Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) include polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. Unlike monogenic disorders, a more complicated series of genetic mutations are believed to be responsible for MPN with various degrees of thromboembolic and bleeding complications. Thrombosis is one of the early manifestations in patients with MPN. To date

As a BET bromodomain inhibitor, JQ1 has been proven have efficacy against a number of different cancers. In terms of male reproduction, JQ1 may be used as a new type of contraceptive, since JQ1 treatment in male mice could lead to germ cell defects and a decrease of sperm motility, moreover, this effect is reversible. However, the mechanism of JQ1 acting on gene regulation in spermatogenesis remains

Background The regulation of β-cell mass in the status of nondiabetic obesity remains not well understood. We aimed to investigate the role of circulating exosome-like vesicles (ELVs) isolated from humans with simple obesity in the regulation of islet β-cell mass. Methods Between June 2017 and July 2019, 81 subjects with simple obesity and 102 healthy volunteers with normal weight were recruited. ELVs

The programmed cell death 10 (PDCD10) gene was originally identified as an apoptosis-related gene, although it is now usually known as CCM3, as the third causative gene of cerebral cavernous malformation (CCM). CCM is a neurovascular disease that is characterized by vascular malformations and is associated with headaches, seizures, focal neurological deficits, and cerebral hemorrhage. The PDCD10/CCM3

Intervertebral disc degeneration is the main contributor to low back pain, now the leading cause of disability worldwide. Gene transfer, either in a therapeutic attempt or in basic research to understand the mechanisms of disc degeneration, is a fascinating and promising tool to manipulate the complex physiology of the disc. Viral vectors based on the adeno‐associated virus (AAV) have emerged as powerful

The pandemic of COVID-19 caused by SARS-CoV-2 has made serious threats to the public health. Antibodies have been considered as promising therapeutics for the prevention and treatment of pathogens. So far, effectors that can influence the sustainability of SARS-CoV-2 specific antibodies in COVID-19 patients are still unclear. In this paper, we attempted to find potential key factors correlated with

Although it is widely accepted that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are readily available, robustly reproducible, and physiologically appropriate human cells for clinical applications and research in the cardiovascular field, hiPSC-CMs cultured in vitro retain an immature metabolic phenotype that limits their application, and little is known about the underlying

Metastasis is a major challenge in the treatment of cancer. Exosomes are a class of small extracellular vesicles (EVs) that play critical roles in several human diseases, especially cancer, by transferring information (e.g. DNA, RNA, and protein) via cell-to-cell communication. Numerous recent studies have shown that exosomal long non-coding RNAs (lncRNAs) play crucial regulatory roles in cancer metastasis

Osteoporosis, fracture, large-scale craniofacial defects and osteonecrosis are hot topics and are still underdiagnosed and undertreated in the clinic. It is urgent to understand the molecular mechanisms corresponding to the regulation of bone formation. CMTM3 (CKLF-like MARVEL transmembrane domain containing 3) connects the classic chemokine to the transmembrane 4 superfamily and plays an important

This review provides an updated account on the current methods, principles and mechanism of action of therapies for the detection of molecular markers of therapeutic importance in the prognosis of breast cancer progression and recurrence, which includes estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER2). Indeed, hormone-receptors namely, ER, PR, proto-oncogene

We assessed Stathmin as an immunohistochemical (IHC) indicator of phosphatidylinositol 3-kinase (PI3K) pathway activity in HPV-negative head & neck squamous cell carcinoma (HNSCC). We compared Stathmin IHC to expression of other pathway components. We also evaluated the relationship between Stathmin IHC and the mutational status of four key pathway genes. Finally, we ascertained whether Stathmin IHC

The integral membrane, Kunitz-type serine protease inhibitors HAI-1 and HAI-2 can suppress the proteolytic activity of the type 2 transmembrane serine protease matriptase with high specificity and potency. High levels of extracellular matriptase proteolytic activity have, however, been observed in some neoplastic B-cells with high levels of endogenous HAI-2, indicating that HAI-2 may be an ineffective

Ocular cells like, retinal pigment epithelium (RPE) is a highly specialized pigmented monolayer of post-mitotic cells, which is located in the posterior segment of the eye between neuro sensory retina and vascular choroid. It functions as a selective barrier and nourishes retinal visual cells. As a result of high-level oxygen consumption of retinal cells, RPE cells are vulnerable to chronic oxidative

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patients show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor

The microRNAs (miRNAs) play an important role in regulating myogenesis by targeing mRNA. However, the understanding of miRNAs in skeletal muscle development and diseases is unclear. In this study, we firstly performed the transcriptome profiling in differentiating C2C12 myoblast cells (at 0 and 4 days, named D0 and D4). Totally, we identified 187 miRNAs and 4,260 mRNAs significantly differentially

