Control Of Cell Differentiation Research Articles

COMMD5 counteracts cisplatin-induced nephrotoxicity by maintaining tubular epithelial integrity and autophagy flux.

Oxidative stress mediated by reactive oxygen species (ROS) contributes to apoptosis of tubular epithelial cells (TECs) and renal inflammation during acute kidney injury (AKI). Copper metabolism MURR1 domain-containing 5 [COMMD5/hypertension-related, calcium-regulated gene (HCaRG)] shows strong cytoprotective properties. COMMD5 is highly expressed in proximal tubules (PTs), where it controls cell differentiation. We assessed its role in cisplatin-induced AKI using transgenic mice in which COMMD5 is overexpressed in the PTs. Cisplatin caused the accumulation of damaged mitochondria and cellular waste in PTs, thus increasing the apoptosis of TECs. COMMD5 overexpression effectively protected TECs from cisplatin nephrotoxicity by decreasing intracellular ROS levels, mitochondrial dysfunction, and apoptosis through the preservation of tubular epithelial integrity, thus alleviating morphological and functional kidney damage. Excessive ROS production by hydrogen peroxide led to long-term autophagy activation through an increased burden on the autophagy/lysosome degradation system in TECs, and autophagic elimination of damaged mitochondria and cellular waste was compromised. COMMD5 attenuated oxidative injury by increasing autophagy flux, possibly due to a reduction of intracellular ROS levels through maintained tubular epithelial integrity, which decreased JNK/caspase-3-dependent apoptosis. Meanwhile, COMMD5 inhibition by siRNA reduced the resistance of TECs to cisplatin cytotoxicity, as shown by disrupted tubular epithelial integrity and cell viability. These data indicated that COMMD5 protects TECs from drug-induced oxidative stress and toxicity by maintaining tubular epithelial integrity and autophagy flux and ultimately decreases mitochondrial dysfunction and apoptosis. Increasing COMMD5 content in PTs is proposed as a new protective and therapeutic strategy against AKI.NEW & NOTEWORTHY Oxidative stress overload by drug treatment causes the accumulation of damaged mitochondria that could contribute to tubulopathy. However, effective preventive treatment for drug-induced acute kidney injury remains incompletely understood. Our study showed that copper metabolism MURR1 domain-containing 5 (COMMD5) reduced mitochondrial dysfunction and increased autophagy flux by alleviating reactive oxygen species production through maintaining tubular epithelial integrity when tubular epithelial cells were under oxidative stress, thus ameliorating renal function in cisplatin-treated mice. These results uncover a novel renoprotective mechanism underlying tubular epithelial integrity and autophagy flux.

Adaxial-abaxial bipolar leaf genes encode a putative cytokinin receptor and HD-Zip III, and control the formation of ectopic shoot meristems in rice.

Shoot apical meristems (SAMs) continuously initiate organ formation and maintain pluripotency through dynamic genetic regulations and cell-to-cell communications. The activity of meristems directly affects the plant's structure by determining the number and arrangement of organs and tissues. We have taken a forward genetic approach to dissect the genetic pathway that controls cell differentiation around the SAM. The rice mutants, adaxial-abaxial bipolar leaf 1 and 2 (abl1 and abl2), produce an ectopic leaf that is fused back-to-back with the fourth leaf, the first leaf produced after embryogenesis. The abaxial-abaxial fusion is associated with the formation of an ectopic shoot meristem at the adaxial base of the fourth leaf primordium. We cloned the ABL1 and ABL2 genes of rice by mapping their chromosomal positions. ABL1 encodes OsHK6, a histidine kinase, and ABL2 encodes a transcription factor, OSHB3 (Class III homeodomain leucine zipper). Expression analyses of these mutant genes as well as OSH1, a rice ortholog of the Arabidopsis STM gene, unveiled a regulatory circuit that controls the formation of an ectopic meristem near the SAM at germination.

The Association between Long Non-Coding RNAs and Alzheimer's Disease.

