This study compared the capacity of two different models of HIIT [high-(HC) and low-(LC) compression], with or without the use of berberine (BBR), on NOD-like receptor pyrin domain-containing protein-3 (NLRP3), H19, interleukin (IL)-1β, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance markers. Fifty-four middle-aged men with overweight or obesity and prediabetes [fasting blood glucose (FBG) 110-180 mg/dL] were randomly and equally assigned to the HC, LC, HC + BBR, LC + BBR, BBR, and non-exercising control (CON) groups. The HC (2:1 work-to-rest) and LC (1:1 work-to-rest) home-based training programs included 2-4 sets of 8 exercises at 80%-95% HRmax, twice a week for 8 weeks. Participants in the berberine groups received approximately 1000 mg daily. All exercise interventions led to a significant reduction in hs-CRP, IL-1β, insulin, FBG, and insulin resistance index (HOMA-IR) versus CON. Notably, there was a significant reduction in FBG and HOMA-IR with the BBR group compared to the baseline. Both NLRP3 and H19 experienced a significant drop only with LC in comparison to the baseline. While both exercise protocols were beneficial overall, LC uniquely exhibited more anti-inflammatory effects, as indicated by reductions in H19 and NLRP3. However, the addition of berberine to the exercise programs did not demonstrate additional benefits.

The coordinated action of VEGF, IGF1/2 and H19 factors influences the development of endometriosis. The aim of this study was to analyze the expression level of these genes in patients with endometriosis. The study group consisted of 100 patients who were diagnosed with endometriosis on laparoscopic and pathological examination. The control group consisted of 100 patients who were found to be free of endometriosis during the surgical procedure and whose eutopic endometrium wasnormal on histopathological examination. These patients were operated on for uterine fibroids. Gene expression was determined by RT-PCR. The expression of the VEGF gene was significantly higher in the samples classified as clinical stage 1-2 compared to the control material (p < 0.05). There was also a statistically significant difference between the samples studied at clinical stages 1-2 and 3-4 (p < 0.01). The expression of the VEGF gene in the group classified as 1-2 was significantly higher. IGF1 gene expression was significantly lower both in the group of samples classified as clinical stages 1-2 and 3-4 compared to the control group (p < 0.05 in both cases). The expression of the H19 gene was significantly lower in the group of samples classified as clinical stage 3-4 compared to the control group (p < 0.01). The reported studies suggest significant roles of VEGF, IGF and H19 expression in the pathogenesis of endometriosis.

The Notch pathway is a key cancer driver and is important in tumor progression. Early research suggested that Notch activity was highly dependent on the expression of the intracellular cleaved domain of Notch-1 (NICD). However, recent insights into Notch signaling reveal the presence of Notch pathway signatures, which may vary depending on different cancer types and tumor microenvironments. Herein, we perform a comprehensive investigation of the Notch signaling pathway in adult T-cell leukemia (ATL) primary patient samples. Using gene arrays, we demonstrate that the Notch pathway is constitutively activated in ATL patient samples. Furthermore, the activation of Notch in ATL cells remains elevated irrespective of the presence of activating mutations in Notch itself or its repressor, FBXW7, and that ATL cells are dependent upon Notch-1 expression for proliferation and survival. We demonstrate that ATL cells exhibit the expression of pivotal Notch-related genes, including notch-1, hes1, c-myc, H19, and hes4, thereby defining a critical Notch signature associated with ATL disease. Finally, we demonstrate that lncRNA H19 is highly expressed in ATL patient samples and ATL cells and contributes to Notch signaling activation. Collectively, our results shed further light on the Notch pathway in ATL leukemia and reveal new therapeutic approaches to inhibit Notch activation in ATL cells.

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients\' blood.

