The regulatory mechanisms of cerium oxide nanoparticles in oxidative stress and emerging applications in refractory wound care.

Cerium oxide nanoparticles (CeNPs) have emerged as a potent therapeutic agent in the realm of wound healing, attributing their efficacy predominantly to their exceptional antioxidant properties. Mimicking the activity of endogenous antioxidant enzymes, CeNPs alleviate oxidative stress and curtail the generation of inflammatory mediators, thus expediting the wound healing process. Their application spans various disease models, showcasing therapeutic potential in treating inflammatory responses and infections, particularly in oxidative stress-induced chronic wounds such as diabetic ulcers, radiation-induced skin injuries, and psoriasis.

MYD88 L265P mutations identify a prognostic gene expression signature and a pathway for targeted inhibition in CLL.

The L265P somatic mutation in the Myeloid Differentiation Primary Response 88 (MYD88) gene is a recurrent mutation in chronic lymphocytic leukaemia (CLL). This mutation has functional effects in various haematological malignancies but its role in CLL remains to be fully elucidated. Here, we report that MYD88 L265P mutations are associated with mutated immunoglobulin heavy-chain gene (IGHV-M) status and that among IGHV-M patients, the presence of MYD88 L265P is associated with younger age at diagnosis.

Ofatumumab plus high dose methylprednisolone followed by ofatumumab plus alemtuzumab to achieve maximal cytoreduction prior to allogeneic transplantation for 17p deleted or TP53 mutated chronic lymphocytic leukemia.

We hypothesized that ofatumumab with sequential methylprednisolone - alemtuzumab would be an effective and tolerable regimen for patients with high-risk chronic lymphocytic leukemia (CLL) with TP53 dysfunction. Thirty CLL patients with TP53 dysfunction (15 treatment naive (TN), 15 relapsed/refractory (R/R)) were enrolled in this phase II study. Therapy included ofatumumab with methylprednisolone for 2-4 monthly cycles, then ofatumumab with alemtuzumab for 4-24 weeks, then allogeneic transplantation or maintenance.

RNA polymerase II depletion promotes transcription of alternative mRNA species.

Background: Cells respond to numerous internal and external stresses, such as heat, cold, oxidative stress, DNA damage, and osmotic pressure changes. In most cases, the primary response to stress is transcriptional induction of genes that assist the cells in tolerating the stress and facilitate the repair of the cellular damage. However, when the transcription machinery itself is stressed, responding by such standard mechanisms may not be possible.

Survival of Del17p CLL Depends on Genomic Complexity and Somatic Mutation.

Purpose: Chronic lymphocytic leukemia (CLL) with 17p deletion typically progresses quickly and is refractory to most conventional therapies. However, some del(17p) patients do not progress for years, suggesting that del(17p) is not the only driving event in CLL progression. We hypothesize that other concomitant genetic abnormalities underlie the clinical heterogeneity of del(17p) CLL.

The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism.

BCL2 blunts activation of the mitochondrial pathway to apoptosis, and high-level expression is required for chronic lymphocytic leukemia (CLL) survival. Venetoclax (ABT-199) is a small-molecule selective inhibitor of BCL2 currently in clinical trials for CLL and other malignancies. In conjunction with the phase 1 first-in-human clinical trial of venetoclax in patients with relapsed or refractory CLL (M12-175), we investigated the mechanism of action of venetoclax in vivo, explored whether in vitro sensitivity assays or BH3 profiling correlated with in vivo responses in patients, and determined whether loss of TP53 function affected responses in vitro and in vivo.

The Sub1 nuclear protein protects DNA from oxidative damage.

Reactive oxygen species are a by-product of aerobic metabolism that can damage lipid, proteins, and nucleic acids. Oxidative damage to DNA is especially critical, because it can lead to cell death or mutagenesis. Previously we reported that the yeast sub1 deletion mutant is sensitive to hydrogen peroxide treatment and that the human SUB1 can complement the sensitivity of the yeast sub1 mutant.

