginning to recognize and understand their role and usefulness in clinical practice.

Network pharmacology, molecular docking, and dynamics analyses to predict the antiviral activity of ginger constituents against coronavirus infection.

COVID-19 is a global pandemic that caused a dramatic loss of human life worldwide, leading to accelerated research for antiviral drug discovery. Herbal medicine is one of the most commonly used alternative medicine for the prevention and treatment of many conditions including respiratory system diseases. In this study, a computational pipeline was employed, including network pharmacology, molecular docking simulations, and molecular dynamics simulations, to analyze the common phytochemicals of ginger rhizomes and identify candidate constituents as viral inhibitors. Furthermore, experimental assays were performed to analyze the volatile and non-volatile compounds of ginger and to assess the antiviral activity of ginger oil and hydroalcoholic extract. Network pharmacology analysis showed that ginger compounds target human genes that are involved in related cellular processes to the viral infection. Docking analysis highlighted five pungent compounds and zingiberenol as potential inhibitors for the main protease (Mpro), spike receptor-binding domain (RBD), and human angiotensin-converting enzyme 2 (ACE2). Then, (6)-gingerdiacetate was selected for molecular dynamics (MD) simulations as it exhibited the best binding interactions and free energies over the three target proteins. Trajectories analysis of the three complexes showed that RBD and ACE2 complexes with the ligand preserved similar patterns of root mean square deviation (RMSD) and radius of gyration (Rg) values to their respective native structures. Finally, experimental validation of the ginger hydroalcoholic extract confirmed the existence of (6)-gingerdiacetate and revealed the strong antiviral activity of the hydroalcoholic extract with IC of 2.727 . Our study provides insights into the potential antiviral activity of (6)-gingerdiacetate that may enhance the host immune response and block RBD binding to ACE2, thereby, inhibiting SARS-CoV-2 infection.

The role of non-coding RNAs in muscle aging: regulatory mechanisms and therapeutic potential.

Muscle aging is a complex physiological process that leads to the progressive decline in muscle mass and function, contributing to debilitating conditions in the elderly such as sarcopenia. In recent years, non-coding RNAs (ncRNAs) have been increasingly recognized as major regulators of muscle aging and related cellular processes. Here, we comprehensively review the emerging role of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in the regulation of muscle aging. We also discuss how targeting these ncRNAs can be explored for the development of novel interventions to combat age-related muscle decline. The insights provided in this review offer a promising avenue for future research and therapeutic strategies aimed at improving muscle health during aging.

Cytotoxicity of dioncophylline A and related naphthylisoquinolines in leukemia cells, mediated by NF-κB inhibition, angiogenesis suppression, G2/M cell cycle arrest, and autophagy induction

BackgroundInhibition of NF-κB activity represents a strategy to treat acute myeloid leukemia, one of the most lethal leukemia types. Naphthylisoquinolines (NIQs) are cytotoxic alkaloids from lianas of the families Ancistrocladaceae and Dioncophyllaceae, which are indigenous to tropical rainforests. PurposeUncovering therapeutic possibilities and underlying molecular mechanisms of dioncophylline A and its derivatives towards NF-κB related cellular processes. MethodsResazurin-based cell viability assay was performed for dioncophylline A and three derivatives on wild-type CCRF-CEM and multidrug-resistant CEM/ADR5000 cells. Transcriptome analysis was executed to discover cellular functions and molecular networks associated with dioncophylline A treatment. Expression changes obtained by mRNA microarray hybridization were confirmed using qRT-PCR. Molecular docking was applied to predict the affinity of the NIQs with NF-κB. To validate the in silico approach, NF-κB reporter assays were conducted on HEK-Blue™ Null1 cells. Cell death mechanisms and cell cycle arrest were studied using flow cytometry. The potential activity on angiogenesis was evaluated with the endothelial cell tube formation assay on HUVECs using fluorescence microscopy. Intracellular NF-κB location in HEK-Blue™ Null1 cells was visualized with immunofluorescence. Finally, the anti-tumor activity of dioncophylline A was studied by a xenograft zebrafish model in vivo. ResultsOur study demonstrated that dioncophylline A and its derivatives exerted potent cytotoxicity on leukemia cells. Using Ingenuity Pathway Analysis, we identified the NF-κB network as the top network, and docking experiments predicted dioncophylline A and two of its derivatives sharing the same binding pocket with the positive control compound, triptolide. Dioncophylline A showed the best inhibitory activity in NF-κB reporter assays compared to its derivatives, caused autophagy rather than apoptosis, and induced G2/M arrest. It also prevented NF-κB translocation from the cytoplasm to the nucleus. Tube formation as an angiogenesis marker was significantly suppressed by dioncophylline A treatment. Finally, the remarkable anti-tumor activity of dioncophylline A was proven in zebrafish in vivo. ConclusionTaken together, we report for the first time the molecular mechanism behind the cytotoxic effect of dioncophylline A on leukemia cells. Dioncophylline A showed strong cytotoxic activity, inhibited NF-κB translocation, significantly affected the NF-κB in silico and in vitro, subdued tube formation, induced autophagy, and exerted antitumor activity in vivo. Our findings enlighten both the cellular functions including the NF-κB signaling pathway and the cytotoxic mechanism affected by dioncophylline A.

Deacetylation of ATG7 drives the induction of macroautophagy and LC3-associated microautophagy

ABSTRACT LC3 lipidation plays an important role in the regulation of macroautophagy and LC3-associated microautophagy. The E1-like enzyme ATG7 is one of the core components that are directly involved in LC3 lipidation reaction. Here, we provide evidence showing that acetylation of ATG7 tightly controls its enzyme activity to regulate the induction of macroautophagy and LC3-associated microautophagy. Mechanistically, acetylation of ATG7 disrupts its interaction with the E2-like enzyme ATG3, leading to an inhibition of LC3 lipidation in vitro and in vivo. Functionally, in response to various different stimuli, cellular ATG7 undergoes deacetylation to induce macroautophagy and LC3-associated microautophagy, which are necessary for cells to eliminate cytoplasmic DNA and degrade lysosome membrane proteins, respectively. Taken together, these findings reveal that ATG7 acetylation acts as a critical rheostat in controlling LC3 lipidation and related cellular processes. Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy-related; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; CREBBP/CBP: CREB binding protein; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EP300/p300: E1A binding protein p300; IFNB1: interferon beta 1; ISD: interferon stimulatory DNA; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEF: mouse embryonic fibroblast; MTOR: mechanistic target of rapamycin kinase; NAM: nicotinamide; PE: phosphatidylethanolamine; PTM: post-translational modification; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SIRT: sirtuin; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TSA: trichostatin A; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2; WT: wild-type.

Modulating Effects of Vitamin K2 on Oxidative Stress Induced Organelle Damage in Alzheimer’s Disease