Neurodegeneration occurs naturally as humans age, but the presence of additional pathogenic mechanisms yields harmful and consequential effects on the brain. Alzheimer's disease (AD), the most common form of dementia, is a composite of such factors. Despite extensive research to identify the exact causes of AD, therapeutic approaches for treating the disease continue to be ineffective, indicating important gaps in our understanding of disease mechanisms. Long non-coding RNAs (lncRNAs) are an endogenous class of regulatory RNA transcripts longer than 200 nucleotides, involved in various regulatory networks, whose dysregulation is evident in several neural and extraneural diseases. LncRNAs are ubiquitously expressed across all tissues with a wide range of functions, including controlling cell differentiation and development, responding to environmental stimuli, and other physiological processes. Several lncRNAs have been identified as potential contributors in worsening neurodegeneration due to altered regulation during abnormal pathological conditions. Within neurological disease, lncRNAs are prime candidates for use as biomarkers and pharmacological targets. Gender-associated lncRNA expression is altered in a gender-dependent manner for AD, suggesting more research needs to be focused on this relationship. Overall, research on lncRNAs and their connection to neurodegenerative disease is growing exponentially, as commercial enterprises are already designing and employing RNA therapeutics. In this review we offer a comprehensive overview of the current state of knowledge on the role of lncRNAs in AD and discuss the potential implications of lncRNA as potential therapeutic targets and diagnostic biomarkers in patients with Alzheimer's disease.

Isoforms of the Cytoskeletal LIM-Domain Protein Zyxin in the Early Embryogenesis of Xenopus laevis

Objective: The study of highly conserved mechanosensitive proteins, such as zyxin, is essential due to their role in shaping embryos of all animals during embryogenesis through coordinated morphogenetic processes and controlled cell differentiation. This study aims to identify endogenous zyxin isoforms in Xenopus laevis and investigate changes in their abundance and intracellular localization during embryogenesis. Methods: Endogenous proteins were primarily detected using specific antibodies. Polyclonal antibodies targeting the C-terminal region of zyxin containing the NES and three LIM domains (438–663 aa), as well as antibodies against the N-terminal proline-rich region of Zyxin (1–373 aa) crucial for interactions with actinin and cytoskeletal proteins, were employed. Western blotting with these antibodies was conducted on Xenopus laevis embryo cell samples after fractionation into nuclear and cytoplasmic fractions. Results and Discussion: The study revealed multiple isoforms of zyxin in Xenopus laevis, including a full-length modified protein (105 kDa), an unmodified form (70 kDa), and two truncated forms of 45 and 37 kDa. The number and subcellular distribution of the truncated forms were found to vary based on the developmental stage, with increased levels of the 45 and 37 kDa isoforms observed in the early stages. Conclusions: This work provides novel insights into changes in the abundance and localization of zyxin isoforms during embryonic development, shedding light on the dynamics of this mechanosensitive protein in the embryo.

MEF2D Functions as a Tumor Suppressor in Breast Cancer.

The myocyte enhancer factor 2 (MEF2) gene family play fundamental roles in the genetic programs that control cell differentiation, morphogenesis, proliferation, and survival in a wide range of cell types. More recently, these genes have also been implicated as drivers of carcinogenesis, by acting as oncogenes or tumor suppressors depending on the biological context. Nonetheless, the molecular programs they regulate and their roles in tumor development and progression remain incompletely understood. The present study evaluated whether the MEF2D transcription factor functions as a tumor suppressor in breast cancer. The knockout of the MEF2D gene in mouse mammary epithelial cells resulted in phenotypic changes characteristic of neoplastic transformation. These changes included enhanced cell proliferation, a loss of contact inhibition, and anchorage-independent growth in soft agar, as well as the capacity for tumor development in mice. Mechanistically, the knockout of MEF2D induced the epithelial-to-mesenchymal transition (EMT) and activated several oncogenic signaling pathways, including AKT, ERK, and Hippo-YAP. Correspondingly, a reduced expression of MEF2D was observed in human triple-negative breast cancer cell lines, and a low MEF2D expression in tissue samples was found to be correlated with a worse overall survival and relapse-free survival in breast cancer patients. MEF2D may, thus, be a putative tumor suppressor, acting through selective gene regulatory programs that have clinical and therapeutic significance.

NSUN5 is essential for proper cell proliferation and differentiation of mouse preimplantation embryos.