Obatoclax in combination with fludarabine and rituximab is well-tolerated and shows promising clinical activity in relapsed chronic lymphocytic leukemia.

Obatoclax is a small molecule mimetic of the BH3 domain of BCL-2 family proteins. This phase 1 study combining obatoclax with FR was undertaken in chronic lymphocytic leukemia (CLL) patients relapsed after at least one prior therapy. Obatoclax was given as a 3-h infusion on days 1 and 3 and escalated through three dose levels, with standard dose FR days 1-5.

Induction of a unique isoform of the NCOA7 oxidation resistance gene by interferon β-1b.

We demonstrate that interferon (IFN)-β-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins. IFN-β-1b induces NCOA7-AS (alternative start) expression in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and multiple sclerosis patients and human fetal brain cells, astrocytoma, neuroblastoma, and fibrosarcoma cells. NCOA7-AS is a previously undocumented IFN-β-inducible gene that contains only the last 5 exons of full-length NCOA7 plus a unique first exon (exon 10a) that is not found in longer forms of NCOA7.

Differential requirement for SUB1 in chromosomal and plasmid double-strand DNA break repair.

Non homologous end joining (NHEJ) is an important process that repairs double strand DNA breaks (DSBs) in eukaryotic cells. Cells defective in NHEJ are unable to join chromosomal breaks. Two different NHEJ assays are typically used to determine the efficiency of NHEJ.

UV damage regulates alternative polyadenylation of the RPB2 gene in yeast.

Alternative polyadenylation (APA) is conserved in all eukaryotic cells. Selective use of polyadenylation sites appears to be a highly regulated process and contributes to human pathogenesis. In this article we report that the yeast RPB2 gene is alternatively polyadenylated, producing two mRNAs with different lengths of 3'UTR.

[Optimization of expression conditions of recombinant Fuantai-03 and detection of its biological activities].

Fuantai-03(FAT-03), isolated from the Dasyatis akajei, has a strong antiangiogenic activity. The recombinant Fuantai-03 (GST/rFAT-03) fusion protein can be obtained with the DNA recombination technology. In this study, expression conditions of GST/rFAT-03 were optimized by response surface experimental design method.

Anti-microtubule activity of tubeimoside I and its colchicine binding site of tubulin.

Background: Tubeimoside I (TBMS1) was isolated from the tubers of Bolbostemma paniculatum (Maxim.) Franquet. TBMS1 shows potent anti-tumor activity.

Repair of glutamate-induced excitotoxic neuronal damage mediated by intracerebroventricular transplantation of neural stem cells in adult mice.

Objective: To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells (NSCs) in the adult mice subjected to glutamate-induced excitotoxic injury.

Methods: Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum (dpc). The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry.

[Tubeimoside I-induced ultrastructural changes of human cervical carcinoma HeLa cell line and the protective effect of cyclosporine A].

Objective: To observe the ultrastructural changes of HeLa cells in response to tubeimoside I (TBMS1) treatment and the protective effect of cyclosporine A (CsA), and explore the role of intrinsic apoptosis pathway in TBMS1-induced HeLa cell apoptosis.

Methods: HeLa cells were treated with TBMS1 (10-50 micromo/L) alone or in combination with 2 micromol/L CsA for 12 and 24 h and observed with transmission electron microscope (TEM) for the ultrastructural changes of the cells.

Results: TBMS1 induced apoptosis of HeLa cells in a concentration- and time-dependant manner.

[Saikosaponins inhibit increased glutamate and GABA expressions in the hippocampus of pentetrazole-induced slow kindling rats].

Objective: To study the effect of saikosaponins, the active ingredients of Bupleurum chinense DC. on glutamate and GABA expressions in the hippocampus of slow kindling rats induced by pentetrazole.