AbstractBackgroundCurrent treatment strategies for AD are either involved in an improved amyloid‐beta precursor protein (APP) processing via inhibition and/or activation of enzymatic machinery. Whereas, others drug regimen includes the use of putative tau kinase inhibitors, microtubule stabilizers and tau immunotherapies. Moreover, therapies to combat oxidative stress are currently being devised because oxidative stress plays a major role innneurodegeneration. Interestingly, current studies are being focused on the screening of bioactive compounds for their effect on prevention of Aβ formation, oxidative stress reduction and targeting organelle dysfunction, which will potentiate the use of bioactive compounds to prevent AD in early stages. Vitamin K2 is one of the bioactive compounds which has gained importance for its role as an antioxidant.MethodTo understand the neuroprotective effect of vitamin K2 during metabolic complications, SH‐SY5Y cells were treated with streptozotocin for 24 h and menadione for 2 h in a dose dependent manner, followed by the post treatment of vitamin K2 for 5 h. Modulating effects of vitamin K2 on cell viability, Lactate Dehydrogenase release, reactive oxygen species (ROS), mitochondrial membrane potential, ER stress marker (CHOP), an indicator of unfolded protein response (UPR) p‐IRE1α, GSK 3α/β, total tau and Aβ 42 were studied.ResultVitamin K2 significantly reduced the neuronal cell death by inhibiting the cytotoxicity, ROS levels and helped in the retainment of mitochondrial membrane potential. Moreover, vitamin K2 significantly decreased the expression of CHOP protein along with the levels and the nuclear localization of p‐IRE1 α, thus showing its significant role in inhibiting chronic ER stress mediated UPR and eventually apoptosis. In addition, Vitamin K2 significantly downregulated the expression of GSK 3 α/β together with the levels of total tau protein, with petite effect on secreted Aβ 42 levels.ConclusionVitamin K2 ameliorated mitochondrial damage, ER stress and tauopathy mediated neuronal cell death, highlighting its role as a novel antioxidative therapeutics targeting related cellular processes.

Giant cells: multiple cells unite to survive.

Multinucleated Giant Cells (MGCs) are specialized cells that develop from the fusion of multiple cells, and their presence is commonly observed in human cells during various infections. However, MGC formation is not restricted to infections alone but can also occur through different mechanisms, such as endoreplication and abortive cell cycle. These processes lead to the formation of polyploid cells, eventually resulting in the formation of MGCs. In Entamoeba, a protozoan parasite that causes amoebic dysentery and liver abscesses in humans, the formation of MGCs is a unique phenomenon and not been reported in any other protozoa. This organism is exposed to various hostile environmental conditions, including changes in temperature, pH, and nutrient availability, which can lead to stress and damage to its cells. The formation of MGCs in Entamoeba is thought to be a survival strategy to cope with these adverse conditions. This organism forms MGCs through cell aggregation and fusion in response to osmotic and heat stress. The MGCs in Entamoeba are thought to have increased resistance to various stresses and can survive longer than normal cells under adverse conditions. This increased survival could be due to the presence of multiple nuclei, which could provide redundancy in case of DNA damage or mutations. Additionally, MGCs may play a role in the virulence of Entamoeba as they are found in the inflammatory foci of amoebic liver abscesses and other infections caused by Entamoeba. The presence of MGCs in these infections suggests that they may contribute to the pathogenesis of the disease. Overall, this article offers valuable insights into the intriguing phenomenon of MGC formation in Entamoeba. By unraveling the mechanisms behind this process and examining its implications, researchers can gain a deeper understanding of the complex biology of Entamoeba and potentially identify new targets for therapeutic interventions. The study of MGCs in Entamoeba serves as a gateway to exploring the broader field of cell fusion in various organisms, providing a foundation for future investigations into related cellular processes and their significance in health and disease.

SINGLE-CELL TRANSCRIPTOMIC PROFILING OF THE HYPERTENSION MOUSE BRAIN

Objective: Chronic hypertension has devastating effects on the brain, being the major cause of stroke and a leading cause of dementia. The alterations of cerebral blood vessels structure and vasoregulatory mechanisms leading by hypertension have been recognized for decades. However, the specific cellular and molecular mediators that drive these alterations remain unclear. Design and method: After 4 weeks of continuous administration of angiotensin II, we performed a single-cell transcriptomic analysis of brain cellulome. The brain cellular ecosystem in response to angiotensin II was analyzed, the network of cells that forms the mouse brain was profiled after a proinflammation stimulus that drives pathological brain vascular remodeling. Results: We analyzed the transcriptomes of 52,856 single cells (28,078 normal and 24,778 angiotensin II) derived from the brains of 10 normal and 12 angiotensin II mice, and compared all the cellular composition and transcriptomes of the whole brain cells. For all the major cell populations, we provide comprehensive datasets of genes and pathways whose transcriptional profiles change with hypertension. To reveal heterogeneity within each population, we grouped the cells into 14 classes based on the expression profile, lineage, function and anatomical organization. Of the 20718 total detected genes, 800 were significantly affected by hypertension in at least one cell type. Hypertensive- related cellular pathways and processes were also investigated, and we highlight changes in EC and EPC. Furthermore, the cellular responses to angiotensin II and the changes in intercellular communication were identified. Conclusions: These large-scale datasets provide a valuable resource for exploring the brain cellular landscape in health and after chronic cerebral vascular stress. These data provide insights into the cellular and molecular mechanisms that afford an additional discoveries of directed towards understanding the mechanisms by which hypertension disrupts cerebral blood vessels.

Role of Ceramides and Sphingolipids in Parkinson's Disease

Sphingolipids, including the basic ceramide, are a subset of bioactive lipids that consist of many different species. Sphingolipids are indispensable for proper neuronal function, and an increasing number of studies have emerged on the complexity and importance of these lipids in (almost) all biological processes. These include regulation of mitochondrial function, autophagy, and endosomal trafficking, which are affected in Parkinson’s disease (PD). PD is the second most common neurodegenerative disorder and is characterized by the loss of dopaminergic neurons. Currently, PD cannot be cured due to the lack of knowledge of the exact pathogenesis. Nonetheless, important advances have identified molecular changes in mitochondrial function, autophagy, and endosomal function. Furthermore, recent studies have identified ceramide alterations in patients suffering from PD, and in PD models, suggesting a critical interaction between sphingolipids and related cellular processes in PD. For instance, autosomal recessive forms of PD cause mitochondrial dysfunction, including energy production or mitochondrial clearance, that is directly influenced by manipulating sphingolipids. Additionally, endo-lysosomal recycling is affected by genes that cause autosomal dominant forms of the disease, such as VPS35 and SNCA. Furthermore, endo-lysosomal recycling is crucial for transporting sphingolipids to different cellular compartments where they will execute their functions.This review will discuss mitochondrial dysfunction, defects in autophagy, and abnormal endosomal activity in PD and the role sphingolipids play in these vital molecular processes.

Linking Pedobacter lusitanus NL19 volatile exometabolome with growth medium composition: what can we learn using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry?

Microbial metabolomics allows understanding and to comprehensively analyse metabolites, and their related cellular and metabolic processes, that are produced and released to the extracellular environment under specific conditions. In that regard, the main objective of this research is to understand the impact of culture media changes in the metabolic profile of Pedobacter lusitanus NL19 (NL19) and Pedobacter himalayensis MTCC 6384 (MTCC6384) and respective influence on the production of biotechnologically relevant compounds. Solid-phase microextraction combined with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry with time-of-flight analyser (GC × GC-ToFMS) was applied to comprehensively study the metabolites produced by NL19 and MTCC6384 both in tryptic soy broth 100% (TSB100) and tryptic soy broth with 25% casein peptone (PC25). A total of 320 metabolites were putatively identified, which belong to different chemical families: alcohols, aldehydes, esters, ethers, hydrocarbons, ketones, nitrogen compounds, sulphur compounds, monoterpenes, and sesquiterpenes. Metabolites that were statistically different from the control (sterile medium) were selected allowing for the construction of the metabolic profile of both strains. A set of 80 metabolites was tentatively associated to the metabolic pathways such as the metabolism of fatty acids, branched-chain aminoacids, phenylalanine, methionine, aromatic compounds, and monoterpene and sesquiterpene biosynthesis. This study allowed to better understand how slight changes of the culture media and thus the composition of nutrients impair the metabolic profile of bacteria, which may be further explored for metabolomics pipeline construction or biotechnological applications.

