Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.

We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35-762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.

Establishment of New Genetic Markers and Methods for Sex Determination of Mouse and Human Cells using Polymerase Chain Reactions and Crude DNA Samples.

The currently available methods for sexing human or mouse cells have weaknesses. Therefore, it is necessary to establish new methods. We used bioinformatics approach to identify genes that have alleles on both the X and Y chromosomes of mouse and human genomes and have a region showing a significant difference between the X and Y alleles.

RNA expression profiling from the liquid fraction of synovial fluid in knee joint osteoarthritis patients.

Objective: To investigate the RNA profile of synovial fluid (SF) from osteoarthritis (OA) patients and carry out cluster analysis of OA-related genes.

Methods: RNA of SF from OA patients was isolated using RNA-specific Trizol. A cDNA library was built and subjected to the second-generation sequencing using HisSeq4000 with a data size of 8G.

Mutation or not, what directly establishes a neoplastic state, namely cellular immortality and autonomy, still remains unknown and should be prioritized in our research.

Although the concept that cancer is caused by mutations has been widely accepted, there still are ample data deprecating it. For example, embryonic cells displaced in non-embryonic environments may develop to cancer, whereas cancer cells placed in embryonic environments may be reverted to phenotypic normal. Although many intracellular or extracellular aberrations are known to be able to initiate a lengthy tumorigenesis, the molecular or cellular alterations that directly establish a neoplastic state, namely cellular immortality and autonomy, still remain unknown.

ACTB and GAPDH appear at multiple SDS-PAGE positions, thus not suitable as reference genes for determining protein loading in techniques like Western blotting.

We performed polyacrylamide gel electrophoresis of human proteins with sodium dodecyl sulfate, isolated proteins at multiple positions, and then used liquid chromatography and tandem mass spectrometry (LC-MS/MS) to determine the protein identities. Although beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are 41.7 and 36 kDa proteins, respectively, LC-MS/MS identified their peptides at all the positions studied.

SNHG16 lncRNAs are overexpressed and may be oncogenic in human gastric cancer by regulating cell cycle progression.

The small nucleolar RNA host gene 16 (SNHG16) has recently been shown to be a putative oncogene in gastric cancer (GC) and other cancer types, but how its four lncRNA variants are expressed in any physiological and pathological situation remains unknown. To investigate the expression and function of the four lncRNA variants of SNHG16, mainly the variant 1, in GC, we performed quantitative PCR to determine the RNA levels of the four variants in 60 GC tissue samples and several cell lines. We also studied how knocking down of SNHG16 with siRNA affected proliferation, apoptosis, cell cycle progression, as well as migration and invasion of GC cells.

At elevated temperatures, heat shock protein genes show altered ratios of different RNAs and expression of new RNAs, including several novel HSPB1 mRNAs encoding HSP27 protein isoforms.

Heat shock proteins (HSP) serve as chaperones to maintain the physiological conformation and function of numerous cellular proteins when the ambient temperature is increased. To determine how accurate the general assumption that HSP gene expression is increased in febrile situations is, the RNA levels of the HSF1 (heat shock transcription factor 1) gene and certain HSP genes were determined in three cell lines cultured at 37˚C or 39˚C for three days. At 39˚C, the expression of HSF1, HSPB1, HSP90AA1 and HSP70A1L genes demonstrated complex changes in the ratios of expression levels between different RNA variants of the same gene.

Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats.

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls.

Ribosomal S6 protein kinase 4 promotes radioresistance in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC.

Evidence for immortality and autonomy in animal cancer models is often not provided, which causes confusion on key issues of cancer biology.

Modern research into carcinogenesis has undergone three phases. Surgeons and pathologists started the first phase roughly 250 years ago, establishing morphological traits of tumors for pathologic diagnosis, and setting immortality and autonomy as indispensable criteria for neoplasms. A century ago, medical doctors, biologists and chemists started to enhance "experimental cancer research" by establishing many animal models of chemical-induced carcinogenesis for studies of cellular mechanisms.

About three-fourths of mouse proteins unexpectedly appear at a low position of SDS-PAGE, often as additional isoforms, questioning whether all protein isoforms have been eliminated in gene-knockout cells or organisms.

Most genes in evolutionarily complex genomes are expressed to multiple protein isoforms, but there is not yet any simple high-throughput approach to identify these isoforms. Using an oversimplified top-down LC-MS/MS strategy, we detected, around the 26-kD position of SDS-PAGE, proteins produced from 782 genes in a Cdk4-/- mouse embryonic fibroblast cell line. Interestingly, only 213 (27.

Spontaneous Cancers, But Not Many Induced Ones in Animals, Resemble Semi-New Organisms that Possess a Unique Programmed Cell Death Mode Different from Apoptosis, Senescent Death, Necrosis and Stress-Induced Cell Death.

There are four basic cell death modes in animals, i.e. physiological senescent death (SD) and apoptosis as well as pathological necrosis and stress-induced cell death (SICD).

Evaluating the Remote Control of Programmed Cell Death, with or without a Compensatory Cell Proliferation.

Organisms and their different component levels, whether organelle, cellular or other, come by birth and go by death, and the deaths are often balanced by new births. Evolution on the one hand has built demise program(s) in cells of organisms but on the other hand has established external controls on the program(s). For instance, evolution has established death program(s) in animal cells so that the cells can, when it is needed, commit apoptosis or senescent death (SD) in physiological situations and stress-induced cell death (SICD) in pathological situations.