Proper early embryonic development in mammals relies on precise cellular signaling pathways. This study reveals that NSUN5 is crucial for the regulation of the Hippo pathway, ensuring normal proliferation and differentiation in mouse preimplantation embryos. NOL1/NOP2/Sun domain family, member 5 (NSUN5) is an enzyme belonging to the 5-methylcytosine (m5C) writer family that modifies rRNA and mRNA. Our data revealed an upregulation of Nsun5 at the two-cell stage of mouse preimplantation development, suggesting its significance in early embryonic development. Given m5C's important role in stabilizing rRNA and mRNA and the Hippo signaling pathway's critical function in lineage segregation during embryogenesis, we hypothesized that NSUN5 controls cell differentiation by regulating the expression of components of the Hippo signaling pathway in mouse early embryos. To examine this hypothesis, we employed Nsun5-specific small interfering RNAs for targeted gene silencing in mouse preimplantation embryos. Nsun5 knockdown resulted in significant developmental impairments including reduced blastocyst formation, smaller size of blastocysts, and impaired hatching from the zona pellucida. Nsun5 knockdown also led to decreased cell numbers and increased apoptosis in embryos. We also observed diminished nuclear translocation of yes-associated protein 1 (YAP1) in Nsun5 knockdown embryos at the morula stage, indicating disrupted cell differentiation. This disruption was further evidenced by an altered ratio of CDX2-positive to OCT4-positive cells. Furthermore, Nsun5 depletion was found to upregulate the Hippo signaling-related key genes, Lats1 and Lats2 at the morula stage. Our findings underscore the essential role of Nsun5 in early embryonic development by affecting cell proliferation, YAP1 nuclear translocation, and the Hippo pathway.

Multiple Roles of Brassinosteroid Signaling in Vascular Development.

Brassinosteroids (BRs) are plant steroid hormones that control growth and stress responses. In the context of development, BRs play diverse roles in controlling cell differentiation and tissue patterning. The vascular system, which is essential for transporting water and nutrients throughout the plant body, initially establishes a tissue pattern during primary development and then dramatically increases the number of vascular cells during secondary development. This complex developmental process is properly regulated by a network consisting of various hormonal signaling pathways. Genetic studies have revealed that mutants that are defective in BR biosynthesis or the BR signaling cascade exhibit a multifaceted vascular development phenotype. Furthermore, BR crosstalk with other plant hormones, including peptide hormones, coordinately regulates vascular development. Recently, the involvement of BR in vascular development, especially in xylem differentiation, has also been suggested in plant species other than the model plant Arabidopsis thaliana. In this review, we briefly summarize the recent findings on the roles of BR in primary and secondary vascular development in Arabidopsis and other species.

Wnt dose escalation during the exit from pluripotency identifies tranilast as a regulator of cardiac mesoderm

Wnt signaling is a critical determinant of cell lineage development. This study used Wnt dose-dependent induction programs to gain insights into molecular regulation of stem cell differentiation. We performed single-cell RNA sequencing of hiPSCs responding to a dose escalation protocol with Wnt agonist CHIR-99021 during the exit from pluripotency to identify cell types and genetic activity driven by Wnt stimulation. Results of activated gene sets and cell types were used to build a multiple regression model that predicts the efficiency of cardiomyocyte differentiation. Cross-referencing Wnt-associated gene expression profiles to the Connectivity Map database, we identified the small-molecule drug, tranilast. We found that tranilast synergistically activates Wnt signaling to promote cardiac lineage differentiation, which we validate by invitro analysis of hiPSC differentiation and invivo analysis of developing quail embryos. Our study provides an integrated workflow that links experimental datasets, prediction models, and small-molecule databases to identify drug-like compounds that control cell differentiation.

Pan-cellular organelles and suborganelles-from common functions to cellular diversity?

Cell diversification is at the base of increasing multicellular organism complexity in phylogeny achieved during ontogeny. However, there are also functions common to all cells, such as cell division, cell migration, translation, endocytosis, exocytosis, etc. Here we revisit the organelles involved in such common functions, reviewing recent evidence of unexpected differences of proteins at these organelles. For instance, centrosomes or mitochondria differ significantly in their protein composition in different, sometimes closely related, cell types. This has relevance for development and disease. Particularly striking is the high amount and diversity of RNA-binding proteins at these and other organelles, which brings us to review the evidence for RNA at different organelles and suborganelles. We include a discussion about (sub)organelles involved in translation, such as the nucleolus and ribosomes, for which unexpected cell type-specific diversity has also been reported. We propose here that the heterogeneity of these organelles and compartments represents a novel mechanism for regulating cell diversity. One reason is that protein functions can be multiplied by their different contributions in distinct organelles, as also exemplified by proteins with moonlighting function. The specialized organelles still perform pan-cellular functions but in a cell type-specific mode, as discussed here for centrosomes, mitochondria, vesicles, and other organelles. These can serve as regulatory hubs for the storage and transport of specific and functionally important regulators. In this way, they can control cell differentiation, plasticity, and survival. We further include examples highlighting the relevance for disease and propose to examine organelles in many more cell types for their possible differences with functional relevance.