The emerging role of miR-20b in human cancer and other disorders: Pathophysiology and therapeutic implications.

miR-20b is a microRNA with diverse and somehow contradictory roles in the pathogenesis of human disorders, especially cancers. It has been known to be a tumor suppressor in colon cancer, renal cell carcinoma, prostate cancer, osteosarcoma and papillary thyroid cancer. In lung cancer and breast cancers, both tumor suppressor and oncogenic effects have been identified for this miRNA. Finally, in T cell leukemia, hepatocellular carcinoma, esophageal squamous cell carcinoma and cervical and gastric cancers, miR-20b is regarded as an oncogenic miRNA. In several types of cancer, dysregulation of miR-20b has been recognized as a predictive marker for patients' survival. Dysregulation of miR-20b has also been recognized in Alzheimer's disease, diabetic retinopathy, myocardial ischemia/infarction, chronic hepatitis B and multiple sclerosis. In the current review, we have summarized the miR-20b targets and related cellular processes. We have also provided a review of participation of this miRNA in different human disorders.

POLDIP3: At the Crossroad of RNA and DNA Metabolism.

POLDIP3 was initially identified as a DNA polymerase delta (Pol δ) interacting protein almost twenty years ago. Intriguingly, it also interacts with proteins involved in a variety of RNA related biological processes, such as transcription, pre-mRNA splicing, mRNA export, and translation. Studies in recent years revealed that POLDIP3 also plays critical roles in disassembling genome wide R-loop formation and activating the DNA damage checkpoint in vivo. Here, we review the functions of POLDIP3 in various RNA and DNA related cellular processes. We then propose a unified model to illustrate how POLDIP3 plays such a versatile role at the crossroad of the RNA and DNA metabolism.

Potential proteomic alteration in the brain of Tg(SOD1*G93A)1Gur mice: A new pathogenesis insight of amyotrophic lateral sclerosis.

The pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. The recent studies have suggested that the protein abnormalities could play some important roles in ALS because several protein mutations were found in individuals with this disease. However, proteins that are currently known to be associated with ALS only explain the pathogenesis of this disease in a minority of cases, thus, further screening is needed to identify other ALS-related proteins. In this study, we systematically analyzed and compared the brain proteomic alterations between a mouse model of ALS, the Tg(SOD1*G93A)1Gur model, and wild-type mice using isobaric tags for relative and absolute quantitation (iTRAQ) as well as bioinformatics methods. The results revealed some significant up- and downregulated proteins at the different developmental stages in the ALS-like mice as well as the possibly related cellular components, molecular functions, biological processes, and pathways in the development of ALS. Our results identified some possible proteins that participate in the pathogenesis of ALS as well as the cellular components that are damaged by these proteins, we additionally identified the molecular functions, the biological processes, and the pathways of these proteins as well as the molecules that are associated with these pathways. This study represents an important preliminary investigation of the role of proteomic abnormalities in the pathogenesis of ALS, both in human patients and other animal models. We present some novel findings that may serve as a basis for further investigation of abnormal proteins that are involved in the pathogenesis of ALS.

Influence of Surface Roughness on Biodegradability and Cytocompatibility of High-Purity Magnesium.

High-purity magnesium (Mg) is a promising biodegradable metal for oral and maxillofacial implants. Appropriate surface roughness plays a critical role in the degradation behavior and the related cellular processes of biodegradable Mg-based metals. Nevertheless, the most optimized surface roughness has been questionable, especially for Mg-based oral and maxillofacial implants. Three representative scales of surface roughness were investigated in this study, including smooth (Sa < 0.5 µm), moderately rough (Sa between 1.0–2.0 µm), and rough (Sa > 2.0 µm). The results indicated that the degradation rate of the Mg specimen in the cell culture medium was significantly accelerated with increased surface roughness. Furthermore, an extract test revealed that Mg with different roughness did not induce an evident cytotoxic effect. Nonetheless, the smooth Mg surface had an adversely affected cell attachment. Therefore, the high-purity Mg with a moderately rough surface exhibited the most optimized balance between biodegradability and overall cytocompatibility.

Qualitative lysine crotonylome analysis in the ovarian tissue of Harmonia axyridis (Pallas).

Lysine crotonylation (Kcr) is a newly discovered posttranslational modification (PTM), which has been studied at the proteomics level in a few species, with the study of Kcr in female fertility and in insect species is still lacking. Harmonia axyridis (Pallas) is a well-known beneficial insect used as a natural biological control agent against aphids in agriculture. Here, global Kcr identification in ovarian tissue of H. axyridis at diapause stage was performed to reveal potential roles for Kcr in H. axyridis ovarian cellular processes, female fertility and diapause regulation. In total, 3084 Kcr sites in 920 proteins were identified. Bioinformatic analyses revealed the distribution of these proteins in multiple subcellular localization categories and their involvement in diverse biological processes and metabolism pathways. Carbohydrate and energy metabolism related cellular processes including citric acid cycle, glycolysis and oxidative phosphorylation appeared be affected by Kcr modification. In addition, regulation of translation and protein biosynthesis may reflect Kcr involvement in diapause in H. axyridis, with Kcr affecting ribosome activities and amino acid metabolism. Moreover, Kcr modulation H. axyridis ovary development regulation may share some common mechanism with Kcr participation in some disease progression. These processes and pathways were uncovered under diapause stage, but possibly not enriched/specific for diapause stage due to limitations of qualitative proteomics experimental design. Our results informs on the potential for Kcr modifications to regulate female fertility and insect physiology.

Hereditary spastic paraplegia: new insights into clinical variability and spasticity-ataxia phenotype, and novel mutations.

Hereditary spastic paraplegias (HSPs), a genetically heterogeneous group of neurodegenerative diseases, have an incidence of around 3 to 9 individuals every 100,000. Due to the broad clinical and genetic variability of HSPs, it is challenging to diagnose the disorder quickly and precisely. Hereditary spastic ataxias (HSAs) and HSPs are overlapping diseases, and their intersection has been gradually identified by next-generation sequencing. The idea of the spasticity-ataxia phenotype (SAP) spectrum is further substantiated by the similarities in phenotypes and underlying genes in ataxias and inherited spastic paraplegias and the related cellular processes and disease mechanisms these disorders exhibit. Whole-exome sequencing was performed on the 25 spastic or spastic-ataxic gait patients. Twenty-two specific HSPs-HSAs-SAP mutations, including 14 novel mutations, were found in 25 cases from 18 Turkish and 2 Syrian families. This research discovers many novel hereditary spastic paraplegia (HSP) mutations and shows a robust genotype-phenotype heterogeneity in the disease. This research helped expand the clinical and molecular scope of HSP and clarified the concept of the spasticity-ataxia phenotype, further enhancing our understanding of the complicated form of HSP and its association with ataxia. Our data broadens the spectrum of HSPs and HSAs related gene mutations and provides insights for genotype-phenotype correlations for HSPs and HSAs.

Emerging solvatochromic push-pull dyes for monitoring the lipid order of biomembranes in live cells.

Solvatochromic dyes have emerged as a new class of fluorescent probes in the field of lipid membranes due to their ability to identify the lipid organization of biomembranes in live cells by changing the colour of their fluorescence. This type of solvatochromic function is useful for studying the heterogeneous features of biomembranes caused by the uneven distribution of lipids and cholesterols in live cells and related cellular processes. Therefore, a variety of advanced solvatochromic dyes have been rapidly developed over the last decade. To provide an overview of the works recently developed solvatochromic dyes have enabled, we herein present some solvatochromic dyes, with a particular focus on those based on pyrene and Nile red. As these dyes exhibit preferable photophysical properties in terms of fluorescence microscopy applications and unique distribution/localization in cellular compartments, some have already found applications in cell biological and biophysical studies. The goal of this review is to provide information to researchers who have never used solvatochromic dyes or who have not discovered applications of such dyes in biological studies.