Expression Patterns Research Articles

A new integrative analysis of histopathology and single cell RNA-seq reveals the CCL5 mediated T and NK cell interaction with vascular cells in idiopathic pulmonary arterial hypertension

BackgroundInflammation and dysregulated immunity play vital roles in idiopathic pulmonary arterial hypertension (IPAH), while the mechanisms that initiate and promote these processes are unclear.MethodsTranscriptomic data of lung tissues from IPAH patients and controls were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) and functional enrichment analysis were combined with a hemodynamically-related histopathological score to identify inflammation-associated hub genes in IPAH. The monocrotaline-induced rat model of pulmonary hypertension was utilized to confirm the expression pattern of these hub genes. Single-cell RNA-sequencing (scRNA-seq) data were used to identify the hub gene-expressing cell types and their intercellular interactions.ResultsThrough an extensive bioinformatics analysis, CXCL9, CCL5, GZMA and GZMK were identified as hub genes that distinguished IPAH patients from controls. Among these genes, pulmonary expression levels of Cxcl9, Ccl5 and Gzma were elevated in monocrotaline-exposed rats. Further investigation revealed that only CCL5 and GZMA were highly expressed in T and NK cells, where CCL5 mediated T and NK cell interaction with endothelial cells, smooth muscle cells, and fibroblasts through multiple receptors.ConclusionsOur study identified a new inflammatory pathway in IPAH, where T and NK cells drove heightened inflammation predominantly via the upregulation of CCL5, providing groundwork for the development of targeted therapeutics.

Cross-centroid ripple pattern for facial expression recognition

AbstractIn this paper, we propose a new feature descriptor Cross-Centroid Ripple Pattern (CRIP) for facial expression recognition. CRIP encodes the transitional pattern of a facial expression by incorporating a cross-centroid relationship between two ripples located at radius r1 and r2 respectively. These ripples are generated by dividing the local neighborhood region into subregions. Thus, CRIP has the ability to preserve macro and microstructural variations in an extensive region, which enables it to deal with side views and spontaneous expressions. Furthermore, gradient information between cross centroid ripples provides strength to capture prominent edge features in active patches: eyes, nose, and mouth, that define the disparities between different facial expressions. Cross-centroid information also provides robustness to irregular illumination. Moreover, CRIP utilizes the averaging behavior of pixels at subregions that yields robustness to deal with noisy conditions. The performance of the proposed descriptor is evaluated on seven comprehensive expression datasets consisting of challenging conditions such as age, pose, ethnicity, and illumination variations. The experimental results show that our descriptor consistently achieved a better accuracy rate as compared to existing state-of-the-art approaches.

A new prognostic model based on gamma-delta T cells for predicting the risk and aiding in the treatment of clear cell renal cell carcinoma

BackgroundccRCC is the prevailing form of RCC, accounting for the majority of cases. The formation of cancer and the body's ability to fight against tumors are strongly connected to Gamma delta (γδ) T cells.MethodsWe examined and analyzed the gene expression patterns of 535 individuals diagnosed with ccRCC and 72 individuals serving as controls, all sourced from the TCGA-KIRC dataset, which were subsequently validated through molecular biology experiments.ResultsIn ccRCC, we discovered 304 module genes (DEGRGs) that were ex-pressed differentially and linked to γδ T cells. A risk model for ccRCC was constructed using 13 differentially DEGRGs identified through univariate Cox and LASSO regression analyses, which were found to be associated with prognosis. The risk model exhibited outstanding performance in both the training and validation datasets. The comparison of immune checkpoint inhibitors and the tumor immune microenvironment between the high- and low-risk groups indicates that immunotherapy could lead to positive results for low-risk patients. Moreover, the inhibition of ccRCC cell proliferation, migration, and invasion was observed in cell culture upon knocking down TMSB10, a gene associated with different types of cancers.ConclusionsIn summary, we have created a precise predictive biomarker using a risk model centered on γδ T cells, which can anticipate clinical results and provide direction for the advancement of innovative targeted therapies.

Expression and significance of pin1 in the wound healing.

The aim of this study is to delineate the expression patterns of prolyl cis-trans isomerase NIMA-interacting protein 1 (Pin1), Glial cell-derived neurotrophic factor (GDNF), and Angiotensin II (ANG II) during the process of wound repair, and to ascertain the effects of Pin1, GDNF, and ANG II on the healing of wounds in a rat model. A total of 18 rats were allocated into three groups-sham (control), DMSO (vehicle control), and Pin1 inhibitor (treatment with juglone)-with six animals in each group. An animal model of wound healing was established, followed by the intraperitoneal administration of juglone. Tissue samples from the wounds were subsequently collected for histopathological evaluation. Expression levels of Pin1, GDNF, and Ang II were quantified. In addition, an in vitro model of wound healing was created using human umbilical vein endothelial cells (HUVEC), to assess cell proliferation, migration, and tube formation under conditions of juglone pre-treatment. The expression levels of Pin1, GDNF, and ANG II were notably elevated on 7-, and 10- days post-wound compared to those measured on 3-day. Contrastingly, pre-treatment with juglone significantly inhibited the expression of these molecules. Histological analyses, including HE (Hematoxylin and Eosin), Masson's trichrome, and EVG (Elastic van Gieson) staining, demonstrated that vascular angiogenesis, as well as collagen and elastin deposition, were substantially reduced in the juglone pre-treated group when compared to the normal group. Further, immunohistochemical analysis revealed a considerable decrease in CD31 expression in the juglone pre-treatment group relative to the normal control group. Pin1 serves as a pivotal facilitator of wound repair. The findings indicate that the modulation of Pin1, GDNF, and ANG II expression impacts the wound healing process in rats, suggesting potential targets for therapeutic intervention in human wound repair.

Mir-182-5p regulates all three phases of inflammation, proliferation, and remodeling during cutaneous wound healing.

Wound healing is a highly programmed process, in which any abnormalities result in scar formation. MicroRNAs are potent regulators affecting wound repair and scarification. However, the function of microRNAs in wound healing is not fully understood. Here, we analyzed the expression and function of microRNAs in patients with cutaneous wounds. Cutaneous wound biopsies from patients with either hypertrophic scarring or normal wound repair were collected during inflammation, proliferation, and remodeling phases. Fourteen candidate microRNAs were selected for expression analysis by qRT-PCR. The expression of genes involved in inflammation, angiogenesis, proliferation, and migration were measured using qRT-PCR. Cell cycle and scratch assays were used to explore the proliferation and migration rates. Flow cytometry analysis was employed to examine TGF-β, αSMA and collagen-I expression. Target gene suggestion was performed using Enrichr tool. The results showed that miR-16-5p, miR-152-3p, miR-125b-5p, miR-34c-5p, and miR-182-5p were revealed to be differentially expressed between scarring and non-scarring wounds. Based on the expression patterns obtained, miR-182-5p was selected for functional studies. miR-182-5p induced RELA expression synergistically upon IL-6 induction in keratinocytes and promoted angiogenesis. miR-182-5p prevented keratinocyte migration, while overexpressed TGF-β3 following induction of inflammation. Moreover, miR-182-5p enhanced fibroblast proliferation, migration, differentiation, and collagen-1 expression. FoxO1 and FoxO3 were found to potentially serve as putative gene targets of miR-182-5p. In conclusion, miR-182-5p is differentially expressed between scarring and non-scarring wounds and affect the behavior of cells involved in cutaneous wound healing. Deregulated expression of miR-182-5p adversely affects the proper transition of wound healing phases, resulting in scar formation.

CircRNA hsa_circ_0069,399 as a potential clinical prognostic marker in laryngeal squamous cell carcinoma

