BMC Molecular and Cell Biology

Transcriptome and DNA methylation profiling during the NSN to SN transition in mouse oocytes
Demond H, Khan S, Castillo-Fernandez J, Hanna CW and Kelsey G
During the latter stages of their development, mammalian oocytes under dramatic chromatin reconfiguration, transitioning from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) stage, and concomitant transcriptional silencing. Although the NSN-SN transition is known to be essential for developmental competence of the oocyte, less is known about the accompanying molecular changes. Here we examine the changes in the transcriptome and DNA methylation during the NSN to SN transition in mouse oocytes.
BRAF regulates circPSD3/miR-526b/RAP2A axis to hinder papillary thyroid carcinoma progression
Li C, Zhao X, Zhao J, Zhao J, An L and Wu G
Papillary thyroid carcinoma (PTC) is a common malignant tumor. BRAF mutation has become a common molecular event in PTC pathogenesis. Circular RNA PSD3 (circPSD3) is known to be highly expressed in PTC. However, the bio-functional role of circPSD3 and its possible relationship with the BRAF in PTC is not clear. This study aims to probe the biofunction and molecular mechanism of circPSD3 in PTC pathogenesis.
Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome
Chen M, Sun D, Yee SP, Yuan Z, Lin L, Cui B, Wang Y, Liu C and Liu P
Inactivation or mutations of FAM20C causes human Raine Syndrome, which manifests as lethal osteosclerosis bone dysplasia or non-lethal hypophosphatemia rickets. However, it is only hypophosphatemia rickets that was reported in the mice with Fam20c deletion or mutations. To further investigate the local and global impacts of Fam20c mutation, we constructed a knock-in allele carrying Fam20c mutation (D446N) found in the non-lethal Raine Syndrome. The Fam20c allele replaced the WT Fam20c by 3.6Kb Col1a1-Cre to get the conditional knock-in mice, and by Hprt-cre to get conventional knock-in mice, respectively.
Functional significance of some common oxytocin receptor SNPs involved in complex human traits
Ma SL, Bowen MT and Dadds MR
Oxytocin function is associated with a range of human traits and is often indexed by common polymorphisms of the receptor gene OXTR. Little is known however about the functional significance of these polymorphisms.
Transient activation of YAP/TAZ confers resistance to morusin-induced apoptosis
Lee H, Cho SW, Cha HS, Tae K and Choi CY
The Hippo signaling pathway involves a kinase cascade that controls phosphorylation of the effector proteins YAP and TAZ, leading to regulation of cell growth, tissue homeostasis, and apoptosis. Morusin, a compound extracted from Morus alba, has shown potential in cancer therapy by targeting multiple signaling pathways, including the PI3K/Akt/mTOR, JAK/STAT, MAPK/ERK, and apoptosis pathways. This study explores the effects of morusin on YAP activation and its implications for apoptosis resistance.
The proneural transcription factor Atoh1 promotes odontogenic differentiation in human dental pulp stem cells (DPSCs)
Sabatini C, Lin HJ, Ovik G, Hall R and Lee T
Bioengineering of human teeth for replacement is an appealing regenerative approach in the era of gene therapy. Developmentally regulated transcription factors hold promise in the quest because these transcriptional regulators constitute the gene regulatory networks driving cell fate determination. Atonal homolog 1 (Atoh1) is a transcription factor of the basic helix-loop-helix (bHLH) family essential for neurogenesis in the cerebellum, auditory hair cell differentiation, and intestinal stem cell specification. The functional versatility of Atoh1 prompted us to test the possibility that Atoh1 may intersect the dental pulp stem cell (DPSC) gene regulatory network governing odontogenic differentiation.
Method for determining of cytotoxicity based on the release of fluorescent proteins
Lifanov D, Zorigt D, Shabalina E, Khalil A, Gorbunov K and Petersen E
This paper describes a method for determining the cytotoxicity of chemical compounds based on the detection of fluorescent proteins-in this case, green fluorescent protein (GFP) and red fluorescent protein (RFP), which are released into the medium from dead cells. This method is similar in principle to the lactate dehydrogenase test (LDH test), but it does not require a reaction with a chromogenic substrate. This method also makes it possible to independently determine the viability of different lines when used in cocultures. Experiments were performed on a classical monolayer, spheroids and 3D cultures in alginate hydrogel. Capecitabine was used as a model cytotoxic agent. We included liver cells (Huh7) in a coculture model and determined changes in the cytotoxicity levels of capecitabine against NCI-H1299 cells. The experimental part also found that there were differences in sensitivity to capecitabine depending on the type of 3D cultures used.
Designing multi-epitope vaccines against Echinococcus granulosus: an in-silico study using immuno-informatics
Khan J, Sadiq A, Alrashed MM, Basharat N, Hassan Mohani SNU, Shah TA, Attia KA, Shah AA, Khan H, Ali I and Mohammed AA
Cystic echinococcosis (CE) is a worldwide zoonotic public health issue. The reasons for this include a lack of specific therapy options, increasing antiparasitic drug resistance, a lack of control strategies, and the absence of an approved vaccine. The aim of the current study is to develop a multiepitope vaccine against CE by in-silico identification and using different Antigen B subunits. The five Echinococcus granulosus antigen B (EgAgB) subunits were examined for eminent antigenic epitopes, and then the best B-cell and Major Histocompatibility Complex MHC-binding epitopes were predicted. Most significant epitopes were combined to create an effective multi-epitope vaccine, which was then validated by testing its secondary and tertiary structures, physicochemical properties, and molecular dynamics (MD) modelling. A multi-epitope vaccine construct of 483 amino acid sequences was designed. It contains B-cell, Helper T Lymphocyte (HTL), and Cytotoxic T Lymphocyte (CTL) epitopes as well as the appropriate adjuvant and linker molecules. The resultant vaccinal construct had a GDT-HA value of 0.9725, RMSD of 0.299, MolProbity of 1.891, Clash score of 13.1, Poor rotamers of 0.9, and qualifying features with Rama favoured of 89.9. It was also highly immunogenic and less allergic. The majority of the amino acids were positioned in the Ramachandran plot's favourable area, and during the molecular dynamic simulation at 100 ns, no notable structural abnormalities were noticed. The resultant construct was significantly expressed and received good endorsement in the pIB2-SEC13-mEGFP expressional vector. In conclusion, the current in-silico multi-epitope vaccine may be evaluated in-vitro, in-vivo, and in clinical trials as an immunogenic vaccine model. It can also play a vital role in preventing this zoonotic parasite infection.
Convergent evolution of type I antifreeze proteins from four different progenitors in response to global cooling
Graham LA and Davies PL
Alanine-rich, alpha-helical type I antifreeze proteins (AFPs) in fishes are thought to have arisen independently in the last 30 Ma on at least four occasions. This hypothesis has recently been proven for flounder and sculpin AFPs, which both originated by gene duplication and divergence followed by substantial gene copy number expansion. Here, we examined the origins of the cunner (wrasse) and snailfish (liparid) AFPs. The cunner AFP has arisen by a similar route from the duplication and divergence of a GIMAP gene. The coding region for this AFP stems from an alanine-rich region flanking the GTPase domain of GIMAPa. The AFP gene has remained in the GIMAP gene locus and has undergone amplification there along with the GIMAPa gene. The AFP gene originated after the cunner diverged from its common ancestor with the closely related spotty and ballan wrasses, which exhibit similar gene synteny but lack AFP genes. Snailfish AFPs have also recently evolved because they are confined to a single genus of this family. In these AFP-producing species, the AFP locus does not share any similarity to functional genes. Instead, it is replete with repetitive DNAs and transposons, several stretches of which could encode alanine tracts with a dominant codon (GCC) that matches the bias observed in the AFP genes. All four known instances of type I AFPs occurring in fishes are independent evolutionary events that occurred soon after the onset of Northern Hemisphere Cenozoic glaciation events. Collectively, these results provide a remarkable example of convergent evolution to one AFP type.
Single-cell RNA sequencing identifies the expression of hemoglobin in chondrocyte cell subpopulations in osteoarthritis
Zhang Z, He T, Gu H, Zhao Y, Tang S, Han K, Hu Y, Wang H and Yu H
In recent years, chondrocytes have been found to contain hemoglobin, which might be an alternative strategy for adapting to the hypoxic environment, while the potential mechanisms of that is still unclear. Here, we report the expression characteristics and potential associated pathways of hemoglobin in chondrocytes using single-cell RNA sequencing (scRNA-seq). We downloaded data of normal people and patients with osteoarthritis (OA) from the Gene Expression Omnibus (GEO) database and cells are unbiased clustered based on gene expression pattern. We determined the expression levels of hemoglobin in various chondrocyte subpopulations. Meanwhile, we further explored the difference in the enriched signaling pathways and the cell-cell interaction in chondrocytes of the hemoglobin high-expression and low-expression groups. Specifically, we found that SPP1 was closely associated with the expression of hemoglobin in OA progression. Our findings provide new insights into the distribution characteristics of hemoglobin in chondrocytes and provide potential clues to the underlying role of hemoglobin in OA and the mechanisms related to that, providing potential new ideas for the treatment of OA.
Correction: Glycogen Synthase Kinase-3 regulates IGFBP-1 gene transcription through the Thymine-rich Insulin Response Element
Finlay D, Patel S, Dickson LM, Shpiro N, Marquez R, Rhodes CJ and Sutherland C
LEP O-GlcNAcylation inactivates NF-κB pathway by suppressing LEP protein level and thus mediates cellular senescence and osteogenic differentiation in mouse mesenchymal stem cells
Zhang Z, Zhou C and Yu L
Cellular senescence is a key driver of decreased bone formation and osteoporosis. Leptin (LEP) has been implicated in cellular senescence and osteogenic differentiation. The aim of this study was to investigate the mechanisms by which LEP mediates cellular senescence and osteogenic differentiation.
Evaluation of antibacterial and anticancer properties of secondary metabolites isolated from soil Bacillus spp focusing on two strains of Bacillus licheniformis and Bacillus siamensis
Shahniani A, Bamzadeh Z, Mahmoudnia F and Rouhi L
Bacillus strains are well recognized for their inherent production of bioactive compounds that exhibit antibacterial and anticancer properties. This study aims to evaluate the antimicrobial and anticancer effects of the secondary metabolite isolated from Bacillus licheniformis and Bacillus siamensis strain.
Neuroprotective effect of ciclopirox olamine in retinal ischemia/reperfusion injury
Du E, Jia X, Li X, Zhang B, Zhai Y and Qin F
Retinal ischemia-reperfusion (IR) injury is a basic pathological procedure in clinic and associated with various ischemic retinal diseases, including glaucoma, diabetic retinopathy, retinal vascular occlusion, etc. The purpose of this work is to investigate the effect of ciclopirox olamine (CPX) on retinal IR injury and further explore the underlying mechanism. In vitro assay exhibited that CPX exhibited significant neuroprotection against oxygen glucose deprivation (OGD) and oxidative stress-induced injuries in 661W photoreceptor cells. OGD injury showed a proinflammatory phenotype characterized by significantly increased production of cytokines (IL-6, IL-23 and TNF-α), while CPX significantly inhibited their secretion. In addition, the in vivo experiment demonstrated that CPX significantly preserved the normal thickness of the retina. Therefore, we suggest that CPX is identified in our research as a prospective therapeutic agent for retinal IR injury.
Induction of chronic asthma up regulated the transcription of senile factors in male rats
Hassanzadeh-Khanmiri M, Keyhanmanesh R, Mosaddeghi-Heris R, Delkhosh A, Rezaie J, Taghizadeh S, Sara MRS and Ahmadi M
The main characteristic of asthma is chronic inflammation. We examined cellular senescence by histology and molecular assay in the lungs of a rat model of asthma. This model comprises sensitization by several intraperitoneal injections of ovalbumin with aluminium hydroxide, followed by aerosol challenges every other day.
Role of layilin in regulating mitochondria-mediated apoptosis: a study on B cell lymphoma (BCL)-2 family proteins
Arito M, Tsutiya A, Sato M, Omoteyama K, Sato T, Motonaga Y, Suematsu N, Kurokawa MS and Kato T
Malignant gliomas exhibit rapid tumor progression and resistance to treatment, leading to high lethality. One of the causes is the reduced progression of apoptosis in glioma cells. Layilin is a type 1 transmembrane protein with a C-type lectin motif in its extracellular domain. We previously reported that layilin is mainly localized to mitochondria or their close proximity and that layilin is essential for maintaining of the fragmented type of mitochondria. This study investigates the effects of layilin on mitochondria-mediated apoptosis, focusing on B cell lymphoma (BCL)-2 family proteins in a glioma cell line of A172 cells.
Optimisation of cryopreservation conditions, including storage duration and revival methods, for the viability of human primary cells
Mohamed HM, Sundar P, Ridwan NAA, Cheong AJ, Mohamad Salleh NA, Sulaiman N, Mh Busra F and Maarof M
Cryopreservation is a crucial procedure for safeguarding cells or other biological constructs, showcasing considerable potential for applications in tissue engineering and regenerative medicine.
Differential methylation patterns in paternally imprinted gene promoter regions in sperm from hepatitis B virus infected individuals
Wu B, Sheng Y, Yu W, Ruan L, Geng H, Xu C, Wang C, Tang D, Lv M, Hua R and Li K
Hepatitis B virus (HBV) infection poses a substantial threat to human health, impacting not only infected individuals but also potentially exerting adverse effects on the health of their offspring. The underlying mechanisms driving this phenomenon remain elusive. This study aims to shed light on this issue by examining alterations in paternally imprinted genes within sperm.
Circulating microRNAs as potential biomarkers of physical activity in geriatric patients with HCV
Al-Rawaf HA, Gabr SA, Iqbal A and Alghadir AH
Circulating microRNAs have been implicated in a diverse array of biological and pathological phenomena. Their potential utility as noninvasive biomarkers for screening and diagnosing various diseases has been proposed.
Correction: The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts
Venugopal N, Ghosh A, Gala H, Aloysius A, Vyas N and Dhawan J
Upregulated dual oxidase 1-induced oxidative stress and caspase-1-dependent pyroptosis reflect the etiologies of heart failure
Li YS, Xia J, Chen CY, Ren SH and He MR
Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure.