Search

Background: Cutaneous T cell lymphoma (CTCL) is a T cell-derived non-Hodgkin lymphoma primarily affecting the skin, with treatment posing a significant challenge and low survival rates., Objective: In this study, we investigated the anti-cancer potential of Neosetophomone B (NSP-B), a fungal-derived secondary metabolite, on CTCL cell lines H9 and HH., Methods: Cell viability was measured using Cell counting Kit-8 (CCK8) assays. Apoptosis was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Applied Biosystems' high-resolution Human Transcriptome Array 2.0 was used to examine gene expression., Results: NSP-B induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and caspases. We observed downregulated expression of BUB1B, Aurora Kinases A and B, cyclin-dependent kinases (CDKs) 4 and 6, and polo-like kinase 1 (PLK1) in NSP-B treated cells, which was further corroborated by Western blot analysis. Notably, higher expression levels of these genes showed reduced overall and progression-free survival in the CTCL patient cohort. FOXM1 and BUB1B expression exhibited a dose-dependent reduction in NSP-B-treated CTCL cells.FOXM1 silencing decreased cell viability and increased apoptosis via BUB1B downregulation. Moreover, NSP-B suppressed FOXM1-regulated genes, such as Aurora Kinases A and B, CDKs 4 and 6, and PLK1. The combined treatment of Bortezomib and NSP-B showed greater efficacy in reducing CTCL cell viability and promoting apoptosis compared to either treatment alone., Conclusion: Our findings suggest that targeting the FOXM1 pathway may provide a promising therapeutic strategy for CTCL management, with NSP-B offering significant potential as a novel treatment option., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Tufting enteropathy (TE) is a rare autosomal recessive congenital enteropathy that usually requires long-term parenteral nutrition (PN). In the Arabic Peninsula, four distinct EPCAM mutations have been identified to cause TE. As consanguineous marriages are socially favored, pre-marital and pre-conception testing has become a critical disease prevention strategy. This study aimed to identify the pathogenic EPCAM mutations causing TE in Qatari families and determine possible genotype-phenotype correlations. Twenty-two TE patients from seven multiplex families with TE were identified. Blood samples were collected from patients and first-degree relatives. Exons of the gene were amplified and sequenced. Retrospective chart review and/or family interviews were conducted to determine phenotypic characteristics of the disease. Sequence analysis revealed a single, previously described c.499dup mutation in exon 5 of all families tested, suggesting a founder effect. Of the 18 patients whose full clinical information was available, three patients (17%) were off PN with a good quality of life, without intestinal transplantation, and one (6%) was receiving partial PN. Our patients with TE were severely stunted compared to a similar group of patients receiving long-term PN for short bowel syndrome, suggesting that this could possibly be due to TE rather than secondary to inadequate nutrition. Our study identified the EPCAM mutation c.499dup as the genetic defect causing TE in all the participant Qatari families. This finding should facilitate early diagnosis of TE and genetic counseling. Furthermore, it should aid in the prevention of TE through pre-marital screening, antenatal diagnosis, and pre-implantation genetic diagnosis., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Temtamy preaxial brachydactyly syndrome (TPBS) is an autosomal recessive rare disorder characterized by hyperphalangism of digits, facial dysmorphism, dental anomalies, sensorineural hearing loss, delayed motor and mental development, and growth retardation. Loss of function mutations have been recently reported in the CHSY1 gene to cause the TPBS. Here, we report a novel missense mutation (c.1897 G > A) in the CHSY1 gene in two TPBS patients from a consanguineous Pakistani family. The mutation predicted substitution of a highly conserved aspartate amino acid residue to asparagine at position 633 in the protein (D633N). Polyphen analysis supported the pathogenicity of D36N mutation. Our finding extends the body of recent evidence that supports the role of CHSY1 as a potential mediator of BMP signaling., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Enthusiasm for oocyte cryopreservation has been limited by poor pregnancy rates per thawed metaphase II (MII) oocytes (<4%) and low implantation rates per embryos. The reasons relate to technical limitations in the freezing process, and the fact that <40% of oocytes are euploid and unable to produce 'competent' embryos. Comparative genomic hybridization was performed on the first polar body (PB-1) of 323 MII oocytes retrieved from 16 donors. Of these, 111 were euploid, and were vitrified. Seventy-five of 78 vitrified oocytes (96%) survived warming and were fertilized using intracytoplasmic sperm injection. Thirty-one (41%) subsequently developed into expanded blastocysts, of which no more than two were subsequently transferred per uterus to 16 out of 19 prospective embryo recipients. Twelve of 19 (63%) recipients produced 17 healthy babies (eight singletons, three twins, and one set of triplets) One twin pregnancy miscarried in the late first trimester The birth rate per transfer of a maximum of two blastocysts to 16 recipients was 75%. The implantation rate per vitrified euploid oocyte was 27%. This study showed a six-fold improvement in pregnancy rate per cryopreserved oocyte over previous reports and a marked improvement in implantation rate. If independently validated, this approach could open the door to commercial egg cryobanking, significantly expanding women's reproductive choices.

