Hasil untuk "Cytology"

Wang Yuqiang, Zhang Ziyan, Sun Xuedi et al.

Bone regeneration is a highly coordinated process shaped by the interplay between immune responses and osteogenic mechanisms. Immune cells such as neutrophils, macrophages, T cells, and B cells dynamically regulate the local microenvironment through cytokine secretion and signaling pathways, thereby influencing osteogenesis, angiogenesis and bone remodeling, while dysregulated or prolonged inflammation can disrupt healing. Growing evidence has highlighted the potential of leveraging immunomodulation to enhance bone repair. This review synthesizes recent progress in immunoregulatory strategies by comparing cellular therapies, molecular interventions and biomaterial-based approaches in terms of their mechanisms, their effects on osteogenesis and angiogenesis, and their translational potential. Particular emphasis is placed on immune cell specific signaling pathways, biomaterial design parameters including surface topography, porosity, ion release and stiffness, and emerging technologies such as immune responsive hydrogels, programmable scaffolds and exosome based delivery systems. Current findings indicate that mesenchymal stem cells and regulatory T cells not only provide progenitor sources but also reshape the immune milieu through paracrine factors and exosomes; cytokines, small molecules, microRNAs and pro resolving mediators effectively modulate inflammatory cascades to promote vascularized bone formation; and immunomodulatory biomaterials enable spatiotemporal regulation of macrophage polarization, particularly the transition from the pro inflammatory M1 phenotype to the reparative M2 phenotype. Collectively, these advances highlight that bone repair is fundamentally an immunologically driven process, and integrating temporal immune regulation with emerging therapeutic platforms offers a promising pathway toward precise and personalized bone regeneration.

Runxiao Luo, Tao Zhong, Linjie Wang et al.

Skeletal muscle myogenesis is a crucial factor influencing meat production in livestock. MicroRNAs (miRNAs) play a significant role in skeletal muscle myogenesis. The objective of this study was to identify key miRNAs involved in the process of goat skeletal muscle satellite cell (MuSC) differentiation into myotubes. We performed miRNA expression profiling analysis during the proliferation phase (cultured in growth medium, GM) and the differentiation phase (cultured in differentiation medium for 1 day and 5 days, classified as DM1 and DM5, respectively) of goat skeletal muscle satellite cells (MuSCs). A total of 1846 miRNAs were identified in MuSC samples, of which 677 differentially expressed miRNAs (DEmiRNAs) were screened through pairwise comparisons across three groups (GM vs. DM1, GM vs. DM5, and DM1 vs. DM5), and the results were further confirmed by a quantitative real-time PCR assay. Time-series expression profiling facilitated the categorization of the DEmiRNAs into eight distinct clusters, one of which demonstrated a significantly downregulated expression pattern (<i>p</i> < 0.05). Functional enrichment analysis revealed that the target genes of DEmiRNAs are involved in several pathways that are critical for myogenesis, including Hippo, TGF-β, MAPK and cell adhesion molecules. Interaction network analysis identified 19 miRNAs and 56 mRNAs associated with muscle cell development. Notably, novel-m0047-5p emerged as a key regulator, exhibiting strong negative correlations (r = −0.88 to −0.89, q < 0.01) with muscle-related target genes FOSB, CPT1B, and MYOZ2. These findings elucidate miRNA-mediated regulatory networks in goat myogenesis and provide candidate molecular targets for genetic improvement of meat production traits.

Mohamad Moustafa Ali, Yuka Itoh, Aisha Mariama Pereira Badji et al.