The frequency of human suffering from cancer is increasing annually across the globe. This has fueled numerous investigations aimed at the prevention and cure of various cancers. Long non-coding RNA (lncRNA) are known to play a crucial role in cancer. For instance, cancer susceptibility candidate 11 (CASC11), as one of the long non-coding RNAs, has been reported to be overexpressed in various tumors

Background Recent studies suggest that Hypocretin (HCRT, Orexin) are involved in stress regulation of depression through the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanism by which Hypocretin regulate neurobiological responses is unknown. Herein, the effects of chronic stress on the epigenetic modification of HCRT and its association with depression were explored with regard

The tumor microenvironment (TME)is heterogeneous and contains a multiple cell population with surrounded immune cells, which plays a major role in regulating metastasis. The multifunctional pathways, Hedgehog (Hh), Wnt, Notch, and NF-kB, cross-regulates metastasis in breast cancer. This review presents substantial evidence for cross-regulation of TME components and signaling pathways, which makes breast

Among the gynecological cancers, ovarian cancer is the most lethal. Its therapeutic options include a combination of chemotherapy with platinum-based compounds and cytoreductive surgery. Most ovarian cancer patients exhibit an initial response to platinum-based therapy, however, platinum resistance has led to up to 80% of this responsive cohort becoming refractory. Ovarian cancer recurrence and drug

Hepatocellular carcinoma (HCC) is among the most aggressive and lethal diseases with poor prognosis, worldwide. However, the mechanisms underlying HCC have not been comprehensively elucidated. With the recent application of high-throughput sequencing techniques, a diverse catalogue of differentially expressed long non-coding RNAs (lncRNA) in cancer have been shown to participate in HCC. Rather than

While periodontal (PD) disease is among principal causes of tooth loss worldwide, regulation of concomitant soft and mineralized PD tissues, and PD pathogenesis have not been completely clarified yet. Besides, relevant pre-clinical models and in vitro platforms have limitations in simulating human physiology. Here, we have harnessed three-dimensional bioprinting (3DBP) technology for developing a multi-cellular

DLC1 is a focal adhesion molecule that regulates cell polarity, proliferation, migration, and survival. DLC1 functions as a tumor suppressor and its expression is often down-regulated in various malignant neoplasms of epithelial origin. Recent studies have suggested that lack of DLC1 in endothelial cells may contribute to the development of angiosarcoma, and that DLC1 mutations have been identified

Cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11; also known as xCT) plays a key role in antioxidant defense by mediating cystine uptake, promoting glutathione synthesis, and maintaining cell survival under oxidative stress conditions. Recent studies showed that, to prevent toxic buildup of highly insoluble cystine inside cells, cancer cells with high expression of SLC7A11 (SLC7A11high)

Sulfuretin is a flavonoid that protects cell from damage induced by reactive oxygen species and inflammation. In this study, we investigated the role of sulfuretin in the processing of amyloid precursor protein (APP), in association with the two catalytic enzymes the α-secretase a disintegrin and metalloproteinase (ADAM10), and the beta-site APP cleaving enzyme 1 (BACE1) that play important roles in

Osteosarcoma is the most common malignant bone tumour, and the metastasis of osteosarcoma is an important cause of death. Evidence has shown that the mevalonate pathway is highly activated and is expected to be a new target for tumour therapy. In this study, we investigated the effect of mevalonate signalling on osteosarcoma metastasis and its molecular mechanism. First, we found that the key rate-limiting

The deltex family protein DTX3 is believed to possess E3 ubiquitin ligase activity, as it contains a classic RING finger domain. However, its biological role and the underlying mechanism in cancer remain largely elusive. Here, we identified DTX3 as a novel mutant p53-interacting protein in ovarian carcinoma. Mechanistically, DTX3 mediated mutant p53 ubiquitination and stabilization by perturbing the

To date, it remains unclear if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection exacerbates liver injury in patients with chronic hepatitis B virus (HBV) infection. In this study, we present a retrospective study of 133 hospitalized confirmed mild coronavirus disease 2019 (COVID-19) cases, including 116 patients with COVID-19 with negative serum hepatitis B antigen and 17 HBV

Sulindac has shown significant clinical benefit in preventing colorectal cancer progression, but its mechanism of action has not been fully elucidated. We have found that sulindac sulfide (SS) is able to inhibit cell cycle progression, particularly via G1-arrest, in human colorectal cancer cells. To understand the underlying mechanisms involved in the inhibitory activity of sulindac, we have demonstrated