Multiple displacement amplification (MDA) renders an increased quantity of genomic DNA available for comparative genomic hybridization (CGH), enabling it to be used to identify genomic imbalances in human blastomeres. The karyotypic lineage of 57 blastocysts derived from 11 ovum donors following ovarian stimulation was examined. CGH was performed on all first polar bodies, and linearly on corresponding second polar bodies and blastomeres. A diploid karyotype was propagated from the prefertilized oocyte to the embryo in 25 (44%) sets of analyses. In 32/57 sets (56%), aneuploidy was detected in the post-fertilized zygotes/embryos and in nine (28%) of such cases the aneuploidy was 'chaotic' (> or =3 chromosomes). In 4/57 cases (7%) mitotic aneuploidy was observed. CGH and fluorescence in-situ hybridization (FISH) were concurrently performed on two blastomeres removed from each of 44 embryos obtained from four patients. In 43 (98%) of these embryos there was a direct karyotypic correlation between nine-probe commercial FISH and CGH. CGH identified > or =15% more chromosomal abnormalities than through FISH alone. The linear propagation using MDA-CGH, of the same karyotypic abnormalities that affected the oocyte of origin, in the corresponding embryos, coupled with the fact that CGH confirmed the aneuploidies identified through FISH, validates the accuracy and reliability of CGH technology.

HLA-G is believed to play a pivotal role in the immunoprotection of the semiallogenic embryo. Its expression during pre- and early implantation is correlated with the cleavage rate of the embryo. Studies in congenic mice have revealed that mRNA of both the maternal and paternal haplotypes are present in zygotes and in embryos at all stages of development.

A retrospective cohort study was conducted on 201 women aged 28-44 years, each of whom underwent one cycle of IVF-embryo transfer with fresh, intracytoplasmic sperm injection (ICSI)-derived 7- to 10-cell embryos, transferred 72 h after oocyte retrieval. Samples of media surrounding separately cultured embryos were collected 46 h post-ICSI and stored for subsequent specific enzyme-linked immunosorbent assay. A total of 594 embryos (from own or donor oocytes) were transferred to 201 women. Group A comprised 159 recipients under 39 years and group B compromised 42 recipients aged 39-44 years. Groups A-1 and B-1 recipients had at least one embryo that tested above the geometric mean for soluble human leukocyte antigen-G (sHLA-G) ('positive expression') transferred. In groups A-2 and B-2, all embryos transferred expressed sHLA-G below the geometric mean ('negative expression'). In group A-1, 72/101 women (71%) achieved ultrasound confirmed (clinical), viable (cardiac activity observed) pregnancies. The implantation rate per embryo (IR) was 38%. In group A-2, 13/58 (22%) achieved viable clinical pregnancies. The IR was 9%. In group B-1, the viable clinical pregnancy rate was 52% (15/29) and the IR was 25% compared with a viable clinical pregnancy rate of 15% (2/13) and an IR of 5% in group B-2. The results of this study suggest that by selecting specific embryos for transfer based on their individual sHLA-G expression, pregnancy and implantation rates can be maximized while the number of embryos transferred can be reduced, thereby minimizing the incidence of high-order multiple pregnancies.

A practicable and reliable method for inducing labor in patients whose pregnancies are complicated by intrauterine death of the fetus is described. The method involves the intra-amniotic instillation of 30 mg of prostaglandin F2alpha with 60 gm of urea. Twenty patients had pregnancies ranging between 22 and 41 weeks and the estimated duration of fetal death ranged between two and eight weeks. Delivery was achieved within 24 hours in all cases. Side effects and complications were minimal. Plasma human placental lactogen (hPL) and progesterone concentrations, as well as several blood coagulation parameters (i.e., plasma fibrinogen, blood platelet count, and serum fibrin degradation products (FDP) concentrations), were measured immediately prior to induction of labor. The latter (i.e., coagulation factors) were repeated at parturition. The presence of residual viable placenta prior to induction did not influence the induction-delivery interval. No statistically significant alterations in blood coagulation parameters that could be attributed to the specific method of induction employed were noted.