H19 is an essential imprinted gene that is expressed to govern normal embryonic development. During reprogramming, the parental pronuclei have asymmetric reprogramming capacities and the critical reprogramming factors predominantly reside in the male pronucleus. After inhibiting the expression of H19 and Gtl2, androgenetic haploid ESCs (AG-haESCs) can efficiently and stably support the generation of healthy SC pups at a rate of ~20%, and double-knockout parthenogenetic haESCs can also produce efficiently. Induced pluripotent stem (iPS) cell reprogramming is thought to have a characteristic epigenetic pattern that is the reverse of its developmental potential; however, it is unclear how H19 participates in iPS cell reprogramming. Here, we showed that the expression of H19 was transiently increased during iPSC reprogramming. H19 knockdown resulted in greater reprogramming efficiency. The genes associated with pluripotency showed enhanced expression during the early reprogramming process, and the Oct4 promoter was demethylated by bisulfite genomic sequencing analysis. Moreover, expression analysis revealed that the mesenchymal master regulators associated with epithelial-to-mesenchymal transition (EMT) were downregulated during reprogramming in H19 knockdown. These findings provide functional insight into the role of H19 as a barrier to the early reprogramming process.

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer in women. Treatment approaches that differ between estrogen-positive (ER+) and triple-negative BC cells (TNBCs) and may subsequently affect cancer biomarkers, such as H19 and telomerase, are an emanating delight in BC research. For instance, all-trans-Retinoic acid (ATRA) could represent a potent regulator of these oncogenes, regulating microRNAs, mostly let-7a microRNA (miR-let-7a), which targets the glycolysis pathway, mainly pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) enzymes. Here, we investigated the potential role of ATRA in H19, telomerase, miR-let-7a, and glycolytic enzymes modulation in ER + and TNBC cells.
METHODS: MCF-7 and MDA-MB-231 cells were treated with 5 µM ATRA and/or 100 nM fulvestrant. Then, ATRA-treated or control MCF-7 cells were transfected with either H19 or hTERT siRNA. Afterward, ATRA-treated or untreated MDA-MB-231 cells were transfected with estrogen receptor alpha ER(α) or beta ER(β) expression plasmids. RNA expression was evaluated by RT‒qPCR, and proteins were assessed by Western blot. PKM2 activity was measured using an NADH/LDH coupled enzymatic assay, and telomerase activity was evaluated with a quantitative telomeric repeat amplification protocol assay. Student\'s t-test or one-way ANOVA was used to analyze data from replicates.
RESULTS: Our results showed that MCF-7 cells were more responsive to ATRA than MDA-MB-231 cells. In MCF-7 cells, ATRA and/or fulvestrant decreased ER(α), H19, telomerase, PKM2, and LDHA, whereas ER(β) and miR-let-7a increased. H19 or hTERT knockdown with or without ATRA treatment showed similar results to those obtained after ATRA treatment, and a potential interconnection between H19 and hTERT was found. However, in MDA-MB-231 cells, RNA expression of the aforementioned genes was modulated after ATRA and/or fulvestrant, with no significant effect on protein and activity levels. Overexpression of ER(α) or ER(β) in MDA-MB-231 cells induced telomerase activity, PKM2 and LDHA expression, in which ATRA treatment combined with plasmid transfection decreased glycolytic enzyme expression.
CONCLUSIONS: To the best of our knowledge, our study is the first to elucidate a new potential interaction between the estrogen receptor and glycolytic enzymes in ER + BC cells through miR-let-7a.

