Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma.

Background: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse.

Methods: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy.

Aldosterone is a possible new stimulating factor for promoting vascular calcification.

: Aldosterone is an important hormone in the renin-angiotensin-aldosterone system (RAAS), and playing a pivotal role in the development of hypertension, heart failure, and other cardiovascular diseases. : In this study, the role of the aldosterone in vascular calcification was underwent in rat model compared with other drugs. Vascular calcification, calcium concentration, activity of alkaline phosphatase (ALP), aldosterone, Urotensin II, mineralocorticoid receptor (MR) and Osteopontin (OPN) were detected or confirmed by the von Kossa staining, colorimetric assays, immunohistochemistry and radioimmunoassay, separately.

miR-765 inhibits the osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting BMP6 via regulating the BMP6/Smad1/5/9 signaling pathway.

Background: The process of bone repair is heavily dependent on the ability of human bone marrow mesenchymal stem cells (hMSCs) to undergo osteogenic differentiation. MicroRNAs have been shown to regulate this osteogenic process. This study aimed to investigate the role of miR-765 in the osteogenic differentiation of hMSCs.

Pirarubicin reduces USP22 expression by inhibiting CREB-1 phosphorylation in HeLa cells.

The expression of ubiquitin specific peptidase 22 (USP22) is upregulated in several types of cancer, and has been implicated in tumorigenesis. Pirarubicin (THP), an anthracycline antineoplastic drug, can induce apoptosis of several types of cancer cells. However, the molecular mechanisms underlying the action of THP remain to be elucidated.

Curcumin represses adipogenic differentiation of human bone marrow mesenchymal stem cells via inhibiting kruppel-like factor 15 expression.

Understanding the mechanisms of adipogenic differentiation may lead to the discovery of novel therapeutic targets for obesity. The natural plant polyphenol compound curcumin can improve obesity-associated inflammation and diabetes in obese mice. The role of curcumin in adipogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) is still unclear.

Design, synthesis, and evaluation of chalcone analogues incorporate α,β-Unsaturated ketone functionality as anti-lung cancer agents via evoking ROS to induce pyroptosis.

Chalcone, a natural structure, demonstrates many pharmacological activities including anticancer, and one promising mechanism is to modulate the generation of ROS. It has been known that pyroptosis is associated with anticancer effects, whereas there is fewer researches about ROS-mediated pyroptosis triggered by chemotherapy drugs. Moreover, incorporation of a α,β-unsaturated ketone unit into chalcone may be an effective strategy for development of chemotherapy drugs.

Design, synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds.

Molecular hybridization is considered as an effective tactic to develop drugs for the treatment of cancer. A series of novel hybrid compounds of isatin and Michael acceptor were designed and synthesized on the basis of association principle. These hybrid compounds were tested for cytotoxic potential against human cancer cell lines namely, BGC-823, SGC-7901 and NCI-H460 by MTT assay.

Bioinformatics analysis on the differentiation of bone mesenchymal stem cells into osteoblasts and adipocytes.

The present study aimed to screen several differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) for two types of mesenchymal stem cell (MSC) differentiation. Bone morphogenetic protein 6 (BMP‑6) and dexamethasone were used to induce MSCs towards osteoblastic differentiation or adipocytic differentiation. The t‑test in the Bioconductor bioinformatics software tool was used to screen DEGs and differentially expressed miRNAs in the two samples.

[Expression of miR-140-5p and prediction of its target gene in human mesenchymal stem cells during adipogenic differentiation].

Objective: To screen the differentially expressed miRNAs and their target genes in adipogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) to better understand the mechanism for regulating the balance between osteoblast and adipocyte differentiation.

Methods: Cultured hMSCs were induced for adipogenic differentiation, and at 0, 7, 14, and 21 days of induction, the cells were examined for miRNA and mRNA expression profiles using miRNA chip and transcriptome sequencing (RNA-seq) techniques. Correlation analysis was carried out for the miRNAs and mRNAs of potential interest.

Improving the safety of T-Cell therapies using an inducible caspase-9 gene.

Adoptive transfer of T cells can be an effective anticancer treatment. However, uncontrolled or unpredictable immediate or persistent toxic effects are a source of concern. The ability to conditionally eliminate aberrant cells in vivo is therefore becoming a critical step for the successful translation of this approach to the clinic.

Serial Activation of the Inducible Caspase 9 Safety Switch After Human Stem Cell Transplantation.

Activation of the inducible caspase 9 (iC9) safety gene by a dimerizing drug (chemical inducer of dimerization (CID) AP1903) effectively resolves the symptoms and signs of graft-versus-host disease (GvHD) in haploidentical stem cell transplant (HSCT) recipients. However, after CID treatment, 1% of iC9-T cells remain and can regrow over time; although these resurgent T cells do not cause recurrent GvHD, it remains unclear whether repeat CID treatments are a safe and feasible way to further deplete residual gene-modified T cells should any other adverse effects associated with them occur. Here, we report a patient who received an infusion of haploidentical iC9-T cells after HSCT and subsequently received three treatments with AP1903.