Abstract Cancer signaling encompasses a wide array of entangled molecular cascades that promote oncogenic progression and counteract the effect of tumor suppressors. Transforming growth factor β (TGFβ) induces complex and stage-dependent effects throughout tumor progression. During pre-malignant hyperplastic growth, TGFβ restricts cell proliferation and inflammation, while on the other hand, TGFβ promotes migration and distal metastasis of cancer cells. To dissect the temporal chromatin-based transcriptional response to TGFβ, we employed 3D culture models of isogenic human breast epithelial cells, exemplified by non-oncogenic MCF-10A (MI) and their HRAS-transformed counterpart (MII). Genome-wide chromatin accessibility profiling revealed an extensive chromatin opening induced by TGFβ at transcription start sites and enhancer elements in both models, with a marked enrichment of SOX4 binding motifs in oncogenic cells. Transcriptomic analyses unexpectedly revealed the upregulation of DNA replication and DNA damage response pathways, following TGFβ stimulation of oncogenic MII 3D cultures. Canonical TGFβ-driven programs, including epithelial-mesenchymal transition and metabolic reprogramming, were activated in both models. Notably, single-cell RNA-seq of primary breast tumors confirmed co-expression of SOX4 and cell cycle regulators. Mechanistically, we show that TGFβ induces the interaction between the MH2 domain of SMAD3 and the intrinsically disordered regions of SOX4, co-activating downstream gene targets. Validating the genome-wide analyses, we found that resistance of breast cancer cells to the CDK4/6 inhibitor palbociclib conferred by TGFβ stimulation was functionally dependent on SOX4. Collectively, our findings reveal an apparent oncogenic function of TGFβ in promoting cell cycle progression and drug resistance through SOX4, highlighting the pro-tumorigenic role of TGFβ signaling in breast cancer progression.

Joaquín Marco-Brualla, Oscar Gonzalo, Gemma Azaceta et al.

Since its discovery, the BTK inhibitor ibrutinib has redefined the standard treatments for hematological cancers, such as chronic lymphocytic leukemia (CLL). However, concerns exist regarding its secondary effects in humans and its occasional lack of efficacy in certain malignancies. Therefore, combined therapies with ibrutinib have emerged as promising new approaches. In this study, we aimed to explore its therapeutic potential through different approaches. For this purpose, we combined this drug with the BH3 mimetics ABT-199 and ABT-737, which inhibit anti-apoptotic members of the Bcl-2 family, and with the PDK1 inhibitor dichloroacetate (DCA), respectively. As cell models, we used ex vivo samples from patients and also selected the in vitro CLL cell line Mec-1, generating two sub-lines overexpressing Bcl-XL and Mcl-1, a common feature in this cancer. Results demonstrated a synergistic effect for both approaches, in all tumor cells tested, for both cytostatic and cytotoxic effects. Mechanistically, the expression of Bcl-2-family proteins was explored, exhibiting increases in pro-apoptotic, but also in anti-apoptotic, proteins upon ibrutinib treatment and a relative increase in the amount of the pro-apoptotic protein PUMA after treatment with DCA. Our data provides new insights into combined therapies with ibrutinib for CLL, which further expands our knowledge and the potential of this drug for cancer treatment.

Minghan Qiu, Zhanhua Gao, Mengran Tian et al.

Abstract Background Breast cancer is one of the most common malignancies globally. Despite advancements in treatment, efficacy for certain subtypes such as triple-negative breast cancer (TNBC) remains limited. Immunotherapy has provided new hope for advanced breast cancer, particularly triple-negative breast cancer (TNBC), though its effectiveness varies by tumor type and patient differences. LIMCH1, a relatively understudied LIM-domain protein, has been linked to cytoskeletal regulation and various cancers, including lung, cervical, and renal carcinoma. This study aims to investigate LIMCH1 expression and its impact in breast cancer. Methods The prognostic role of LIMCH1 in multiple cancers was analyzed using the TCGA database, and its expression in breast cancer was validated through immunohistochemistry (IHC) on breast cancer tissue microarrays. LIMCH1 overexpression and knockdown TNBC cell lines were constructed, and CCK-8, colony formation, transwell migration, and wound healing assays were performed to assess the effect of LIMCH1 on cell proliferation and migration. PD-L1 expression and selected immune-related proteins, such as CD3, CD4, CD8, and p-ERK1/2, were evaluated by flow cytometry, immunofluorescence, or Western blotting. A mouse allograft model was established to evaluate LIMCH1’s role in tumor growth and T-cell infiltration within the TIME. Results LIMCH1 was highly expressed in breast cancer and associated with poor prognosis. Bioinformatics analysis revealed that high LIMCH1 expression correlates with an immunosuppressive state. Functional assays showed that LIMCH1 overexpression promoted proliferation and migration, while knockdown inhibited these phenotypes. Mechanistic studies indicated that LIMCH1 upregulated PD-L1 via MAPK pathway activation, suppressed CD4 + and CD8 + T-cell infiltration, and led to an immunosuppressive tumor microenvironment. High LIMCH1 expression was also linked to low response rates to anti-PD-1 therapy, suggesting it may influence immunotherapy efficacy. Conclusion LIMCH1 promotes tumor activity in breast cancer by activating the MAPK pathway, upregulating PD-L1, and enhancing immune evasion. LIMCH1 may serve as a potential therapeutic target for breast cancer immunotherapy. This study provides new evidence for the role of LIMCH1 in breast cancer and offers new insights and directions for precision therapy of breast cancer.

