Paired comparisons of venetoclax concentration in cerebrospinal fluid, bone marrow, and plasma in acute leukemia patients.

Venetoclax, a small molecule inhibitor of BCL-2, has demonstrated efficacy in treating acute leukemias and has been recommended as one of the first-line anti-leukemia therapies. Although venetoclax has been suggested to probably possess the ability to penetrate the central nervous system (CNS), current data to elucidate the characteristics of venetoclax in cerebrospinal fluid (CSF), bone marrow (BM), and plasma are still lacking. This study investigated the real-world characteristics of venetoclax concentrations in CSF, BM, and plasma in acute leukemia patients.

Gallic acid attenuates murine ulcerative colitis by promoting group 3 innate lymphocytes, affecting gut microbiota, and bile acid metabolism.

Gallic acid (GA), a plant phenol that is widely distributed in fruits and vegetables, and exhibits a protective role against ulcerative colitis (UC). UC is an inflammatory disease characterized by immune response disorders. However, the role and mechanism of action of GA in gut immunity remain unknown.

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial.

Background: Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed.

The complete mitochondrial genome and phylogenetic analysis of Li, Mao & Lu, 2002 (Cypriniformes: Xenocyprididae).

is a native and rare fish in Yunnan. In this study, the complete mitochondrial genome of was sequenced and published for a total of 16,614 bp, including 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and one control region. The phylogenetic analysis based on the complete mitochondrial genome showed that belongs to the clade of the genus and was sister to the clade of .

Characteristics and Risk Factors of Ultra-High-Risk Patients with Newly Diagnosed Multiple Myeloma.

Objective: To investigate the clinical characteristics and risk factors of ultra-high-risk (UHR) patients with newly diagnosed multiple myeloma (MM).

Methods: We screened UHR patients with a survival of less than 24 months and we selected patients with a concurrent survival of more than 24 months as a control group. We retrospectively analyzed the clinical characteristics of UHR patients with newly diagnosed MM and screened related risk factors.

Sovleplenib (HMPL-523), a novel Syk inhibitor, for patients with primary immune thrombocytopenia in China: a randomised, double-blind, placebo-controlled, phase 1b/2 study.

Background: Spleen tyrosine kinase (Syk) inhibitor is a treatment option for primary immune thrombocytopenia. We aimed to evaluate the safety, tolerability, pharmacokinetics, preliminary activity, and recommended phase 2 dose of sovleplenib in patients with primary immune thrombocytopenia.

Methods: This randomised, double-blind, placebo-controlled, phase 1b/2 study was conducted at nine hospitals in China.

Low Barthel index score is a poor prognostic factor for newly diagnosed multiple myeloma patients.

The basic activities of daily life may affect the prognosis of multiple myeloma (MM) patients and the Barthel index (BI) is currently the most widely used tool to evaluate basic activities of daily life, but few studies have evaluated its prognostic value in MM. We retrospectively enrolled patients with newly diagnosed MM and analyzed the association between the BI and the survival of newly diagnosed MM patients. We totally analyzed 538 patients and found that median overall survival (OS) and progression-free survival (PFS) were significantly shorter in the low BI (≤ 85) group compared with the high BI (> 85) group.

Prognostic value of t(4;14) translocation in newly diagnosed multiple myeloma patients in novel agent era.

Objective: To evaluate the prognostic value of t(4; 14) translocation for newly diagnosed multiple myeloma (MM) patients in the novel agent era.

Methods: We retrospectively analyzed 606 newly diagnosed MM patients treated with novel agents. The propensity score matching technique was used to reduce the bias between groups.

Newly diagnosed multiple myeloma patients with CD56 expression benefit more from autologous stem cell transplantation.

Background: Several studies showed that lack of CD56 expression was a poor prognostic factor for patients with newly diagnosed multiple myeloma (NDMM). However, other studies were not able to confirm the prognostic value of CD56 in NDMM. This study aimed to evaluate the prognostic value of CD56 expression for patients with NDMM who received autologous stem cell transplantation (ASCT).

Mechanisms underlying synergism between circularized tumor necrosis factor-related apoptosis inducing ligand and bortezomib in bortezomib-sensitive or -resistant myeloma cells.

Mechanisms underlying interactions between a novel, clinically relevant circularized tumor necrosis factor-related apoptosis inducing ligand (TRAIL) agonist, circularly permuted TRAIL (CPT) have been examined in multiple myeloma (MM) cells sensitive or resistant to bortezomib (BTZ). Various MM cell lines for example, U266, including those resistant to bortezomib-resistant U266 cells were exposed to low nanomolar concentrations of bortezomib ± CPT and apoptosis monitored. Circularly permuted TRAIL and bortezomib synergistically induced apoptosis in both BTZ-naïve and -resistant cells.

Structural Characterization and Immunoenhancing Effects of a Polysaccharide from the Soft Coral Lobophytum sarcophytoides.

Previous studies on the soft coral Lobophytum sarcophytoides (Lobophytum sp.) are mainly about small molecules, and there has been no systematic research on polysaccharides. In the study, a novel polysaccharide (LCPs-1-A) with immunoenhancing functions was successfully extracted and purified from the soft coral Lobophytum sp.

Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells.