Clonal Dynamics In Vivo of Virus Integration Sites of T Cells Expressing a Safety Switch.

Safety switches are becoming relevant for the clinical translation of T-cell-based immunotherapies. In patients receiving an allogeneic hematopoietic stem cell transplant, the inducible caspase-9 gene (iC9) safety switch expressed by donor-derived T lymphocytes efficiently controls acute graft versus host disease (GvHD). However, in vivo elimination of iC9-T cells by the chemical inducer of dimerization (CID) that activates the iC9 protein is incomplete.

PKA/CREB regulates the constitutive promoter activity of the USP22 gene.

The human ubiquitin-specific processing enzyme 22 (USP22) plays a crucial role in regulating cell cycle processes and its overexpression has been linked to tumor progression. However, the mechanisms leading to USP22 transcriptional activation in human cancer cells are still unclear. Previously, we characterized the 5'-flanking sequence of the human USP22 gene and found a potential CREB/ATF binding site within the basic promoter region.

[Cloning of IPO8 promoter and analysis of its transcription activity].

Objective: To clone 5' untranslated region of human IPO8 gene and determine its transcription activity.

Methods: We used 5' rapid amplification of cDNA ends (RACE) analysis to identify the IPO8 transcription start site (TSS), and amplified series truncated 5' UTR fragment containing transcription start site. The PCR productions were inserted into luciferase report vector pGL3- Basic.

[Wortmannin and U0126 inhibit the promoting effect of insulin on differentiation of skeletal myoblasts in rats].

Objective: To verify whether insulin promotes the differentiation of skeletal myoblasts into myocytes and whether wortmannin and U0126 inhibit the promoting effect with an attempt to explore the molecular mechanisms of inducing the differentiation of muscular cells in rats.

Methods: Primary skeletal myoblasts were separated and cultured from rats, and then were treated in DMEM containing various concentrations of insulin. The morphology of cells was monitored under a phase-contrast microscope.

Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene.

Adoptive transfer of donor-derived T lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT) without the risk for uncontrolled graft versus host disease (GvHD). Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. We now report the long-term follow-up of 10 patients infused with such safety switch-modified T cells.

[Construction and identification of recombinant adenovirus of muramidase-released protein gene fragment from Streptococcus suis type 2].

Objective: To construct and identify the recombinant adenovirus of muramidase-released protein (MRP) gene fragment from Streptococcus suis type 2 (SS2).

Methods: The specific primers were designed based on the sequence of MRP gene fragment. The MRP gene fragment (467-1351 bp) was amplified by PCR method with genomic DNA of SS2 as a template.

A Th1-inducing adenoviral vaccine for boosting adoptively transferred T cells.

Although the benefits of adoptive T-cell therapy can be increased by prior lymphodepletion of the recipient, this process usually requires chemotherapy or radiation. Vaccination with antigens to which the transferred T cells respond should be a less toxic means of enhancing their activity, but to date such vaccines have not been effective. We, therefore, determined which characteristics an adenoviral vaccine has to fulfill to optimally activate and expand adoptively transferred antigen-specific T cells in vivo.

Decreased ENaC expression compensates the increased NCC activity following inactivation of the kidney-specific isoform of WNK1 and prevents hypertension.

Mutations in WNK1 and WNK4 lead to familial hyperkalemic hypertension (FHHt). Because FHHt associates net positive Na(+) balance together with K(+) and H(+) renal retention, the identification of WNK1 and WNK4 led to a new paradigm to explain how aldosterone can promote either Na(+) reabsorption or K(+) secretion in a hypovolemic or hyperkalemic state, respectively. WNK1 gives rise to L-WNK1, an ubiquitous kinase, and KS-WNK1, a kinase-defective isoform expressed in the distal convoluted tubule.

Regulation of WNK1 expression by miR-192 and aldosterone.

WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily. Greater WNK1 expression associates with higher BP. A combination of promoters, enhancers, repressors, and insulators regulate WNK1 expression, but whether microRNAs also modulate WNK1 expression is unknown.

[Correlation study on serum adiponectin abnormity with adiponectin gene polymorphisms in hypertensive patients of phlegm-dampness constitution].

Objective: To explore the difference of serum adiponectin (APN) level in hypertensive patients of phlegm-dampness constitution (PDC) and in those of non-PDC, as well as its association with APN gene polymorphisms.

Methods: Serum APN levels in 250 hypertensive patients (137 of PDC and 113 of non-PDC) were determined, and a correlation study was performed on 8 selected single nucleotide polymorphism (SNP) of APN gene.

Results: Significant differences of serum APN levels were observed between PDC and non-PDC patients (5.