ObjectiveCircular RNAs (circRNAs) significantly influence the invasion, metastasis, gene expression, proliferation, and apoptosis of tumor cells. However, the roles of circRNAs in laryngeal squamous cell carcinoma (LSCC) remain largely unexplored. This study aims to examine circRNA expression patterns in LSCC and adjacent non-tumorous tissues, with the goal of uncovering potential biomarkers for LSCC. MethodsTissue samples were collected from both the tumor and adjacent normal tissues of ten patients who had undergone surgical resection. The profiling of circRNAs was conducted through transcriptomic sequencing and analytical bioinformatics approaches. A ternary regulatory network based on the competitive endogenous RNA (ceRNA) hypothesis was established, linking target circRNAs to clinical immunohistochemical parameters for comparison. Verification of target circRNAs in LSCC tissues was performed using quantitative real-time PCR (RT-qPCR), whereas target mRNAs were analyzed through immunohistochemistry. ResultsA total of 126 significantly different circRNAs were identified, including 40 up-regulated genes and 86 down-regulated genes. Furthermore, 92 circRNA-miRNA-mRNA regulatory relationship axes related to clinical immunohistochemical indicators were found based on 5 candidate circRNAs. Interestingly, all axes related to the target genes MKI67 and TP53 were found to compete with the same circRNA: hsa_circ_0069,399. Further verification confirmed that the hsa_circ_0069,399 expression was overtly upregulated in tumor tissues from LSCC patients, which was consistent with the sequencing results. Conclusionhsa_circ_0069,399 could be a potential prognostic marker for LSCC.

MSGD: a manually curated database of genomic, transcriptomic, proteomic and drug information for multiple sclerosis.

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. 'Omics' technologies (genomics, transcriptomics, proteomics) and associated drug information have begun reshaping our understanding of multiple sclerosis. However, these data are scattered across numerous references, making them challenging to fully utilize. We manually mined and compiled these data within the Multiple Sclerosis Gene Database (MSGD) database, intending to continue updating it in the future. We screened 5485 publications and constructed the current version of MSGD. MSGD comprises 6255 entries, including 3274 variant entries, 1175 RNA entries, 418 protein entries, 313 knockout entries, 612 drug entries and 463 high-throughput entries. Each entry contains detailed information, such as species, disease type, detailed gene descriptions (such as official gene symbols), and original references. MSGD is freely accessible and provides a user-friendly web interface. Users can easily search for genes of interest, view their expression patterns and detailed information, manage gene sets and submit new MS-gene associations through the platform. The primary principle behind MSGD's design is to provide an exploratory platform, aiming to minimize filtration and interpretation barriers while ensuring highly accessible presentation of data. This initiative is expected to significantly assist researchers in deciphering gene mechanisms and improving the prevention, diagnosis and treatment of MS. Database URL: http://bio-bigdata.hrbmu.edu.cn/MSGD.

XCR1: A promising prognostic marker that pinpoints targeted and immune-based therapy in hepatocellular carcinoma

ObjectivesThe lymphotactin receptor X–C motif chemokine receptor 1 (XCR1) is an essential member of the chemokine receptor family and is related to tumor development and progression. Nevertheless, further investigation is required to explore its expression patterns, prognostic values, and functions related to target or immune therapies in patients with hepatocellular carcinoma (HCC). Materials and methodsThe differential expression patterns of XCR1 and its prognostic influences were performed through The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Subsequently, immunohistochemistry (IHC) staining and univariate and multivariate Cox regressions were performed to validate the prognostic values in different subgroups. Furthermore, the potential roles of XCR1 in predicting target and immune therapeutic responses were also investigated. ResultsIncreased expression level of XCR1 was associated with favorable overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis revealed that a high expression level of XCR1 or positive immune cell proportion score (iCPS) were associated with favorable OS in the HCC patients with favorable tumor characteristics. In addition, the enhanced XCR1 expression was associated with the tumor environment scores, immune cell infiltration levels, and the expression levels of immune checkpoint genes. Further analysis revealed that improved expression of XCR1 was linked to better OS and RFS in HCC patients who received sorafenib. ConclusionThis study identified that XCR1 is a valuable prognostic biomarker in the HCC population, especially in those with favorable tumor characteristics. The combination of iCPS status and BCLC status has a synergistic effect on stratifying patients' OS and RFS. Further analyses showed that XCR1 has the potential ability to predict treatment responses to sorafenib and immune-based therapies.