Background: Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of ovarian cancer to cisplatin, and to demonstrate the underlying mechanism.

The complete mitochondrial genome of Regan, 1907 (Siluriformes: Siluridae), a native catfish in Fuxian Lake.

In this study, the whole mitochondrial genome of was reported to be 16,518 bp in length, including 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and one control region. The phylogenetic analysis based on 13 protein-coding genes showed that was sister to clade of and . A total of 81 bases differences were identified in COI barcoding region, which could be used for species identification in catfish.

Deep and partial immunoparesis is a poor prognostic factor for newly diagnosed multiple myeloma patients.

We retrospectively analyzed immunosuppression status in 287 newly diagnosed multiple myeloma (MM) patients and assessed the prognostic value of immunoparesis on survival. Deep immunoparesis was defined that one of uninvolved immunoglobulins was below 50% the lower limit of normal ranges, partial immunoparesis was defined at least two suppressed uninvolved immunoglobulins. We found that patients with deep and partial immunoparesis had a significantly shorter median overall survival (OS) and progression-free survival (PFS).

The IAP antagonist birinapant potentiates bortezomib anti-myeloma activity in vitro and in vivo.

Background: Mechanisms by which Smac mimetics (SMs) interact with proteasome inhibitors (e.g., bortezomib) are largely unknown, particularly in multiple myeloma (MM), a disease in which bortezomib represents a mainstay of therapy.

Immunoparesis recovery 1 year after ASCT is independently associated with favorable survival in patients with symptomatic multiple myeloma who undergo autologous stem cell transplantation.

Immunoparesis is defined as a reduction in the levels of one, two, or three uninvolved immunoglobulins. However, there are very limited data on the incidence and prognostic significance of immunoparesis recovery 1 year after autologous stem cell transplantation (ASCT) in MM. We reviewed medical records of de novo MM patients who received ASCT at Beijing Chao Yang hospital.

Recombinant human thrombopoietin improves the efficacy of intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor in mobilizing peripheral blood stem cells in patients with multiple myeloma: A cohort study.

The combination of intermediate-dose cyclophosphamide (ID-CTX) and granulocyte colony-stimulating factor (G-CSF) fails to mobilize peripheral blood stem cells (PBSCs) in approximately 20% of treated patients with multiple myeloma (MM).In this cohort study, patients with MM underwent PBSC mobilization with either an ID-CTX plus G-CSF plus recombinant human thrombopoietin (rhTPO) regimen (72 patients; TPO group), or an ID-CTX plus G-CSF regimen (70 patients; non-TPO group).In the TPO group, the median CD34+ harvest was 5.

Positive transcription elongation factor b (P-TEFb) is a therapeutic target in human multiple myeloma.

The role of the positive RNA Pol II regulator, P-TEFb (positive transcription elongation factor b), in maintenance of the anti-apoptotic protein Mcl-1 and bortezomib (btz) resistance was investigated in human multiple myeloma (MM) cells. Mcl-1 was up-regulated in all MM lines tested, including bortezomib-resistant lines, human MM xenograft mouse models, and primary CD138 MM cells. Mcl-1 over-expression significantly reduced bortezomib lethality, indicating a functional role for Mcl-1 in bortezomib resistance.

A Phase1b Dose Escalation Study of Recombinant Circularly Permuted TRAIL in Patients With Relapsed or Refractory Multiple Myeloma.

Objectives: Circularly permuted tumor necrosis factor-related apoptosis-inducing ligand (CPT), or CPT, is a novel antitumor drug candidate. This phase 1b study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of single-agent CPT in patients with relapsed or refractory multiple myeloma (RRMM), and aimed to identify the recommended dose for the phase 2 study.

Materials And Methods: Patients received single or multiple doses (once daily for 5 consecutive days per 21-d cycle) of CPT intravenous infusion at doses of 5, 6.

Arsenic trioxide potentiates sensitivity of multiple myeloma cells to lenalidomide by upregulating cereblon expression levels.

The mechanism of the anti-myeloma effect of the immunomodulatory drug lenalidomide relies upon the binding of lenalidomide or an analogue to cereblon (CRBN) ubiquitin ligase, which inhibits it and results in the degradation of Ikaros-family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). To determine whether the traditional Chinese medicine arsenic trioxide, could potentiate sensitivity of multiple myeloma (MM) cells to lenalidomide and identify the mechanism by which this happens, the present study investigated how arsenic trioxide affected CRBN on MM cell lines and examined the anti-myeloma effect and mechanism in the combination of arsenic trioxide and lenalidomide. The present study revealed that arsenic trioxide upregulates the transcription and protein levels of CRBN, the anti-myeloma target of lenalidomide, thus potentiating the sensitivity of multiple myeloma cells to lenalidomide and enhancing the lenalidomide-dependent degradation of IKZF1 and IKZF3.

Autoantibodies against β-adrenergic receptor: response to induction therapy with bortezomib-containing regimens for multiple myeloma patients.

This study aims to investigate the predictive value of pre-chemotherapy β1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of β1R-AABs were detected by ELISA.

Human iPSC-MSC-Derived Xenografts Modulate Immune Responses by Inhibiting the Cleavage of Caspases.

Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs. However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear.