Search

High-dose chemotherapy and stem cell transplantation are the best treatment options in patients with multiple myeloma. Numerous medicines have been studied as a maintenance treatment after transplantation. Still, the use of medications that, in addition to their maintenance properties, eliminate or delay relapse of the disease has always been researchers' purpose. Therefore, this study was performed to evaluate the efficacy of MST-312 after stem cell transplantation in patients with multiple myeloma. For this purpose, 73 patients with multiple myeloma after stem cell transplantation were studied. Thirty-five patients were in the case group, and 37 patients were in the control group. The case group was treated with 100 mg/day MST-312. Stem cell survival was evaluated in the two groups. Also, the expression of TNFα and IL-6 genes were evaluated by the Real-time PCR technique. The results showed no significant difference between the two groups in terms of stem cell survival in the first year (P=0.72) and second years of treatment (P=0.66). But there was a significant difference between the two groups regarding progression-free survival (PFS) in the first year (P=0.041) and the second year (P=0.029). These results indicate that MST-312 inhibits the progress of the disease by inhibiting the telomerase activity of myeloma cells. Genetic evaluations also showed that IL-6 and TNF-α genes were significantly reduced in the case group. Therefore, it could be suggested that MST-312 has a selective inhibitory effect on myeloma cell growth and can be indicated as a suitable candidate for treating multiple myeloma.

Anti-lipopolysaccharide factors (ALF) is an important antimicrobial peptide and critical effector molecule with a broad spectrum of antimicrobial activities in crustaceans. In addition to the previously reported five ALFs (MnALF1-5), another three ALFs [MnALF1, which is different from MnALF1 (ALF02818) that has been reported; MnALF6; and MnALF7] and an isoform of MnALF4 (MnALF4-isoform2) were newly identified from Macrobrachium nipponense in this study. MnALF6 has 134 amino acids and one single nucleotide polymorphism (SNP) in MnALF6 resulted in the change of 107th amino acid from E to D. Intron 1 retention produced longer transcript of MnALF6. The full length of MnALF7 has 691 bp with a 363 bp ORF encoding 120 amino acid protein. Three SNPs in MnALF2 resulted in the conversion of amino acids at positions 70, 73, and 91 from T

Bursicon (burs) is a neuropeptide hormone composed of two cystine knot-like proteins (burs α and burs β) that regulate the tanning of the cuticle of insect epidermis and the extension of new wings. In insects, burs regulate the secretion of antimicrobial peptides (AMPs). In this study, we characterized burs homodimers (named Mnbursα and Mnbursβ) and explored their roles in the synthesis of AMPs in Macrobrachium nipponense for the first time. The full cDNA lengths of Mnbursα and Mnbursβ are 946 and 1357 bp containing 444 and 414 nucleotides of an open reading frame that encodes 147 and 137 amino acids of protein, respectively. Tissue distribution analysis showed that Mnbursα and Mnbursβ were widely expressed in various tested immune tissues, and they were most prominently expressed in the hepatopancreas. At multiple time points after being challenged by bacteria (Vibrio parahaemolyticus and Staphylococcus aureus) and virus (white spot syndrome virus), the expression levels of Mnbursα and Mnbursβ in the gills and stomach were significantly upregulated, suggesting that pathogen invasion was involved in regulating the transcription of Mnbursα and Mnbursβ. We further explored the relationship between the burs homodimers and the synthesis of AMPs [crustin (Cru), anti-lipopolysaccharide factor (ALF), and carcinin (Car)] through RNA interference. Knockdown of Mnbursα and Mnbursβ evidently downregulated the expression of six tested AMPs (Cru1, Cru2, Cru3, ALF1, ALF3, and Car1). Recombinant r-Mnbursα-α and r-Mnbursβ-β proteins could obviously increase the expression levels of the six AMPs, indicating that Mnbursα and Mnbursβ play positive regulatory roles in the synthesis of AMPs. NF-κB transcription factors are essential in the production of AMPs in humoral immunity. Further research showed that the upregulation roles of r-bursicon homodimers on three tested AMPs (Cru1, ALF1, and ALF3) disappeared after silencing the MnRelish transcription factor. Our findings suggest that the synthesis of AMPs is induced by the bursicon homodimers via Relish in the innate immunity of M. nipponense. This study provides new insights in the function of bursicon in the immune system of crustaceans.