Developmental stage dependent effects of posterior and germline regeneration on sexual maturation in Platynereis dumerilii

Regeneration, regrowing lost and injured body parts, is an ability that generally declines with age or developmental transitions (i.e. metamorphosis, sexual maturation). Regeneration is also an energetically costly process, and trade-offs occur between regeneration and other costly processes such as growth, or sexual reproduction. Here we investigate the interplay of regeneration, reproduction, and developmental stage in the segmented worm Platynereis dumerilii. P. dumerilii can regenerate its whole posterior body axis, along with its reproductive cells, thereby having to carry out the two costly processes (somatic and germ cell regeneration) after injury. We specifically examine how developmental stage affects the success of germ cell regeneration and sexual maturation in developmentally young versus developmentally old organisms. We hypothesized that developmentally younger individuals (i.e. with gametes in early mitotic stages) will have higher regeneration success than the individuals at developmentally older stages (i.e. with gametes undergoing meiosis and maturation). Surprisingly, older amputated worms grew faster and matured earlier than younger amputees. To analyze germ cell regeneration during and after posterior regeneration, we used Hybridization Chain Reaction for the germline marker vasa. We found that regenerated worms start repopulating new segments with germ cell clusters as early as 14 days post amputation. In addition, vasa expression is observed in a wide region of newly-regenerated segments, which appears different from expression patterns during normal growth or regeneration in worms before gonial cluster expansion.

Cytological Observation and RNA-Seq Analyses Reveal miR9564 and Its Target Associated with Pollen Sterility in Autotetraploid Rice.

Understanding the regulation of autotetraploid sterility is essential for harnessing the strong advantages in genomic buffer capacity, biodiversity, and heterosis of autotetraploid rice. miRNAs play crucial roles in fertility regulation, yet information about their reproductive roles and target genes in tetraploid rice remains limited. Here, we used three tetraploid lines, H1 (fertile), HF (fertile), and LF (sterile), to investigate cytological features and identify factors associated with autotetraploid sterility. LF showed abnormal meiosis, resulting in low pollen fertility and viability, ultimately leading to scarce fertilization and a low-seed setting compared to H1 and HF. RNA-seq revealed 30 miRNA-candidate target pairs related to autotetraploid pollen sterility. These pairs showed opposite expression patterns, with differential expression between fertile lines (H1 and HF) and the sterile line (LF). qRT-PCR confirmed that miR9564, miR528, and miR27874 were highly expressed in the anthers of H1 and HF but not in LF, while opposite results were obtained in their targets (ARPS, M2T, and OsRPC53). Haplotype and expression pattern analyses revealed that ARPS was specifically expressed in lines with the same haplotype of MIR9564 (the precursor of miR9564) as LF. Furthermore, the Dual-GFP assay verified that miR9564 inhibited the fluorescence signal of ARPS-GFP. The over-expression of ARPS significantly decreased the seed setting rate (59.10%) and pollen fertility (50.44%) of neo-tetraploid rice, suggesting that ARPS plays important roles in autotetraploid pollen sterility. This study provides insights into the cytological characteristic and miRNA expression profiles of tetraploid lines with different fertility, shedding light on the role of miRNAs in polyploid rice.

GCNT3 Promotes Hepatocellular Carcinoma Progression and EMT by Activating the PI3K/AKT Pathway.

Primary liver cancer, specifically hepatocellular carcinoma (HCC), is a major global health concern. GCNT3 has been identified as an oncogene in various human malignancies. This investigation aimed to discover the GCNT3 function in HCC. The present study employed integrated bioinformatics analyses to assess the expression pattern, prognostic implications, and putative function of GCNT3 in HCC. Transwell flow cytometry, CCK-8, and wound healing assays were performed to examine HCC cell growth, cell cycle, apoptosis, invasion, and migration. In addition, the epithelial-mesenchymal transition (EMT) markers and PI3K/AKT mechanism markers were examined via western blot analysis to elucidate the underlying mechanisms. In HCC, GCNT3 was significantly overexpressed, which was connected with enhanced tumor aggressiveness and an unfavorable prognosis of individuals. In vitro experiments demonstrated that elevated levels of GCNT3 promoted cell growth, migration, cell cycle development, and invasion, in addition to EMT, while suppressing apoptosis. Conversely, knockdown of GCNT3 exerted the opposite effects. GCNT3 overexpression increased PI3K/AKT phosphorylation in HCC cells, and LY294002 counteracted the impacts of upregulated GCNT3 on cell cycle, migration, invasion, proliferation, and EMT in HCC. The investigation showed that GCNT3 may enhance HCC progression and EMT by stimulating PI3K/AKT mechanism.

Proteomic reference map for sarcopenia research: mass spectrometric identification of key muscle proteins located in the sarcomere, cytoskeleton and the extracellular matrix.

Sarcopenia of old age is characterized by the progressive loss of skeletal muscle mass and concomitant decrease in contractile strength. Age-related skeletal muscle dysfunctions play a key pathophysiological role in the frailty syndrome and can result in a drastically diminished quality of life in the elderly. Here we have used mass spectrometric analysis of the mouse hindlimb musculature to establish the muscle protein constellation at advanced age of a widely used sarcopenic animal model. Proteomic results were further analyzed by systems bioinformatics of voluntary muscles. In this report, the proteomic survey of aged muscles has focused on the expression patterns of proteins involved in the contraction-relaxation cycle, membrane cytoskeletal maintenance and the formation of the extracellular matrix. This includes proteomic markers of the fast versus slow phenotypes of myosin-containing thick filaments and actin-containing thin filaments, as well as proteins that are associated with the non-sarcomeric cytoskeleton and various matrisomal layers. The bioanalytical usefulness of the newly established reference map was demonstrated by the comparative screening of normal versus dystrophic muscles of old age, and findings were verified by immunoblot analysis.

Discovery of a T cell proliferation-associated regulator signature correlates with prognosis risk and immunotherapy response in bladder cancer.

The efficacy of immunotherapy is heavily influenced by T cell activity. This study aimed to examine how T cell proliferation regulators can predict the prognosis and response to immunotherapy in patients with bladder cancer (BCa). T cell proliferation-related subtypes were determined by employing the non-negative matrix factorization (NMF) algorithm that analyzed the expression patterns of T cell proliferation regulators. Subtypes were assessed for variations in prognosis, immune infiltration, and functional behaviors. Subsequently, a risk model related to T cell proliferation was created through Cox and Lasso regression analyses in the TCGA cohort and then confirmed in two GEO cohorts and an immunotherapy cohort. BCa patients were categorized into two subtypes (C1 and C2) according to the expression profiles of 31T cell proliferation-related genes (TRGs) with distinct prognoses and immune landscapes. The C2 subtype had a shorter overall survival (OS), with higher levels of M2 macrophage infiltration, and the activation of cancer-related pathways than the C1 subtype. Following this, thirteen prognosis-related genes that were involved in T cell proliferation were utilized to create the prognostic signature. The model's predictive accuracy was confirmed by analyzing both internal and external datasets. Individuals in the high-risk category experienced a poorer prognosis, increased immunosuppressive factors in the tumor microenvironment, and diminished responses to immunotherapy. Additionally, the immunotherapeutic prediction efficacy of the model was further confirmed by an immunotherapy cohort (anti-PD-L1 in the IMvigor210 cohort). Our study characterized two subtypes linked to T cell proliferation in BCa patients with distinct prognoses and tumor microenvironment (TME) patterns, providing new insights into the heterogeneity of T cell proliferation in BCa and its connection to the immune landscape. The signature has prospective clinical implications for predicting outcomes and may help physicians to select prospective responders who prioritize current immunotherapy.