Knockdown of long noncoding RNA GHET1 inhibits cell‑cycle progression and invasion of gastric cancer cells.

GHET1 is an oncogenic long noncoding RNA (lncRNA) that promotes the proliferation and invasion of many malignant cell types. However, the function and underlying mechanisms of lncRNA GHET1 in gastric cancer are not fully understood. In this study, the expression of GHET1 was investigated in gastric cancer and it was determined whether GHET1 may potentially be used as a biomarker for the disease.

While it is not deliberate, much of today's biomedical research contains logical and technical flaws, showing a need for corrective action.

Biomedical research has advanced swiftly in recent decades, largely due to progress in biotechnology. However, this rapid spread of new, and not always-fully understood, technology has also created a lot of false or irreproducible data and artifacts, which sometimes have led to erroneous conclusions. When describing various scientific issues, scientists have developed a habit of saying "on one hand… but on the other hand…", because discrepant data and conclusions have become omnipresent.

Management and survival analysis of elderly patients with a cancer in the digestive system who refused to receive anticancer treatments.

Treatment and management of cancers in elderly patients require some special considerations. A better understanding of how cancers progress in those elderly patients who have not received any anticancer treatments could better help us in treating these patients and in making end-of-life decisions. Over the past years, we had encountered 57 elderly patients, aged 75 to 94 years (87.

Transcriptional-Readthrough RNAs Reflect the Phenomenon of "A Gene Contains Gene(s)" or "Gene(s) within a Gene" in the Human Genome, and Thus Are Not Chimeric RNAs.

Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have been identified in human cells.

The well-accepted notion that gene amplification contributes to increased expression still remains, after all these years, a reasonable but unproven assumption.

"Gene amplification causes overexpression" is a longstanding and well-accepted concept in cancer genetics. However, raking the whole literature, we find only statistical analyses showing a positive correlation between gene copy number and expression level, but do not find convincing experimental corroboration for this notion, for most of the amplified oncogenes in cancers. Since an association does not need to be an actual causal relation, in our opinion, this widespread notion still remains a reasonable but unproven assumption awaiting experimental verification.

Genetic diversity of Guangxi chicken breeds assessed with microsatellites and the mitochondrial DNA D-loop region.

The domestic chicken (Gallus gallus domesticus) is an excellent model for genetic studies of phenotypic diversity. The Guangxi Region of China possesses several native chicken breeds displaying a broad range of phenotypes well adapted to the extreme hot-and-wet environments in the region. We thus evaluated the genetic diversity and relationships among six native chicken populations of the Guangxi region and also evaluated two commercial breeds (Arbor Acres and Roman chickens).

To Know How a Gene Works, We Need to Redefine It First but then, More Importantly, to Let the Cell Itself Decide How to Transcribe and Process Its RNAs.

Recent genomic and ribonomic research reveals that our genome produces a stupendous amount of non-coding RNAs (ncRNAs), including antisense RNAs, and that many genes contain other gene(s) in their introns. Since ncRNAs either regulate the transcription, translation or stability of mRNAs or directly exert cellular functions, they should be regarded as the fourth category of RNAs, after ribosomal, messenger and transfer RNAs. These and other research advances challenge the current concept of gene and raise a question as to how we should redefine gene.

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.

Background: Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR.

Therapeutic intervention of experimental breast cancer bone metastasis by indole-3-carbinol in SCID-human mouse model.

Several lines of experimental evidence have suggested that chemokine receptor CXCR4, a metastasis-promoting molecule, may play important roles in breast cancer bone metastasis. There is emerging evidence linking CXCR4 to matrix metalloproteinases (MMP) as well as their regulator nuclear factor-kappaB (NF-kappaB), a key transcription factor, which is known to activate metastasis-promoting molecules for many types of malignancies, including breast cancer. A recent study also showed that promoter region of CXCR4 has several NF-kappaB-binding sites, suggesting that there may be a cross-talk between CXCR4 and NF-kappaB.

Characterization of pancreatic lesions from MT-tgf alpha, Ela-myc and MT-tgf alpha/Ela-myc single and double transgenic mice.

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgf alpha mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgf alpha-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males.

Synergistic effects of androgen and estrogen on the mouse uterus and mammary gland.

Many studies have suggested that elevated estrogens and androgens may be etiologically related to the development of breast cancer, endometrial cancer and uterine leiomyomas. We and other investigators have previously shown that estrogen and androgen are synergistic in the induction of mammary carcinogenesis in the Noble rat. However, the mechanisms behind the synergy is unknown, and it is unclear whether such synergy is unique for the Noble rat and for the mammary gland.

Cell death in MMTV-c-myc transgenic mouse mammary tumors may not be typical apoptosis.

Enforced expression of c-myc has been shown to serve as an apoptotic stimulus in cultured cells. Prior studies have also demonstrated that several tissues expressing c-myc transgene display a large number of dead cells, although a morphologic or biochemical verification of apoptosis in these tissues has actually not been presented. In the present study, we examined the morphologic properties of cell death in the mammary tumors developed from MMTV-c-myc transgenic mice.