Methods: Forty-eight healthy Sprague-Dawley rats were randomly divided into 6 equal groups, namely the blank control group (group A), normal saline (NS) group (group B), sodium valproate group (group C), and 3 saikosaponins groups of high, medium and small doses (groups D, E, and F, respectively).

[Effect of saikosaponins on glial fibrillary acidic protein expression in hippocampal astrocytes of pentetrazole-induced chronic kindling rats].

Objective: To study the effect of saikosaponins, the active ingredients of Bupleurum chinense DC, on glial fibrillary acidic protein (GFAP) expression in hippocampal astrocytes of chronic kindling rats induced by pentetrazole (PTZ).

Methods: Forty-eight healthy Sprague-Dawley rats were randomized into 6 equal groups, namely the blank control group (Group A), normal saline group (Group B), sodium valproate group (Group C), and 3 saikosaponins groups of high, medium and small doses (Groups D, E, and F, respectively). The rats (except those in Group A) received intraperitoneal injection of PTZ to induce chronic kindling 1 h after the respective agents as indicated were administered intragastrically on a daily basis for 4 consecutive weeks.

[Effect of saikosaponins on epileptic seizure and EEG in pentetrazole-induced chronic kindling rats].

Objective: To study the effect of saikosaponins, the active ingredients of Bupleurum chinense DC, on epileptic seizure and EEG of pentetrazole (PTZ)-induced chronic kindling rats.

Methods: Forty-eight healthy Sprague-Dawley rats were randomly divided into 6 equal groups, namely the blank control group, normal saline (NS) group, sodium valproate (VPA) group, and 3 saikosaponins groups of high, medium and small doses. Except those in the blank control group, the rats in the other groups were all given different treatments as specified prior to intraperitoneal PTZ injection to induce kindling on a daily basis for 4 consecutive weeks.

[Role of mitochondria in Tubeimoside I-mediated apoptosis in human cervical carcinoma HeLa cell line].

Objective: To investigate the role of mitochondria in TBMS1-medited apoptosis of human cervical carcinoma HeLa cell line.

Method: Mitochondrial transmembrane potentia (deltapsim) was assayed by flow cytometry. Apoptotic induction by TBMS1 was determined by gel electrophoresis of fragmented DNA.

Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain.

The present study was conducted to investigate a possible protection of ferulic acid against excitotoxic effects of maternal intragastric (ig) administration of monosodium glutamate (MSG) at a late stage of pregnancy on developing mouse fetal brain. [(3)H]-labeled glutamate was used as radiotracer to study the effect of ferulic acid on distribution of MSG in mouse fetal brain. MSG dissolved in distilled water (2.

Role of mitochondria and mitochondrial cytochrome c in tubeimoside I-mediated apoptosis of human cervical carcinoma HeLa cell line.

Background: Tubeimoside I (TBMS1), a triterpenoid saponin, isolated from the tubers of Bolbostemma paniculatum, showed potent antitumor and antitumor-promoting effects. The objective of this study is to investigate the role of mitochondria and mitochondria cytochrome c in TBMS1-mediated apoptosis of human cervical carcinoma HeLa cell line.

Methods: Viability of HeLa cells was measured by MTT assay.

[Apoptosis of human nasopharyngeal carcinoma CNE-2Z cells induced by tubeimoside I].

Background & Objective: Tubeimu, Bolbostemma pani- culatum(Maxim.) Franquet (Cucurbitaceae), is a kind of traditional Chinese medicinal herb. Our previous studies revealed that tubeimoside I, a triterpenoid saponin isolated from the tubers of Bolbostemma paniculatum, showed potent antitumor effect.

[Cell cycle arrest and apoptosis induced by tubeimoside in HeLa cell].

Background & Objective: Tubeimoside, which is composed of tubeimoside I (79%) and II (21%), was isolated from the tubers of Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), a traditional Chinese medicine, "Tu-Bei-Mu". This study was designed to investigate the anti-tumor mechanism of tubeimoside.

Methods: Growth inhibition was measured by MTT assay.