SLC7A5 correlated with malignancies and immunotherapy response in bladder cancer

BackgroundMetabolic reprogramming contributes to bladder cancer development. This study aimed to understand the role of SLC7A5 in bladder cancer.MethodsWe systematically analyzed the correlation between SLC7A5 and bladder cancer through various approaches, including bioinformatics, western blotting, cell cycle analysis, cell proliferation assays, and invasion experiments. We also investigated the immunological features within the tumor microenvironment (TME), encompassing cancer immune cycles, immune modulators, immune checkpoints, tumor-infiltrating immune cells (TIIC), T cell inflammation scores, and treatment responses. Additionally, for a comprehensive assessment of the expression patterns and immunological roles of SLC7A5, pan-cancer analysis was performed using cancer genomics datasets.ResultsSLC7A5 was associated with adverse prognosis in bladder cancer patients, activating the Wnt pathway and promoting bladder cancer cell cycle progression, proliferation, migration, and invasion. Based on the evidence that SLC7A5 positively correlated with immunomodulators, TIIC, the cancer immune cycle, immune checkpoint and T cell inflammation scores, we also found that SLC7A5 was associated with the inflammatory tumor immune microenvironment. EGFR-targeted therapy, cancer immunotherapy, and radiation therapy were effective for patients with high SLC7A5 expression in bladder cancer. Low SLC7A5 patients were, however, sensitive to targeted therapies and anti-angiogenic therapy, such as blocking β-catenin network, PPAR-γ and FGFR3 signaling. Anti-SLC7A5 combined with cancer immunotherapy may have greater effectiveness than either therapy alone. Furthermore, we observed specific overexpression of SLC7A5 in TME of various cancers.ConclusionSLC7A5 can predict therapeutic response to immunotherapy, radiotherapy and chemotherapy in bladder cancer patients. Targeting SLC7A5 in combination with immunotherapy may be a potentially appropriate treatment option.

Enhancing motor functional recovery in spinal cord injury through pharmacological inhibition of Dickkopf-1 with BHQ880 antibody

BackgroundMounting experimental evidence has underscored the remarkable role played by the Wnt family of proteins in the spinal cord functioning and therapeutic potential in spinal cord injury (SCI). We aim to provide a therapeutic prospect associated with the modulation of canonical Wnt signaling, examining the spatio-temporal expression pattern of Dickkopf-1 (Dkk1) and its neutralization after SCI. We employ an intraparenchymal injection of the clinically validated Dkk1-blocking antibody, BHQ880, to elucidate its effects in SCI. MethodsA rat model of contusion SCI was used. Histological analyses were performed, wherein Dkk1 protein was sought, and ELISA analyses were employed for Dkk1 detection in cerebrospinal fluid and serum. To ascertain the BHQ880 therapeutic effect, rats were subjected to SCI and then injected with the antibody in the lesion epicenter 24 hours post-injury (hpi). Subsequent evaluation of motor functional recovery extended up to 56 days post-injury (dpi). qRT-PCR and histological analyses were conducted. ResultsWe demonstrate the presence of Dkk1 in the healthy rat spinal cord, with pronounced alterations observed following injury, primarily concentrated in the epicenter regions. Notably, a significative upregulation of Dkk1 was detected at 24 hpi, peaking at 3 dpi and remaining elevated until 42 dpi. Moreover, we revealed that early administration of BHQ880 considerably improved motor functional recovery, promoted preservation of myelinated tissue, and reduced astroglial and microglia/macrophage reactivity. Furthermore, there was a decrease in the acute expression of different inflammatory genes. ConclusionsCollectively, our findings highlight the therapeutic potential of BHQ880 treatment in the context of SCI.

The Specific ROCK2 Inhibitor KD025 Alleviates Glycolysis through Modulating STAT3-, CSTA- and S1PR3-Linked Signaling in Human Trabecular Meshwork Cells.

To investigate the biological significance of Rho-associated coiled-coil-containing protein kinase (ROCK) 2 in the human trabecular meshwork (HTM), changes in both metabolic phenotype and gene expression patterns against a specific ROCK2 inhibitor KD025 were assessed in planar-cultured HTM cells. A seahorse real-time ATP rate assay revealed that administration of KD025 significantly suppressed glycolytic ATP production rate and increased mitochondrial ATP production rate in HTM cells. RNA sequencing analysis revealed that 380 down-regulated and 602 up-regulated differentially expressed genes (DEGs) were identified in HTM cells treated with KD025 compared with those that were untreated. Gene ontology analysis revealed that DEGs were more frequently related to the plasma membrane, extracellular components and integral cellular components among cellular components, and related to signaling receptor binding and activity and protein heterodimerization activity among molecular functions. Ingenuity Pathway Analysis (IPA) revealed that the detected DEGs were associated with basic cellular biological and physiological properties, including cellular movement, development, growth, proliferation, signaling and interaction, all of which are associated with cellular metabolism. Furthermore, the upstream regulator analysis and causal network analysis estimated IL-6, STAT3, CSTA and S1PR3 as possible regulators. Current findings herein indicate that ROCK2 mediates the IL-6/STAT3-, CSTA- and S1PR3-linked signaling related to basic biological activities such as glycolysis in HTM cells.