Hepatopancreatic necrosis syndrome (HPNS) severely threatens the development of Eriocheir sinensis farming. To date, no consensus has been reached about the etiology and pathogenesis of HPNS. In this study, we investigated the effects of HPNS on the copper-containing respiratory protein (hemocyanin), the ecdysone inducible transcription factor (E75), and the zinc finger-containing transcription factor (Kruppel). We also determined the relationship between hemocyanin and the two transcription factors. Seven hemocyanin variants, four E75 isoforms, and a Kruppel-like factor were characterized in E. sinensis. The 3′ and 5′ ends of hemocyanin possessed molecular diversity, which was apparently associated with its multifunctionality. Four E75 isoforms were generated by the alternative splicing of the 5′ exons, and they originated from a single copy gene. Hemocyanins, EsE75, and EsKruppel were mainly expressed in the hepatopancreas, which is the most primary organ for the clinical characterization of HPNS. The expression of the hemocyanins and two transcriptional factors (EsE75 and EsKruppel) were significantly decreased and increased in the crabs with HPNS, respectively. Moreover, silencing of EsE75 and EsKruppel resulted in an evident increase in the synthesis of hemocyanins, indicating that EsE75 and EsKruppel acted as the transcription repressor of the hemocyanin gene. However, the detailed mechanisms by which E75 and Kruppel regulated the transcription of hemocyanin in E. sinensis need to be more thoroughly studied in the future. This study provides new information on hemocyanin, E75, and Kruppel that were influenced by HPNS in E. sinensis. The results will help to enhance the understanding of the causes and pathogenesis of HPNS.

Spätzle, an extracellular ligand of the Toll receptor, is involved in the innate immunity of crustaceans. In this study, four Spätzle genes were cloned from Macrobrachium nipponense and designed as MnSpz1, MnSpz2, MnSpz2-isoform, and MnSpz3. The coding region of the four Spätzle genes all contained one intron and two exons, and they were predicted to be produced by gene duplication based on sequence similarities and phylogenetic tree. The predicted MnSpz1, MnSpz2, and MnSpz3 proteins all contained a signal peptide and a Spätzle domain. No signal peptide but a Spätzle domain existed in MnSpz2-isoform because of frameshift mutation caused by 50 bp nucleotide deletion compared with MnSpz2. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis showed that MnSpz1, MnSpz2, and MnSpz3 were expressed in all the detected tissues of M. nipponense, and MnSpz2 was found to be the major isoform in the heart, gills, stomach, and intestine. After stimulation by Vibrio parahaemolyticus, Staphylococcus aureus, or White spot syndrome virus (WSSV), the expression levels of MnSpz1, MnSpz2, and MnSpz3 changed. Given the high similarities among MnSpz1-3, RNA interference (RNAi) using dsRNA of MnSpz1 inhibited the expression of the three Spätzle genes (MnSpz1, MnSpz2 and MnSpz3). Silencing of MnSpz1-3 down-regulated the expression levels of nine antimicrobial peptide (AMP) genes in M. nipponense. After Knockdown of MnSpzs, the number of V. parahaemolyticus, S. aureus and WSSV copies in M. nipponense increased significantly in vivo. Our results suggest that Spätzles are involved in the innate immunity of M. nipponense. The expansion of MnSpz genes through gene duplication is beneficial to enhance the innate immune defense ability of M. nipponense.

The ICl-induced cyclization of heteroatom-substituted alkynones provides a simple, highly efficient approach to various 3-iodochromones and analogues. This process is run under mild conditions, tolerates various functional groups, and generally provides chromones in good to excellent yields. Subsequent palladium-catalyzed transformations afford a rapid increase in molecular complexity and a convenient preparation of a wide range of functionally substituted chromones, furans, and polycyclic compounds. Iodothiochromenones and iodoquinolinones are also prepared by similar ICl-induced cyclizations.

The Pd(II)-catalyzed reaction of arylboronic acids and internal alkynes provides a convenient route to a wide variety of tetrasubstituted olefins. The reaction is conducted in DMSO using molecular O2 as an oxidant in the absence of any base. The reaction involves the cis addition of two aryl groups from the arylboronic acid to opposite ends of the triple bond of the internal alkyne. The synthesis tolerates a wide variety of functional groups, including alcohol, aldehyde, ester, TMS, and acetal groups. Electron-rich dialkylacetylenes, such as 4-octyne, provide highly substituted 1,3-dienes in moderate yields. The very mild O2/DMSO conditions also afford good to excellent yields of biaryls by the homocoupling of arylboronic acids.

[Reaction: see text] Tetrasubstituted olefins are readily prepared by the Pd-catalyzed cis addition of two aryl groups from an arylboronic acid to opposite ends of the triple bond of internal alkynes. The synthesis proceeds under very mild reaction conditions and tolerates a wide variety of functional groups, including alcohol, aldehyde, ester, TMS, and acetal groups.

The palladium-catalyzed reaction of simple arenes and nitriles provides good to excellent yields of aryl ketones or the corresponding hindered imines. The addition of a small amount of DMSO increases the yields dramatically. Both intermolecular and intramolecular examples of this process are successful. This novel chemistry is believed to involve palladium-catalyzed C-H activation, followed by carbopalladation of the nitrile.

An efficient, regio- and stereoselective palladium-catalyzed route to tetrasubstituted olefins has been developed, which involves the intermolecular coupling of an aryl iodide, an internal alkyne, and an arylboronic acid. The reaction involves cis-addition of the aryl group from the aryl halide to the less hindered or less electron-poor end of the alkyne, while the aryl group from the arylboronic acid adds to the other end. [reaction: see text]