Liver is an important organ for regulating glucose and lipid metabolism. Recent studies have shown that bone morphogenetic proteins (BMPs) may play important roles in regulating glucose and lipid metabolism. In our previous studies, we demonstrated that BMP4 significantly inhibits hepatic steatosis and lowers serum triglycerides, playing a protective role against the progression of non-alcoholic fatty

This study investigated the role of N6-methyladenosine RNA methylation in liver regeneration following partial hepatectomy in mice. We created a liver-specific knockout mouse model by the deletion of Mettl3, a key component of the N6-methyladenosine methyltransferase complex, using the albumin-Cre system. Mettl3 liver-specific knockout mice and their wild-type littermates were subjected to 2/3 partial

The development of premature coronary artery disease (PCAD) is dependent on both genetic predisposition and traditional risk factors. Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies. Genome-wide association studies (GWASs) have identified a considerable number of common genetic variants that are associated with PCAD. Most of these genetic variants

The retinoblastoma gene product (pRb) is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation. We found that twelve weeks after transfection of the exogenous active (ΔB/X and Δр34) or inactive (ΔS/N) forms of pRb into the 10T1/2 mesenchymal stem cells and clonal selection not a single cell line did contain exogenous pRb, despite

Mesenchymal stem cells (MSCs), multipotent stromal cells, have attracted extensive attention in the field of regenerative medicine and cell therapy due to the capacity of self-renewal, multilineage differentiation, and immune regulation. MSCs have different cellular effects in different diseases, and even have markedly different curative effects with different tissue sources, indicating the plasticity

Metastasis, is a development of secondary tumor growths at a distance from the primary site, and closely related to poor prognosis and mortality. However, there is still no effective treatment for metastatic cancer. Therefore, there is an urgent need to find an effective therapy for cancer metastasis. Plenty of evidence indicates that miR-9 can function as a promoter or suppressor in cancer metastasis

Ubiquitin-specific protease (USP7), also known as Herpesvirus-associated ubiquitin-specific protease (HAUSP), is a deubiquitinase. There has been significant recent attention on USP7 following the discovery that USP7 is a key regulator of the p53-MDM2 pathway. The USP7 protein is 130 kDa in size and has multiple domains which bind to a diverse set of proteins. These interactions mediate key developmental

SATB2 (special AT-rich sequence-binding protein 2) is a member of the special AT-rich binding protein family. As a transcription regulator, SATB2 mainly integrates higher-order chromatin organization. SATB2 expression appears to be tissue- and stage-specific, and is governed by several cellular signaling molecules and mediators. Expressed in branchial arches and osteoblast-lineage cells, SATB2 plays

Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies, including bladder cancer. This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment. Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of inflammatory molecules and signals. Recently, it has

Accumulating evidence from both animal and human studies suggests that activation of beige fat increases cellular energy expenditure, ultimately reducing adiposity. Here, we report the central role of adipocyte-derived lysyl oxidase (Lox) in the formation of thermogenic beige fat. Mice exposed to cold or a β3 agonist showed drastically lower Lox expression in thermogenically activated beige fat. Importantly

MiR-4295, located on chromosome 10q25.2, is a unique miRNA with a wide range of biological functions. miR-4295 is widely expressed in vivo, participating in the biological processes of multiple cancers. Although miR-4295 is dysregulated in various cancers, it has also been found to have the function of inhibiting cancer. At the same time, the expression of miR-4295 is related to prognosis and can be

PIWI-interacting RNA (piRNAs), once thought to be mainly functioning in germlines, are now known to play an essential role in somatic and cancerous tissues. Ping-pong cycle initiation and mitochondria-based phased production constitute the core of the piRNA biogenesis and these two processes are well conserved in mammals, including humans. By being involved in DNA methylation, histone marker deposition

Human idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis with perturbed calcium metabolism with increased bone resorption and decreased renal calcium reabsorption, which can be phenotype-copied in the genetic hypercalciuric stone-forming (GHS) rat model. Vitamin D receptor (VDR) is a nuclear receptor and plays important roles in regulating calcium homeostasis

Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death, glutathione peroxidase 4

A substantial number of male infertility is caused by azoospermia. However, the underlying etiology and the molecular basis remain largely unknown. Through single-cell (sc)RNA sequencing, we had analyzed testis biopsy samples from two patients with obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). We found only somatic cells in the NOA samples and explored the transcriptional changes

The CRISPR/Cas9 system, originally derived from the prokaryotic innate immune system, has been developed as efficient genome editing tools. It enables precise gene manipulation on chromosomal DNA through the specific binding of programmable sgRNA to target DNA, and the Cas9 protein, which has endonuclease activity, will cut a double strand break at specific locus. However, Cas9 is a foreign protein

The novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged and is responsible for the Coronavirus Disease 20191 global pandemic. Coronaviruses, including SARS-CoV-2, are strongly associated with respiratory symptoms during infection, but gastrointestinal symptoms, such as diarrhea, vomiting, nausea, and abdominal pain, have been identified in subsets of COVID-19

The BRCA1-PALB2-BRCA2 axis, or the BRCA pathway, plays key roles in genome stability maintenance and suppression of breast and several other cancers. Due to frequent p53 mutations in human BRCA1 breast cancers and mouse mammary tumors from Brca1, Brca2 and Palb2 conditional knockout models, it is often thought that p53 inactivation accelerates BRCA1/2 and PALB2-associated tumorigenesis. Here, we studied

Background SIRT6 belongs to class III sirtuin family with NAD+ -dependent histone deacetylase activities and controls multiple processes including aging, metabolism and inflammation. In recent years, increasing studies showed tumor suppressor role of SIRT6 in HCC development. Methods We established a two-stage DEN followed CCl4 induced liver carcinogenesis in the hepatic-specific SIRT6 HKO mice models

Mitochondrial autophagy (mitophagy) is the selective clearance of damaged or incomplete mitochondria by autophagy, which is critical for the functional integrity of the entire mitochondrial network and cell survival. Because dysfunction of mitophagy is closely related to many diseases, it is important to study the specific molecular mechanism and pathophysiological significance of mitophagy. FUN14

Gastric cancer (GC) is one of the most common malignancies, with an ever-increasing incidence and high mortality rate. Chromobox4 (CBX4), also named hPC2, is a small ubiquitin-related modifier (SUMO) E3 ligase. Previous studies have found that high CBX4 expression is associated with tumor size, pathologic differentiation and decreased patient survival in hepatocellular carcinoma (HCC). However, the

Obesity-induced inflammation, characterized by augmented infiltration and altered balance of macrophages, is a critical component of systemic insulin resistance. Chemokine-chemokine receptor system plays a vital role in the macrophages accumulation. CC-Chemokine Receptor-like 2(Ccrl2) is one of the receptors of Chemerin, which is a member of atypical chemokine receptors (ACKR) family, reported taking

Excessive oxidative stress is a major causative factor of endothelial dysfunction in hypertension. As an endogenous pro-oxidant, thioredoxin-interacting protein (TXNIP) contributes to oxidative damage in various tissues. The present study aimed to investigate the role of TXNIP in endothelial dysfunction in hypertensive rats. In vivo, an experimental model of acquired hypertension was established with

The important role of lncRNAs and miRNAs in directing immune responses has become increasingly clear. Recent evidence conforms that miRNAs and lncRNAs are involved in NK cell biology and diseases through RNA-protein, RNA-RNA, or RNA-DNA interactions. In this view, we summarize the contribution of miRNAs and lncRNAs to NK cell lineage development, activation and function, highlight the biological significance

Protein tyrosine phosphatase non-receptor type 18 (PTPN18) is often highly expressed in colorectal cancer (CRC), but its role in this disease remains unclear. We demonstrated that PTPN18 overexpression promotes growth and tumorigenesis in CRC cells and that PTPN18 deficiency yields the opposite results in vitro. Moreover, a xenograft assay showed that PTPN18 deficiency significantly inhibited tumorigenesis

Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma (ESCC) have shown promising results. However, a comprehensive understanding of B7-CD28 family members in ESCC is still limited. This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC. We collected 179 cases from our previously

Cellular senescence is closely associated with age-related diseases. Ovarian aging, a special type of organ senescence, is the pathophysiological foundation of the diseases of the reproductive system. It is characterized by the loss of integrity of the surface epithelium and a gradual decrease in the number of human ovarian surface epithelial cells (HOSEpiCs). To contribute to the research on delaying

The microbiota plays essential roles in health and disease, in both the intestine and the extra-intestine. Dysbiosis of the gut microbiota causes dysfunction in the intestine, which leads to inflammatory, immune and infectious diseases. Dysbiosis is also associated with diseases beyond the intestine via microbial translocation or metabolisms. The in situ breast microbiome, which may be sourced from

A decrease in energy metabolism is associated with Alzheimer’s disease (AD), but it is not known whether the observed decrease exacerbates or protects against the disease. The importance of energy metabolism in AD is reinforced by the observation that variants of dihydrolipoamide dehydrogenase (DLD), which is a subunit of both complexes, is genetically linked to late-onset AD. To determine whether