CircRNA Interference Pathway: A New Target for Intervention in Different Stages of Heart Failure.

Cardio-cerebrovascular disease has seen a rapid rise in recent years, with Heart Failure (HF) -- a terminal stage of various cardiovascular diseases -- also on the rise. HF has a complex pathogenesis involving multiple factors, such as inflammation, fibrosis, and oxidative stress. Due to its unique reverse shear mechanism, HF exhibits distinct expression patterns across different diseases. CircRNA has been linked to conditions like cancer, diabetes, and osteoarthritis. This article briefly introduces the mechanisms of circRNA biogenesis and its associated biological functions, focusing on CircSLC8A1-1, CircRNA_000203, and others at the early stage of HF, CircRNA PAN3, CircRNA (ACR), and others during the progression of HF, and CircHIPK3, CircNfix, and others at the end stage of HF. These circRNAs play a participatory role in the exact mechanism. As a research method, circRNA can be utilized to study the pathogenesis of heart failure and serve as a target for drug discovery and development. Therefore, circRNA's ability to mark the disease at different stages has significant guiding implications for HF monitoring, treatment, and prognosis.

Rephrasing the 'David-Goliath' story in the field of diabetes.

Diabetes Mellitus has become a serious threat to public health. This non-communicable disease is spreading like wildfire to shape in the form of a global pandemic. It affects several organs during silent progression in the human body. The pathophysiological fallouts associate dysregulation of numerous cellular pathways. MicroRNAs have emerged as potent gene expression regulators by post-transcriptional mechanisms in the last two decades or so. Many microRNAs display differential expression patterns under hyperglycemia affecting coupled cellular signaling cascades. The present article attempts to unfold the involvement of microRNAs as biomarkers in diabetic conditions in current scenarios identifying their therapeutic significance.

Transcriptional profiling of retinal astrocytes identifies a specific marker and points to functional specialization.

Astrocyte heterogeneity is an increasingly prominent research topic, and studies in the brain have demonstrated substantial variation in astrocyte form and function, both between and within regions. In contrast, retinal astrocytes are not well understood and remain incompletely characterized. Along with optic nerve astrocytes, they are responsible for supporting retinal ganglion cell axons and an improved understanding of their role is required. We have used a combination of microdissection and Ribotag immunoprecipitation to isolate ribosome-associated mRNA from retinal astrocytes and investigate their transcriptome, which we also compared to astrocyte populations in the optic nerve. Astrocytes from these regions are transcriptionally distinct, and we identified retina-specific astrocyte genes and pathways. Moreover, although they share much of the "classical" gene expression patterns of astrocytes, we uncovered unexpected variation, including in genes related to core astrocyte functions. We additionally identified the transcription factor Pax8 as a highly specific marker of retinal astrocytes and demonstrated that these astrocytes populate not only the retinal surface, but also the prelaminar region at the optic nerve head. These findings are likely to contribute to a revised understanding of the role of astrocytes in the retina.

Genome-Wide Identification and Multi-Stress Response Analysis of the DABB-Type Protein-Encoding Genes in Brassica napus.

The DABB proteins, which are characterized by stress-responsive dimeric A/B barrel domains, have multiple functions in plant biology. In Arabidopsis thaliana, these proteins play a crucial role in defending against various pathogenic fungi. However, the specific roles of DABB proteins in Brassica napus remain elusive. In this study, 16 DABB encoding genes were identified, distributed across 10 chromosomes of the B. napus genome, which were classified into 5 branches based on phylogenetic analysis. Genes within the same branch exhibited similar structural domains, conserved motifs, and three-dimensional structures, indicative of the conservation of BnaDABB genes (BnaDABBs). Furthermore, the enrichment of numerous cis-acting elements in hormone induction and light response were revealed in the promoters of BnaDABBs. Expression pattern analysis demonstrated the involvement of BnaDABBs, not only in the organ development of B. napus but also in response to abiotic stresses and Sclerotinia sclerotiorum infection. Altogether, these findings imply the significant impacts of BnaDABBs on plant growth and development, as well as stress responses.