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Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily. BMPs play crucial roles in embryogenesis and bone remodeling. Recently, BMP signaling has been found to have diverse effects on different types of tumors. In this review, we summarized the effects of BMP signaling on gynecologic cancer. BMP signaling has tumor‐promoting effects on ovarian cancer (OC) and endometrial cancer (EC), whereas it has tumor‐suppressing effects on uterine cervical cancer (UCC). Interestingly, EC has frequent gain‐of‐function mutations in ACVR1, encoding one of the type I BMP receptors, which are also observed in fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. Little is known about the relationship between BMP signaling and other gynecologic cancers. Tumor‐promoting effects of BMP signaling in OC and EC are dependent on the promotion of cancer stemness and epithelial–mesenchymal transition (EMT). In accordance, BMP receptor kinase inhibitors suppress the cell growth and migration of OC and EC. Since both cancer stemness and EMT are associated with chemoresistance, BMP signaling activation might also be an important mechanism by which OC and EC patients acquire chemoresistance. Therefore, BMP inhibitors are promising for OC and EC patients even if they become resistant to standard chemotherapy. In contrast, BMP signaling inhibits UCC growth in vitro. However, the in vivo effects of BMP signaling have not been elucidated in UCC. In conclusion, BMP signaling has a variety of functions, depending on the types of gynecologic cancer. Therefore, targeting BMP signaling should improve the treatment of patients with gynecologic cancer. [ABSTRACT FROM AUTHOR]

Positive peritoneal cytology is a poor prognostic factor in patients with advanced endometrial cancer. Suspicious positive peritoneal cytology (class III) is commonly encountered in clinical practice. However, no standard treatment protocol exists for its management. Here, we investigated a possible relationship between suspicious positive peritoneal cytology, disease stage, risk factors, and endometrial cancer prognosis. We included patients diagnosed with endometrial cancer who underwent total hysterectomy and peritoneal cytology at the University of Tokyo Hospital between 2008 and 2022. Overall, 670 patients were included in the analyses; both demographic and clinical data of the patients were collected. The proportion of patients with lymph node metastasis was significantly different between peritoneal cytology groups, showing lymph node metastasis to be more extensive in patients with positive or suspicious positive peritoneal cytology than in patients with negative peritoneal cytology (p < 0.05). Thirty-nine patients had suspicious positive peritoneal cytology. Omental resection and biopsy were performed in 16 cases. No case of omental metastasis was found. Among patients with suspected ascites cytology, no patient experienced symptom recurrence or death. Therefore, monitoring lymph node metastasis in suspicious positive cases is essential. Moreover, a change of treatment method based on the finding of suspected positive peritoneal cytology is not necessary. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) play an important role in development. Twisted gastrulation BMP signaling modulator 1 (TWSG1) was initially identified as a regulator of the dorsoventral axis formation in Drosophila. The mechanism of BMP signaling modulation by TWSG1 is complex. TWSG1 inhibits BMP signaling by binding to BMP ligands including BMP4, whereas it enhances signaling by interacting with Chordin, a BMP antagonist. Therefore, TWSG1 can act as both a BMP agonist and antagonist. TWSG1 has various functions ranging from embryogenesis to cancer progression. TWSG1 knockout mice showed neural, craniofacial, and mammary defects. TWSG1 also regulated erythropoiesis and thymocyte development. Furthermore, the relationship between TWSG1 and cancer has been elucidated. Allelic loss of TWSG1 was detected in colorectal cancer. TWSG1 expression was upregulated in papillary thyroid carcinoma and glioblastoma but downregulated in gastric and endometrial cancers. TWSG1 suppressed BMP7-enhanced sphere formation and migration in endometrial cancer cells, indicating its tumor-suppressive role. Further studies are required to clarify the TWSG1 function and its association with BMP signaling in cancer development. Finally, TWSG1 is abundantly expressed in human and mouse ovaries and sustains follicular growth in rodent ovaries. Thus, TWSG1 has various functions ranging from fertility to cancer. Therefore, TWSG1 signaling modulation may be beneficial in treating specific diseases such as cancer. [ABSTRACT FROM AUTHOR]