Francesco Albanese

Alfredo Franco-Obregón, Yee Kit Tai

Transient receptor potential (TRP) channels are broadly implicated in the developmental programs of most tissues. Amongst these tissues, skeletal muscle and adipose are noteworthy for being essential in establishing systemic metabolic balance. TRP channels respond to environmental stimuli by supplying intracellular calcium that instigates enzymatic cascades of developmental consequence and often impinge on mitochondrial function and biogenesis. Critically, aminoglycoside antibiotics (AGAs) have been shown to block the capacity of TRP channels to conduct calcium entry into the cell in response to a wide range of developmental stimuli of a biophysical nature, including mechanical, electromagnetic, thermal, and chemical. Paradoxically, in vitro paradigms commonly used to understand organismal muscle and adipose development may have been led astray by the conventional use of streptomycin, an AGA, to help prevent bacterial contamination. Accordingly, streptomycin has been shown to disrupt both in vitro and in vivo myogenesis, as well as the phenotypic switch of white adipose into beige thermogenic status. In vivo, streptomycin has been shown to disrupt TRP-mediated calcium-dependent exercise adaptations of importance to systemic metabolism. Alternatively, streptomycin has also been used to curb detrimental levels of calcium leakage into dystrophic skeletal muscle through aberrantly gated TRPC1 channels that have been shown to be involved in the etiology of X-linked muscular dystrophies. TRP channels susceptible to AGA antagonism are critically involved in modulating the development of muscle and adipose tissues that, if administered to behaving animals, may translate to systemwide metabolic disruption. Regenerative medicine and clinical communities need to be made aware of this caveat of AGA usage and seek viable alternatives, to prevent contamination or infection in in vitro and in vivo paradigms, respectively.

Wanjun Liu, Si Chen, Wenqing Xie et al.

Abstract Background The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC). Methods In vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients’ overall survival (OS) was analyzed by Kaplan–Meier analysis. Results Ectopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis. Conclusions Together, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.

Fabrice Lucien, Dakota Gustafson, Metka Lenassi et al.

Abstract Blood is the most commonly used body fluid for extracellular vesicle (EV) research. The composition of a blood sample and its derivatives (i.e., plasma and serum) are not only donor‐dependent but also influenced by collection and preparation protocols. Since there are hundreds of pre‐analytical protocols and over forty variables, the development of standard operating procedures for EV research is very challenging. To improve the reproducibility of blood EV research, the International Society for Extracellular Vesicles (ISEV) Blood EV Task Force proposes standardized reporting of (i) the applied blood collection and preparation protocol and (ii) the quality of the prepared plasma and serum samples. Gathering detailed information will provide insight into the performance of the protocols and more effectively identify potential confounders in the prepared plasma and serum samples. To collect this information, the ISEV Blood EV Task Force created the Minimal Information for Blood EV research (MIBlood‐EV), a tool to record and report information about pre‐analytical protocols used for plasma and serum preparation as well as assays used to assess the quality of these preparations. This tool does not require modifications of established local pre‐analytical protocols and can be easily implemented to enhance existing databases thereby enabling evidence‐based optimization of pre‐analytical protocols through meta‐analysis. Taken together, insight into the quality of prepared plasma and serum samples will (i) improve the quality of biobanks for EV research, (ii) guide the exchange of plasma and serum samples between biobanks and laboratories, (iii) facilitate inter‐laboratory comparative EV studies, and (iv) improve the peer review process.

Ruiyao Xu, Xianxian Wang, Sadia Safi et al.