Unveiling the topographic cue rendered by micropatterns for steering cell differentiation by using extrinsic photobiomodulation

It is known that cell culture micropatterns have the ability to facilitate stem cell differentiation induced by specialized chemical factors and different differentiation directions have different optimal micropattern shapes. In this study, by utilizing extrinsic photobiomodulation (EPM) with verteporfin as photosensitizer and light irradiation of 690 nm wavelength as a universal, unbiased, and synchronizing way of inducing differentiation of human umbilical cord Wharton's Jelly mesenchymal stem cells (WJ-MSCs), the topographic cue for cell type specification conveyed in microislands is investigated. It is found that the topographic cues are encoded in the symmetry and aspect ratio of microislands and conformation of cells to microislands is necessary for acquiring the cue. F-actin vertical columns form and cell thickness increases for cells on microislands, and the two effects are enhanced by EPM and correlate with cell differentiation. EPM treatment poises cells in a stationary state to initiate differentiation and the process of making commitment takes two days. Our findings reveal the way to fully exploit topographic cues for promoting and controlling cell differentiation.

Ubiquitin E3 Ligase FBXO9 Regulates Pluripotency by Targeting DPPA5 for Ubiquitylation and Degradation.

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have unique characteristics where they can both contribute to all three germ layers in vivo and self-renewal indefinitely in vitro. Post-translational modifications of proteins, particularly by the ubiquitin proteasome system (UPS), control cell pluripotency, self-renewal, and differentiation. A significant number of UPS members (mainly ubiquitin ligases) regulate pluripotency and influence ESC differentiation with key elements of the ESC pluripotency network (including the "master" regulators NANOG and OCT4) being controlled by ubiquitination. To further understand the role of the UPS in pluripotency, we performed an RNAi screen during induction of cellular reprogramming and have identified FBXO9 as a novel regulator of pluripotency associated protein DPPA5. Our findings indicate that FBXO9 silencing facilitates the induction of pluripotency through decreased proteasomal degradation of DPPA5. These findings identify FBXO9 as a key regulator of pluripotency.

Influences of probiotics and gut microbiota on immunomodulation for the treatment of patients with cancer: a systematic review

Introduction: Immunomodulation and immunostimulation are the main mechanisms of action of probiotics in the fight against cancer. Objective: It was to carry out a systematic review of the influences of probiotics and gut microbiota on immunomodulation for the treatment of cancer patients. Methods: The PRISMA Platform systematic review rules were followed. The research was carried out from September to October 2023 in the Web of Science, Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 125 articles were found, and 35 articles were evaluated in full and 18 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 45 studies with a high risk of bias and 15 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=55.4%>50%. It was concluded that probiotics suppress inflammation by inhibiting several signaling pathways and reducing the global activation of NF-κβ and the production of pro-inflammatory cytokines. Probiotics influence receptor antagonism, receptor expression, binding and expression of adapter proteins, expression of negative regulatory signal molecules, and mainly the induction of microRNAs. These microRNAs can modulate the gene expression of tumor cells together with regulatory T cells that have important functions in the tumor microenvironment, mainly in inducing immune evasion. Some modulatory effects of probiotics include the production of cytokines by epithelial cells, increased mucin secretion and phagocytosis and NK cell activity, activation of T and NKT cells, stimulation of IgA production, and decreased proliferation of T cells. The gut microbiota has a major impact on the systemic immune system. The specific microbiota controls cell differentiation in which CD4+ T cells (Th17 cells) secrete IL-17. The presence of Th17 cells and regulatory T cells is associated with the gut microbiota.

Lipid peroxidation of immune cells in cancer.

Growing evidence indicates that cellular metabolism is a critical determinant of immune cell viability and function in antitumor immunity and lipid metabolism is important for immune cell activation and adaptation to the tumor microenvironment (TME). Lipid peroxidation is a process in which oxidants attack lipid-containing carbon-carbon double bonds and is an important part of lipid metabolism. In the past decades, studies have shown that lipid peroxidation participates in signal transduction to control cell proliferation, differentiation, and cell death, which is essential for cell function execution and human health. More importantly, recent studies have shown that lipid peroxidation affects immune cell function to modulate tumor immunity and antitumor ability. In this review, we briefly overview the effect of lipid peroxidation on the adaptive and innate immune cell activation and function in TME and discuss the effectiveness and sensitivity of the antitumor ability of immune cells by regulating lipid peroxidation.

Mitochondrial metabolism in AML cells

Mitochondrial metabolic dependencies characteristic of acute myeloid leukemia (AML) have recently been identified, demonstrating that metabolic enzymes regulate AML gene expression and control cell differentiation and stemness. These mitochondrial metabolic adaptations occur independently of underlying genomic abnormalities and contribute to chemotherapy resistance and relapse. Mitochondrial alterations also lead to metabolic vulnerability of AML cells, whose metabolism is characterized by dependence on oxidative phosphorylation, fatty acid oxidation, reactive oxygen species (ROS) production, and mitochondrial dynamics. Currently, mitochondrial properties of AML cells and leukemia stem cells are being investigated, focusing on metabolism, signal transduction, mitochondrial respiration, ROS generation, and mitophagy. In addition, mitochondria-targeted agents have shown promising results in clinical trials. This paper outlines recent findings from preclinical and clinical trials on the utility of agents targeting mitochondria-related molecules and metabolic pathways and their efficacy in combination with existing chemotherapies.

Influence of Serum Ferritin and B12 Levels in the Functional Outcomes of Patients with Ruptured and Unruptured Intracranial Aneurysms

Abstract Introduction Pathological processes in the arterial wall that result in vessel dilation are the cause of intracranial aneurysms (IAs), and the risk factors for their formation and progression are not well established. Ferritin is associated with inflammation and angiogenesis; it has protective antioxidative activity, and controls cell differentiation. Vitamin B12 is related to neurological and hematological disorders; it can be used as differential diagnosis tool, and acts in the control of homocysteinemia, a predictor of worse prognosis. The present article aims to assess the correlation between serum ferritin and B12 levels and the patient's functional outcome. Materials and Methods In the present cohort study, we assessed the serum levels of ferritin and B12, as well as the scores on the modified Rankin and Glasgow Outcome Scales at 6 months, of 2 groups, one with 19 and the other with 49 individuals, out of 401 patients treated for IA at Universidade de São Paulo from 2018 to 2019. We performed a statistical analysis, using logistic regression, to determine the aforementioned correlation. Results In the univariable analysis, the serum levels of ferritin showed no significant impact on the functional outcome (odds ratio [OR]: 0.96 for every 100 pg/mL increase; 95% confidence interval [95%CI]: 0.761–1.210; p = 0.732); neither did the serum levels of B12 (OR: 0.998 for every 100 pg/mL increase; 95%CI: 0.826–1.206; p = 0.987). Moreover, no significant impact on the functional outcome was observed in the multivariable analysis regarding the serum levels of B12, age, hypertension, and aneurysm rupture (OR: 1.086 for every 100 pg/mL increase; 95%CI: 0.847–1.392; p = 0.513). Conclusion We were not able to confirm a statistical correlation regarding the serum levels of ferritin and B12, and functional outcome of IA patients. These variables might be linked to other determinants of the pathophysiology of IAs, like inflammation and homocysteinemia.

New Insights into Hematopoietic Redefinition and New Paradigms in Hematopoietic Hierarchy Roadmap

The definition of hematopoietic progenitor cells (HPCs) has not been standardized. Surface markers are insufficient to capture the entire differentiation stages of progenitor cells and reflect the dynamic differentiation mechanisms underlying hematopoiesis. Deciphering the hematopoiesis mechanism that underlies progenitor cells definition and fate decision are critical to understanding fundamental questions of hematopoietic lineage commitment. Here, we redefined the entire spectrum of adult hematopoietic progenitors, and recovered the critical transcript factors (TFs) in lineages fate decision, and reaffirmed the lineage commitment model of HPCs by a comprehensive transcriptome. The progenitor lineages were accurately redefined with unique makers and transcription factors by unsupervised dimensionality reduction and clustering, which subverted the conventional definition of HPCs（Table 1）. The expression characteristics of TFs, such as GATA1, KLF1, PRDM1, and MAFB, presented enormous capacity to define the entire spectrum of HPCs. The transcriptional atlas showed that original hematopoietic progenitors were simultaneously primed into lymphoid, neutrophils, and megakaryocytic-erythroid progenitor cell types in the initial differentiation stage and thereafter matured into different hematopoietic lineages (Figure 1). The common intermediate progenitor stage was not observed among myeloid lineages, indicating the absence of a common myeloid progenitor during the lineage commitment. Our transcriptional atlas revealed the major fate decision factors in each branch among hematopoietic hierarchy formation (Table 1). Several fate decision factors were identified, including GATA2, TESPA1, and MYB of myeloid progenitors and HOXA9, HOPX, and TSC22D1 of lymphoid progenitors. Through the sequential activation/deactivation of TFs, synergism with key receptor genes, and signal activation, the original progenitor cells were primed and differentiated into various progenitors. The expression and activation characteristics of fate decision TFs faithfully reflect the mechanisms underlying hematopoietic lineage commitment. A hematopoietic hierarchy roadmap was reaffirmed. Our reaffirmed hematopoietic hierarchy validated that the megakaryocytic-erythroid lineage process is continuous, while the lymphoid lineage process is more likely a discrete stepwise progression with distinct lineage-committed populations during hematopoiesis, opening a new perspective on hematopoiesis (Figure 1). Our study revealed that the original progenitors of basophils, eosinophils, and neutrophils differed. Plasma progenitor cells were first identified and defined, and the rearrangements of IGHV, IGKV, and IGLV genes were already existed and occurred during the progenitor state of plasma cells. In summary, our transcriptional atlas of HPCs provides an accurate definition, hierarchy, and biological insights into hematopoiesis and lineage commitment. Our study opens up numerous possibilities for precise and controlled progenitor cell differentiation, facilitating research development in regenerative medicine and disease treatment.

Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis.

The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell-derived TNF as an upstream regulator of mucin homeostasis.

Manipulation of osteogenic and adipogenic differentiation of human degenerative disc and ligamentum flavum derived progenitor cells using IL-1β, IL-19, and IL-20.

To elucidate whether pro-inflammatory cytokines might influence the commitment of intervertebral disc (IVD)- and ligamentum flavum (LF)-derived progenitor cells toward either osteogenesis or adipogenesis, specifically Interleukin-1β (IL-1β), IL-19, and IL-20. Sixty patients with degenerative spondylolisthesis and lumbar or lumbosacral spinal stenosis were included in the study. Injuries to the spine, infections, and benign or malignant tumors were excluded. From nine patient samples, IVD- and LF-derived cells were isolated after primary culture, and two clinical samples were excluded due to mycoplasma infection. The effects of IL-1β, IL-19, as well as IL-20 in regulating osteogenic and adipogenic differentiation in vitro were investigated. Primary IVD- and LF-derived cells were found to have a similar cell morphology and profile of surface markers (CD44, CD90, and CD105) as placenta-derived mesenchymal stem cells (MSCs). Primary IVD/LF cells have a high capacity to differentiate into osteocytes and adipocytes. IL-19 had a tendency to promote adipogenesis. IL-20 inhibited osteogenesis and promoted adipogenesis; IL-1β promoted osteogenesis but inhibited adipogenesis. IL-1β, IL-19, and IL-20 impact the adipogenic and osteogenic differentiation of IVD-derived and LF-derived cells. Modulating the expression of IL-1β, IL-19, and IL-20 provides a potential avenue for controlling cell differentiation of IVD- and LF-derived cells, which might have beneficial effect for degenerative spondylolisthesis and spinal stenosis.

Emerging role of MicroRNA-Based theranostics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), with its high mortality and short survival rate, continues to be one of the deadliest malignancies despite relentless efforts and several technological advances. The poor prognosis of HCC and the few available treatments are to blame for the low survival rate, which emphasizes the importance of creating new, effective diagnostic markers and innovative therapy strategies. In-depth research is being done on the potent biomarker miRNAs, a special class of non-coding RNA and has shown encouraging results in the early identification and treatment of HCC in order to find more viable and successful therapeutics for the disease. It is beyond dispute that miRNAs control cell differentiation, proliferation, and survival and, depending on the genes they target, can either promote tumorigenesis or suppress it. Given the vital role miRNAs play in the biological system and their potential to serve as ground-breaking treatments for HCC, more study is required to fully examine their theranostic potential.

Contribution of metabolic abnormalities to acute myeloid leukemia pathogenesis.

Acute myeloid leukemia (AML) is a malignant disease of myeloid precursors. Somatic mutations have long been accepted as drivers of this malignancy. Over the past decade, unique mitochondrial and metabolic dependencies of AML and AML stem cells have been identified, including a reliance on oxidative phosphorylation. More recently, metabolic enzymes have demonstrated noncanonical roles in regulating gene expression in AML, controlling cell differentiation and stemness. These mitochondrial and metabolic adaptations occur independent of underlying genomic abnormalities and contribute to chemoresistance and relapse. In this opinion article, we discuss the current understanding of AML pathogenesis and whether mitochondrial and metabolic abnormalities drive leukemogenesis or are a non-contributory phenotype.