Hypoxic preconditioning has been recognized as a promotive factor for accelerating cutaneous wound healing. Our previous study uncovered that exosomal lncRNA H19, derived from adipose-derived stem cells (ADSCs), plays a crucial role in orchestrating cutaneous wound healing. Herein, we aimed to explore whether there is a connection between hypoxia and ADSC-derived exosomes (ADSCs-exos) in cutaneous wound healing. Exosomes extracted from ADSCs under normoxic and hypoxic conditions were identified using transmission electron microscope (TEM) and particle size analysis. The effects of ADSCs-exos on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8, EdU, wound healing, and tube formation assays. Expression patterns of H19, HIF-1α, and USP22 were measured. Co-immunoprecipitation, chromatin immunoprecipitation, ubiquitination, and luciferase reporter assays were conducted to confirm the USP22/HIF-1α/H19 axis, which was further validated in a mice model of skin wound. Exosomes extracted from hypoxia-treated ADSCs (termed as H-ADSCs-exos) significantly increased cell proliferation, migration, and angiogenesis in H2O2-exposed HUVECs, and promoted cutaneous wound healing in vivo. Moreover, H-ADSCs and H-ADSCs-exos, which exhibited higher levels of H19, were found to be transcriptionally activated by HIF-1α. Mechanically, H-ADSCs carrying USP22 accounted for deubiquitinating and stabilizing HIF-1α. Additionally, H-ADSCs-exos improved cell proliferation, migration, and angiogenesis in H2O2-triggered HUVECs by activating USP22/HIF-1α axis and promoting H19 expression, which may provide a new clue for the clinical treatment of cutaneous wound healing.

OBJECTIVE: This study aimed to investigate the expression of H19 and its possible molecular mechanism in systemic lupus erythematosus (SLE).
METHODS: The expression of H19 and miR-19b in serum and peripheral blood mononuclear cells (PBMCs) were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Receiver operator characteristic (ROC) curve was constructed to evaluate the diagnostic value of serum H19 in SLE. Pearson correlation coefficient was used to analyze the correlation between serum levels of H19 and miR-19b. Flow cytometry and Cell counting kit-8 (CCK-8) assay were performed to detect cell apoptosis and viability. The levels of pro-inflammatory and anti-inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene assay was conducted to verify the interaction between H19 and miR-19b.
RESULTS: The expression of H19 and miR-19b in SLE group were up-regulated and down-regulated, respectively. Serum H19 has certain clinical diagnostic value in SLE. In in vitro studies, overexpression of H19 can significantly inhibit the viability of PBMCs and promote apoptosis and inflammatory response of PBMCs by interacting with miR-19b.
CONCLUSIONS: The expression of H19 is upregulated in patients with SLE and plays a role in cell function and inflammation by targeting miR-19b in PBMCs, which may be one of the pathological mechanisms of SLE.

Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD-1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944-5p, miR-105-5p, miR-486-5p, miR-506-5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs-CCAT-1, MALAT-1, or H19-markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of co-cultured primary immune cells. On the immune side, ectopic expression of the under-expressed microRNAs; miR-486-5p, miR-506-5p, and miR-30a-5p significantly decreased the transcript levels of PD-1 in PBMCs with no effect on TIGIT. On the other hand, ectopic expression of miR-944-5p and miR-105-5p in PBMCs dramatically reduced the co-expression of PD-1 and TIGIT. Finally, all studied miRNAs enhanced the cytotoxic effects of PBMCs against Huh7 cells. However, miR-105-5p showed the highest augmentation for PBMCs cytotoxicity against HCC cells. In conclusion, this study highlights a novel co-targeting strategy using miR-105-5p mimics, MALAT-1, CCAT-1 and H19 siRNAs to efficiently hampers the immune checkpoints; PD-L1/PD-1 and CD155/TIGIT immune evasion properties in HCC.

Oral squamous cell carcinoma (OSCC) showed a seemingly increasing incidence in the last decade. In India, despite the use of tobacco decreased rapidly, in the past five years, the incidence pattern of OSCC over gender and age showed a drastic shift. About 51 % of the head and neck cancers are not associated with habits. Studies exploring various contributing factors in the incidence of this malignancy have documented. Recently, the epigenetic factors associated with the induction and progression of OSCC were explored. More than 90 % of the human genome is made up of non-coding transcriptome, which believed to be noises. However, these non-coding RNAs were identified to be the major epigenetic modulators, which raises concern over incidence of carcinoma in non-habit patients. H19 is a long non coding RNA which proved to be an effective biomarker in various carcinoma. Its role in oral squamous cell cancer was not investigated in depth. This review discusses in detail the various epigenetic role of H19 in inducing oral carcinogenesis.