Reception of Wnt signals by cells is predominantly mediated by Frizzled receptors in conjunction with a co-receptor, the latter being LRP6 or LRP5 for the Wnt/β-catenin signalling pathway. It is important that cells maintain precise control of receptor activation events in order to properly regulate Wnt/β-catenin signalling as aberrant signalling can result in disease in humans. Phosphorylation of the intracellular domain (ICD) of LRP6 is well known to regulate Wntβ-catenin signalling; however, less is known for regulatory post-translational modification events within the extracellular domain (ECD). Using a cell culture-based expression screen for functional regulators of LRP6, we identified a glycosyltransferase, B3GnT2-like, from a teleost fish (medaka) cDNA library, that modifies LRP6 and regulates Wnt/β-catenin signalling. We provide both gain-of-function and loss-of-function evidence that the single human homolog, B3GnT2, promotes extension of polylactosamine chains at multiple <i>N</i>-glycans on LRP6, thereby enhancing trafficking of LRP6 to the plasma membrane and promoting Wnt/β-catenin signalling. Our findings further highlight the importance of LRP6 as a regulatory hub in Wnt signalling and provide one of the few examples of how a specific glycosyltransferase appears to selectively target a signalling pathway component to alter cellular signalling events.

Thatohatsi Sefuthi, Lungiswa Nkonki

Abstract Objective The aims of this systematic review were to (1) identify primary- and model-based economic evaluations of cervical cancer screening methods and to (2) provide a contextual summary of valuation outcomes associated with three types of cervical cancer screening tests: visual inspection with acetic acid, human papillomavirus deoxyribonucleic acid, and Papanicolaou smear. Introduction Cervical cancer screening is an important public health priority with the potential to improve the detection of precancerous lesions in high-risk females for early intervention and disease prevention. Test performance and cost-effectiveness differ based on the specific screening method used across different platforms. There is a need to appraise existing economic evaluations of cervical cancer screening methods. Methods This review considered primary-based and model-based full economic evaluations of cervical cancer screening methods. The evaluation methods of interest included cost-effectiveness analysis, cost-utility analysis, cost-minimization analysis, cost–benefit analysis, and cost-consequence analysis. We searched Scopus, PubMed, National Health Economic Evaluation Database (NH EED), Cochrane, and the Health Economic Evaluation Database for full economic evaluations of cancer screening methods. No formal date restrictions were applied. Model-based and primary-based full economic evaluations were included. A critical appraisal of included studies was performed by the main investigator, while a second independent reviewer assessed critical appraisal findings for any inconsistencies. Data were extracted using a standardised data extraction tool for economic evaluations. The ultimate outcomes of costs, effectiveness, benefits, and utilities of cervical cancer screening modalities were extracted from included studies, analysed, and summarised. Results From a total of 671 screened studies, 44 studies met the study inclusion criteria. Forty-three studies were cost-effectiveness analyses, one study reported both cost-utility and cost-effectiveness outcomes, and another study reported cost utilities of cervical cancer screening methods only. Human papillomavirus (HPV) DNA testing was reported as a dominant stand-alone screening test by 14 studies, while five studies reported visual inspection with acetic acid (VIA) as a dominant stand-alone screening test. Primary HPV screening strategies were dominant in 21 studies, while three studies reported cytology-based screening strategies as the dominant screening method. Conclusions Existing evidence indicates that HPV-based and VIA testing strategies are cost-effective, but this is dependent on setting. Our review suggests the limited cost-effectiveness of cytology-based testing, which may be due in part to the need for specific infrastructures and human resources. Systematic review registration PROSPERO CRD42020212454 .

Judit Vágó, Katalin Kiss, Edina Karanyicz et al.

We investigated the gene expression pattern of selected enzymes involved in DNA methylation and the effects of the DNA methylation inhibitor 5-azacytidine during in vitro and in vivo cartilage formation. Based on the data of a PCR array performed on chondrifying BMP2-overexpressing C3H10T1/2 cells, the relative expressions of <i>Tet1</i> (tet methylcytosine dioxygenase 1), <i>Dnmt3a</i> (DNA methyltransferase 3), and <i>Ogt</i> (O-linked <i>N</i>-acetylglucosamine transferase) were further examined with RT-qPCR in murine cell line-based and primary chondrifying micromass cultures. We found very strong but gradually decreasing expression of <i>Tet1</i> throughout the entire course of in vitro cartilage differentiation along with strong signals in the cartilaginous embryonic skeleton using specific RNA probes for in situ hybridization on frozen sections of 15-day-old mouse embryos. <i>Dnmt3a</i> and <i>Ogt</i> expressions did not show significant changes with RT-qPCR and gave weak in situ hybridization signals. The DNA methylation inhibitor 5-azacytidine reduced cartilage-specific gene expression and cartilage formation when applied during the early stages of chondrogenesis. In contrast, it had a stimulatory effect when added to differentiated chondrocytes, and quantitative methylation-specific PCR proved that the DNA methylation pattern of key chondrogenic marker genes was altered by the treatment. Our results indicate that the DNA demethylation inducing <i>Tet1</i> plays a significant role during chondrogenesis, and inhibition of DNA methylation exerts distinct effects in different phases of in vitro cartilage formation.

Chien-Ju Lin, Shan-Ru Jeng, Zhen-Yuan Lei et al.

The gonochoristic feature with environmental sex determination that occurs during the yellow stage in the eel provides an interesting model to investigate the mechanisms of gonadal development. We previously studied various sex-related genes during gonadal sex differentiation in Japanese eels. In the present study, the members of transforming growth factor beta (TGF-β) superfamily were investigated. Transcript levels of anti-Müllerian hormone, its receptor, gonadal soma-derived factor (<i>amh</i>, <i>amhr2</i>, and <i>gsdf</i>, respectively) measured by real-time polymerase chain reaction (qPCR) showed a strong sexual dimorphism. Transcripts were dominantly expressed in the testis, and their levels significantly increased with testicular differentiation. In contrast, the expressions of <i>amh</i>, <i>amhr2,</i> and <i>gsdf</i> transcripts were low in the ovary of E2-feminized female eels. In situ hybridization detected <i>gsdf</i> (but not <i>amh</i>) transcript signals in undifferentiated gonads. <i>amh</i> and <i>gsdf</i> signals were localized to Sertoli cells and had increased significantly with testicular differentiation. Weak <i>gsdf</i> and no <i>amh</i> signals were detected in early ovaries of E2-feminized female eels. Transcript levels of <i>amh</i> and <i>gsdf</i> (not <i>amhr2</i>) decreased during human chorionic gonadotropin (HCG)-induced spermatogenesis in males. This study suggests that <i>amh</i>, <i>amhr2,</i> and especially <i>gsdf</i> might be involved in the gene pathway regulating testicular differentiation of Japanese eels.

Jed Overmann

Alba Corell, Sandra Ferreyra Vega, Nickoleta Hoefling et al.

Abstract Background The T2-FLAIR mismatch sign is an imaging finding highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted (non-codel) gliomas (astrocytomas). In previous studies, it has shown excellent specificity but limited sensitivity for IDH-mut astrocytomas. Whether the mismatch sign is a marker of a clinically relevant subtype of IDH-mut astrocytomas is unknown. Methods We included histopathologically verified supratentorial lower-grade gliomas (LGG) WHO grade II-III retrospectively during the period 2010–2016. In the period 2017–2018, patients with suspected LGG radiologically were prospectively included, and in this cohort other diagnoses than glioma could occur. Clinical, radiological and molecular data were collected. For clinical evaluation we included all patients with IDH-mut astrocytomas. In the 2010–2016 cohort DNA methylation analysis with Infinium MethylationEPIC BeadChip (Illumina) was performed for patients with an IDH-mut astrocytoma with available tissue. We aimed to examine the association of the T2-FLAIR mismatch sign with clinical factors and outcomes. Additionally, we evaluated the diagnostic reliability of the mismatch sign and its relation to methylation profiles. Results Out of 215 patients with LGG, 135 had known IDH-mutation and 1p19q codeletion status. Fifty patients had an IDH-mut astrocytoma and 12 of these (24.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut detection were 26.4 and 97.6%, respectively. There were no differences between patients with an IDH-mut astrocytoma with or without mismatch sign when grouped according to T2-FLAIR mismatch sign with respect to baseline characteristics, clinical outcomes and methylation profiles. The overall interrater agreement between neuroradiologist and clinical neurosurgeons for the T2-FLAIR mismatch sign was significant when all 215 MRI examination assessed (κ = 0.77, p < 0.001, N = 215). Conclusion The T2-FLAIR mismatch sign in patients with an IDH-mut astrocytoma is not associated with clinical presentation or outcome. It seems unlikely that the IDH-mut astrocytomas with mismatch sign represent a specific subentity. Finally, we have validated that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.

Jean-Philippe Leduc-Gaudet, Dominique Mayaki, Olivier Reynaud et al.

Sepsis elicits skeletal muscle weakness and fiber atrophy. The accumulation of injured mitochondria and depressed mitochondrial functions are considered as important triggers of sepsis-induced muscle atrophy. It is unclear whether mitochondrial dysfunctions in septic muscles are due to the inadequate activation of quality control processes. We hypothesized that overexpressing Parkin, a protein responsible for the recycling of dysfunctional mitochondria by the autophagy pathway (mitophagy), would confer protection against sepsis-induced muscle atrophy by improving mitochondrial quality and content. Parkin was overexpressed for four weeks in the limb muscles of four-week old mice using intramuscular injections of adeno-associated viruses (AAVs). The cecal ligation and perforation (CLP) procedure was used to induce sepsis. Sham operated animals were used as controls. All animals were studied for 48 h post CLP. Sepsis resulted in major body weight loss and myofiber atrophy. Parkin overexpression prevented myofiber atrophy in CLP mice. Quantitative two-dimensional transmission electron microscopy revealed that sepsis is associated with the accumulation of enlarged and complex mitochondria, an effect which was attenuated by Parkin overexpression. Parkin overexpression also prevented a sepsis-induced decrease in the content of mitochondrial subunits of NADH dehydrogenase and cytochrome C oxidase. We conclude that Parkin overexpression prevents sepsis-induced skeletal muscle atrophy, likely by improving mitochondrial quality and contents.

Xuegang Wang, Rong Wang, Zhun Wu et al.

Abstract Background Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) is significantly down-regulated in various kinds of tumors, however, the mechanisms of action and functions of circITCH gene in prostate cancer (PC) are still under investigation. The mail goal of this research was to study the functional role of Circ-ITCH gene in prostate cancer and to illuminate the function role of circ-ITCH gene in prostate cancer by targeting miR-17-5p/HOXB13. Methods RT-qPCR was applied to measure the expression level of circ-ITCH and miR-17-5p in PC cell lines and tissues. CCK-8, colony formation, Brdu incorporation labeling and flow cytometry assays were applied to detect the effects of circ-ITCH and miR-17-5p on proliferation and cell apoptosis. Target gene prediction and screening, luciferase reporter gene assays were utilized to assess downstream target genes of miR-17-5p and Circ-ITCH. The protein and expression of HOXB13 gene were measured by Western blotting and RT-qPCR. Results CircITCH was significantly reduced in PC cell lines and tissues. Low circITCH expression level was highly related with preoperative PSA, tumor stage and Gleason score. Overexpression of circITCH can inhibit the malignant phenotype of prostate cancer. There was a high negative relationship between the expression level of microRNA-17-5p and circITCH in PC tissues, however, there existed a positive relationship between the expression of HOXB13 and circITCH. CircITCH acted as a sponge of miR-17-5p to increase HOXB13 gene expression. In addition, miR-17-5p overexpression or HOXB13 silencing can reduce the carcinogenic effects of circICCH in prostate cancer. Conclusion CircITCH promoted prostate cancer progression by regulating the HOXB13/miR-17-5p axis, and circITCH have a potential usage as therapeutic target for PC tumors.

Carrie Stoltzman, Mary Prieve, Elizabeth Dam et al.

Gabriela Oprea-Ilies, Momin T. Siddiqui

Andrew A. Walker, Mark L. Mayhew, Jiayi Jin et al.

Venom can be used both offensively for prey capture and defensively to deter predators. Here, Walker and colleagues demonstrate that the assassin bug Pristhesancus plagipennis has two distinct venom glands that produce venoms with distinct compositions that can be elicited by different stimuli.