Introduction: Primary hyperparathyroidism (PHPT) occurs as part of familial syndromes, including CDC73-related disorders caused by germline pathogenic variants of the CDC73 gene, particularly in early adulthood. Herein, we report a familial case of a whole germline CDC73 deletion discordant for PHPT. Case Description: A 15-year-old boy was admitted to our hospital because of persistent nausea and vomiting. Laboratory tests showed hypercalcemia (13.6 mg/dL), hypophosphatemia (2.4 mg/dL), and elevated intact PTH level (149 pg/mL). Imaging studies showed an enlarged single parathyroid gland. Thus, the diagnosis of PHPT was made. Microarray analysis of peripheral blood DNA showed a 3.4-Mb heterozygous deletion of 1q31 encompassing 11 genes, including CDC73. Total thyroidectomy/parathyroidectomy was performed; histology was compatible with parathyroid adenoma without any evidence of malignancy. DNA sequencing of the removed adenoma confirmed a hemizygous nonsense variant in the CDC73 gene in a mosaic manner, which was potentially involved in parathyroid tumorigenesis as the "second hit." Importantly, the same deletion was identified in his 52-year-old father who had an unremarkable medical history. Conclusions: These data clearly demonstrate the Knudson two-hit theory from a molecular viewpoint. Phenotypic variability and incomplete penetrance of CDC73-related disorders, even if caused by a gross deletion, should be noted in a clinical setting. [ABSTRACT FROM AUTHOR]

A chemical sensor for cysteine (Cys) was fabricated based on a fluorescent oligo( p-phenylene ethynylene)s (OPEs) and OPE-graphene oxide (GO) composite. OPE with cyanoacrylate terminal groups were synthesized by a Pd-catalyzed Sonogashira coupling reaction and Knoevenagel condensation for use as a chemical sensor for Cys. The optical properties and Cys sensing capability of the cyanoacrylate modified OPE and OPE-GO composite were investigated. In addition of Cys, the fluorescence of OPE was blue-shifted and decreased (fluorescence turn-off), while the fluorescence of the OPE-GO composite was enhanced (fluorescence turn-on). Thus, OPE with cyanoacrylate terminal groups and OPE-GO composite acts a highly sensitive fluorescent chemical sensor for Cys. [ABSTRACT FROM AUTHOR]

Bordetella holmesii causes both invasive and respiratory diseases in humans. Although the number of cases of pertussis-like respiratory illnesses due to B. holmesii infection has increased in the last decade worldwide, little is known about the virulence factors of the organism. Here, we analyzed a B. holmesii isolate that forms large aggregates and precipitates in suspension, and subsequently demonstrated that the autoagglutinating isolate is deficient in Bordetella intermediate protein A (BipA) and that this deletion is caused by a frame-shift mutation in the bipA gene. A BipA-deficient mutant generated by homologous recombination also exhibited the autoagglutination phenotype. Moreover, the BipA mutant adhered poorly to an abiotic surface and failed to form biofilms, as did two other B. holmesii autoagglutinating strains, ATCC 51541 and ATCC 700053, which exhibit transcriptional down-regulation of bipA gene expression, indicating that autoagglutination indirectly inhibits biofilm formation. In a mouse intranasal infection model, the BipA mutant showed significantly lower levels of initial lung colonization than did the parental strain (P < 0.01), suggesting that BipA might be a critical virulence factor in B. holmesii respiratory infection. Together, our findings suggest that BipA production plays an essential role in preventing autoagglutination and indirectly promoting biofilm formation by B. holmesii. [ABSTRACT FROM AUTHOR]

Whooping cough due to Bordetella pertussis is increasing in incidence, in part due to accumulation of mutations which increase bacterial fitness in highly vaccinated populations. Polymorphisms in the pertussis toxin, ptxA and ptxB genes, and the pertactin, prn genes of clinical isolates of Bordetella pertussis collected in Cincinnati from 1989 through 2005 were examined. While the ptxA and prn genotypes were variable, all 48 strains had the ptxB2 genotype; ptxB1 encodes glycine at amino acid 18 of the S2 subunit of pertussis toxin, while ptxB2 encodes serine. We investigated antigenic and functional differences of PtxB1 and PtxB2. The S2 protein was not very immunogenic. Only a few vaccinated or individuals infected with B. pertussis developed antibody responses to the S2 subunit, and these sera recognized both polymorphic forms equally well. Amino acid 18 of S2 is in a glycan binding domain, and the PtxB forms displayed differences in receptor recognition and toxicity. PtxB1 bound better to the glycoprotein, fetuin, and Jurkat T cells in vitro, but the two forms were equally effective at promoting CHO cell clustering. To investigate in vivo activity of Ptx, one μg of Ptx was administered to DDY mice and blood was collected on 4 days after injection. PtxB2 was more effective at promoting lymphocytosis in mice. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examines the regulatory mechanisms of the transmembrane protein osteoactivin. It mentions several techniques including liquid chromatography, polyacrylamide gel electrophoresis and mass spectrometry which are used as the research methodologies. The result reveals that osteoactivin is released by proteolytic cleavage at both the cell surface and the intramembrane space.

Studies the interaction of a tea catechin, epigallocatechin gallate with the model membrane of dimyristoylphosphatidylcholine (DMPC) by solid-state P and H nuclear magnetic resonance spectroscopy. P chemical shift anisotropy of the DMPC phosphate group; Development of a method of estimating the affinity of polyphenols for cell membranes.

Examines the regional and cellular expression of cystathionine β-synthase (CBS) in the developing and adult mouse central nervous system to elucidate the role of CBS in the nervous system. Effect of CBS deficiency on the normal development of brain; CBS expression in the radial glia/astrocyte lineage in the adult and developing mouse brain; CBS expression after kainic acid-induced seizures which represent an animal model for human temporal lobe epilepsy.

The effects of B2O3 doping on the microwave dielectric properties of a MgO compound were characterized in this study. The MgO and Mg3B2O6 compounds were recognized in the XRPD profiles of xMgO–(1 - x)B2O3 ceramics at a sintering temperature of 1350 °C for 4 h in a covered crucible. From the calculation of weight fraction of the compounds, the slight deviation in the concentrations of B2O3 and MgO from the stoichiometric composition of xMgO–(1 - x)B2O3 ceramics was also observed, and was attributed to the vaporization of B2O3 and the decomposition of Mg3B2O6 compound during the sintering. In the composition range of 0.95–0.99, abnormal grain growth of xMgO–(1 - x)B2O3 ceramics was observed; therefore, the decomposition of Mg3B2O6 compound into liquid phase and MgO compound may play an important role in enhancing the grain growth of the ceramics. The dielectric constant of xMgO–(1 - x)B2O3 ceramics ranged from 6.9 to 9.4 depending on the amount of Mg3B2O6 and MgO compounds, whereas the remarkable variation in the Q· f value of the ceramics was observed at x > 0.95. As a result, a maximum Q· f value of approximately 773000 GHz was obtained at x = 0.99. Such the variation in the Q· f value may be attributed to the sinterability of MgO compound, which is related to microstructural changes in the ceramics. [ABSTRACT FROM AUTHOR]

Although ovarian endometrioid carcinoma (OEC), frequently associated with endometrial endometrioid carcinoma (EEC), is often diagnosed at an early stage, the prognosis remains poor. The development of new, effective drugs to target these cancers is highly desirable. The bromodomain and extra-terminal domain (BET) family proteins serve a role in regulating transcription by recognizing histone acetylation, which is implicated in several types of cancer. BET inhibitors have been reported as promising cancer drugs. The present study aimed to assess the role of JQ1, a BET inhibitor, in ovarian and endometrial cancers. The sensitivity of OEC and EEC cell lines to JQ1 was assessed using cell viability and colony formation assays. Additionally, western blotting and cell cycle assays were performed to evaluate changes in c-Myc expression and apoptosis markers. Cell proliferation and colony formation assays revealed significant tumor suppression in both OEC and EEC cell lines in response to JQ1 treatment. Furthermore, treatment with JQ1 induced a decrease in c-Myc expression and an increase in apoptosis markers, such as cleaved PARP and the cell population in the sub-G1 phase, in both OEC and EEC cell lines. The findings of the present study indicate that JQ1 may induce cell death through c-Myc inhibition and could be a potentially novel therapeutic agent in the treatment in OEC and EEC. However, the direct mechanism, has not been fully elucidated, warranting further investigation., Competing Interests: KO was supported by grants from Daiichi Sankyo Co., Ltd. and AstraZeneca plc, and lecture fees from Chugai Pharmaceutical Co., Ltd. and AstraZeneca plc. All other authors declare that they have no competing interests., (Copyright: © 2024 Tanimoto et al.)