Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

Bioremediation of trichloroethylene-contaminated groundwater using green carbon-releasing substrate with pH control capability.

In this research, a sustainable substrate, termed green and long-lasting substrate (GLS), featuring a blend of emulsified substrate (ES) and modified rice husk ash (m-RHA) was devised. The primary objective was to facilitate the bioremediation of groundwater contaminated with trichloroethylene (TCE) using innovative GLS for slow carbon release and pH control. The GLS was concocted by homogenizing a mixture of soybean oil, surfactants (Simple Green™ and soya lecithin), and m-RHA, ensuring a gradual release of carbon sources. The hydrothermal synthesis was applied for the production of m-RHA production. The analyses demonstrate that m-RHA were uniform sphere-shape granules with diameters in micro-scale ranges. Results from the microcosm study show that approximately 83% of TCE could be removed (initial TCE concentration = 7.6 mg/L) with GLS supplement after 60 days of operation. Compared to other substrates without RHA addition, higher TCE removal efficiency was obtained, and higher Dehalococcoides sp. (DHC) population and hydA gene (hydrogen-producing gene) copy number were also detected in microcosms with GLS addition. Higher hydrogen concentrations enhanced the DHC growth, which corresponded to the increased DHC populations. The addition of the GLS could provide alkalinity at the initial stage to neutralize the acidified groundwater caused by the produced organic acids after substrate biodegradation, which was advantageous to DHC growth and TCE dechlorination. The addition of m-RHA reached an increased TCE removal efficiency, which was due to the fact that the m-RHA had the zeolite-like structure with a higher surface area and lower granular diameter, and thus, it resulted in a more effective initial adsorption effect. Therefore, a significant amount of TCE could be adsorbed onto the surface of m-RHA, which caused a rapid TCE removal through adsorption. The carbon substrates released from m-RHA could then enhance the subsequent dechlorination. The developed GLS is an environmentally-friendly and green substrate.

Blood biomarkers to distinguish complicated and uncomplicated appendicitis in pediatric patients.

BACKGROUND: /Purpose: Acute appendicitis (AA) stands as the most prevalent cause of acute abdominal pain among children. The potential for morbidity escalates significantly when uncomplicated appendicitis (UA) progresses to complicated appendicitis (CA), which can encompass gangrenous, necrotic, or perforated appendicitis. Consequently, establishing an early and accurate diagnosis of AA, and effectively differentiating CA from UA, becomes paramount. This study explores the diagnostic utility of various blood biomarkers for distinguishing CA from UA in pediatric patients. METHODS: We conducted a retrospective review of medical records pertaining to pediatric patients who underwent surgery for AA. Patients were categorized as either having UA or CA based on histopathological examination of the appendix. The data collected and analyzed included demographic information, white blood cell (WBC) count, neutrophil proportion, lymphocyte proportion, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels upon admission. RESULTS: Among the 192 pediatric patients who underwent surgery for AA, 150 were diagnosed with UA, while 42 were diagnosed with CA. The CA group exhibited significantly higher neutrophil proportions, NLRs, PLRs, and CRP levels, alongside lower lymphocyte proportions (all p < 0.01) compared to the UA group. Receiver operating characteristic (ROC) curve analysis disclosed that CRP exhibited the highest specificity, sensitivity, and positive and negative predictive values for predicting CA. CONCLUSION: CRP emerges as a valuable biomarker for differentiating complicated appendicitis from uncomplicated appendicitis.

The synergistic and enhancive effects of IL-6 and M-CSF to expand and differentiate functional dendritic cells from human monocytes under serum-free condition.

BACKGROUND: Dendritic cells (DCs) are differentiated from monocytes, and have a strong ability to perform phagocytosis, present antigens and activate T cell immune response. Therefore, DCs are one of the key factors in fighting cancer in immunotherapy, and it is an important issue to develop a serum-free system for DC differentiation and expansion in vitro for clinical application. RESULTS: In this study, IL-6 and M-CSF were determined and a concentration combination of cytokines was optimized to develop an optimal DC serum-free differentiation medium (SF-DC Optimal) that can effectively differentiate CD14+ monocytes into CD40+CD209+ DCs. After differentiation, the morphology, growth kinetics, surface antigen expression, phagocytosis ability, cytokine secretion, mixed lymphocyte reaction and stimulation for maturation of the differentiated DCs were checked and confirmed. Importantly, this research is the first report finding that the addition an extra low concentration of IL-6 and M-CSF exhibited a synergistic effect with GM-CSF and IL-4 to generate higher numbers and more fully functional DCs than the addition of GM-CSF and IL-4 only under serum-free condition. CONCLUSION: A large number of functional DCs can be generated by using SF-DC Optimal medium and provide an alternative source of DCs for related basic research and clinical applications.

Bioremediation potential of cadmium by recombinant Escherichia coli surface expressing metallothionein MTT5 from Tetrahymenathermophila.

Cadmium (Cd) is a common heavy metal contaminant in industrial wastewater that causes many diseases in humans. Metallothionein (MT), a cysteine-rich metal-binding protein, is well known in chelate-heavy metals. In this study, we expressed MTT5 of Tetrahymena thermophila fused with Lpp-OmpA in the outer membrane of Escherichia coli to determine its ability to accumulate and adsorb Cd. Our results revealed that our recombinant E. coli had a 4.9-fold greater Cd adsorption compared to wild E. coli. Adsorption isothermic analysis demonstrated that the adsorption behavior for Cd in our recombinant bacteria was better fitted into the Freundlich isotherm model than Langmuir isotherm model. Fourier-transform infrared spectroscopy indicated that phosphate and organic phosphate groups were involved in the interaction between Cd and the bacterial surface. Using quantitative reverse transcription polymerase chain reaction, we further showed that the expression of metal-resistance genes (dnaK and clpB) was downregulated due to surface MTT5 protected our recombinant bacteria from Cd2+ adsorption. Furthermore, we showed that our recombinant bacteria could adsorb Cd from the contaminated wastewater containing other metals and were suggested to be applied in the field study.

Blockage of Nrf2 and autophagy by L-selenocystine induces selective death in Nrf2-addicted colorectal cancer cells through p62-Keap-1-Nrf2 axis.

Persistent Nrf2 activation is typically noted in many cancers, including colorectal cancer (CRC), aiding cancer cells in overcoming growth stress and promoting cancer progression. Sustained Nrf2 activation, which is beneficial for cancer cells, is called "Nrf2 addiction"; it is closely associated with malignancy and poor prognosis in patients with cancer. However, Nrf2 inhibitors may have adverse effects on normal cells. Here, we found that the selenocompound L-selenocystine (SeC) is selectively cytotoxic in the Nrf2-addicted CRC cell line WiDr cells, but not in non-Nrf2-addicted mesenchymal stem cells (MSCs) and normal human colon cells. Another CRC cell line, C2BBe1, which harbored lower levels of Nrf2 and its downstream proteins were less sensitive to SeC, compared with the WiDr cells. We further demonstrated that SeC inhibited Nrf2 and autophagy activation in the CRC cells. Antioxidant GSH pretreatment partially rescued the CRC cells from SeC-induced cytotoxicity and Nrf2 and autophagy pathway inhibition. By contrast, SeC activated Nrf2 and autophagy pathway in non-Nrf2-addicted MSCs. Transfecting WiDr cells with Nrf2-targeting siRNA decreased persistent Nrf2 activation and alleviated SeC cytotoxicity. In KEAP1-knockdown C2BBe1 cells, Nrf2 pathway activation increased SeC sensitivity and cytotoxicity. In conclusion, SeC selectively attacks cancer cells with constitutively activated Nrf2 by reducing Nrf2 and autophagy pathway protein expression through the P62-Nrf2-antioxidant response element axis and eventually trigger cell death.

Toxicity determination, pollution source delineation, and microbial diversity evaluation of PAHs-contaminated sediments for an urban river.

The Feng-Sang River is a metropolitan river in Kaohsiung City, Taiwan. In this study, Feng-Sang River sediments were analyzed to investigate the distributions and sources of polycyclic aromatic hydrocarbons (PAHs). The Sediment Quality Guidelines (SQGs), potentially carcinogenic PAHs (TEQcarc ), and toxic equivalence quotient (TEQ) were applied to evaluate influences of PAHs on ecosystems and microbial diversities. Results indicate that PAHs concentrations varied between seasons and locations. The concentrations of ∑16 PAHs ranged from 73.6 to 603.8 ng/kg in dry seasons and from 2.3 to 199.3 ng/kg in wet seasons. This could be because of the flushing effect during wet seasons, which caused the movement and dilution of the PAH-contaminated sediments. Diagnostic ratio analysis infers that high PAHs levels were generated by combustion processes and vehicle traffic, and results from multivariate descriptive statistical analysis also demonstrate that the vehicular traffic pollution could be the major emission source of PAHs contamination. Comparisons of PAHs with SQGs indicate that PAHs concentrations in sediment were below the effects range low (ERL) values, and thus, the immediate threat to organisms might not be significant. The diagnostic ratio analyses are effective methods for PAH source appointment. The metagenomic assay results imply that sediments contained essential microbial species with eminent diversity. The detected PAH-degrading bacteria (Desulfatiglans, Dechloromonas, Sphingomonas, Methylobacterium, Rhodobacter, Clostridium, and Exiguobacterium) played a key role in PAHs biotransformation, and Dechloromonas and Rhodobacter had a higher relative abundance. Results of microbial diversity analyses indicate that the contaminated environment induced the changes of governing microbial groups in sediments. PRACTITIONER POINTS: Diagnostic ratio analyses are effective methods for PAHs source appointment. Microbial composition in sediments are highly affected by anthropogenic pollution. Combustion and vehicle traffic contribute to urban river sediments pollution by PAHs. Dechloromonas and Rhodobacter are dominant PAHs-degrading bacteria in sediments.

One step synthesis of 10B-enriched 10BPO4 nanoparticles for effective boron neutron capture therapeutic treatment of recurrent head-and-neck tumor.

Recurrent head-and-neck (H&N) cancer is one of the most malignant cancers in the world. Various treatment modalities, such as radiation therapy, chemotherapy, and surgery were adopted to treat H&N cancer, but recurrence of H&N tumor always occurs again, leading to poor prognosis and low 5-year survival rate. Recently, boron neutron capture therapy (BNCT) emerges an alternative modality for curing recurrent tumors. Presently, boron phenylalanine-fructose (BPA-F) and sodium borocaptate (BSH) are the two best BNCT molecular drugs, which, however, have poor therapeutic efficacies and are lack of tumor-targeting ability. In this study, 10B-riched (98.5% 10B) boron phosphate nanoparticles (10BPO4 NPs) of ∼100 nm in size were prepared in a single step using a unique microwave arcing method. The 10B-enriched 10BPO4 NPs were surface-modified with anti-EGFR antibody to endow the targeting ability toward H&N cancer cells. In in-vivo xenograft mice model, a large amount (∼63 µg 10B/g cancer cells) of 10B atoms could be effectively accumulated at the H&N tumor sites using 10BPO4 NPs as BNCT reagents. In in-vitro neutron irradiation experiments, 72% cell deaths were observed from anti-EGFR-10BPO4 NPs-treated H&N cancer cells, which is ∼2.4 folds higher than that (30%) treated with the most effective molecular drug, BPA-F. We demonstrated that upon neutron irradiation, the anti-EGFR-10BPO4 NPs could exert a much higher extent of destruction of H&N tumor, as well as effective suppression of the probability of H&N tumor recurrence, as compared to the most effective molecular drug, BPA-F. The median survival of the BNCT treated mice with anti-EGFR-10BPO4 NPs extends beyond 75 days, which is far better than the mice treated with BPA-F (33 days), blank + NR mice (25), and blank mice (23 days).

Construction of a Tandem Repeat Peptide Sequence with Pepsin Cutting Sites to Produce Recombinant α-Melanocyte-Stimulating Hormone.

The production of α-melanocyte-stimulating hormone (α-MSH), a peptide hormone composed of 13 amino acids, is attempted by recombinant expression using E. coli as the host. To achieve this aim, a synthetic gene containing eight tandem repeats of msh gene (8msh) was designed for ribosomal synthesis of 8 α-MSH. The merit of the strategy is to diminish the peptide toxicity against the host cell and to achieve a higher production yield. Pepsin cleavage sites are introduced between the peptides for enzymatic proteolysis to obtain the monomeric peptide of α-MSH. The constructed plasmid was transformed into different strains of E. coli hosts, and E. coli XL1-Blue with gene 8msh revealed the highest yield of 8 α-MSH. Although 8 α-MSH was fractionalized in the insoluble pellets after cell lysis, pepsin cleavage was able to produce soluble α-MSH peptide, as analyzed and confirmed by mass spectrometry and peptide activity assays. The production of α-MSH was quantified using HPLC with a yield of 42.9 mg/L of LB culture. This study demonstrates the feasibility of producing α-MSH using recombinant expression of tandem repeat gene. The production procedure involves minimal post-treatment and processing and can be scaled up for industrial application.

CCL2 associated with CD38 expression during ex vivo expansion in human cord blood-derived hematopoietic stem cells.

To date, different experimental strategies have been developed for the ex vivo expansion of human hematopoietic stem cells (HSCs) for clinical applications. However, differences in the genomic function of expanded HSCs under different culture systems remain unclear. In this study, we compared the gene expression profiles of HSCs in ex vivo expanded serum (10% FBS, fetal bovine serum) and serum-free culture systems and analyzed the molecular functions of differentially expressed genes using microarray chips. We identified 839 differentially expressed genes between the two culture systems. These genes were enriched in the TNF -regulated inflammatory pathway in an FBS culture system. In addition, the mRNA expression of CCL2 (C-C motif chemokine ligand 2), TNF (tumor necrosis factor) and FOS (FBJ murine osteosarcoma viral oncogene homolog) was validated by RT-qPCR. Our data revealed that ex vivo expansion of HSCs using the FBS culture system induces an inflammatory response and high CD38 expression, indicating that this system might activate an inflammatory pathway and induce expression of the cancer marker CD38 during ex vivo expansion of HSCs. This study provides a transcriptional profile and new insights into the genomic functions of HSCs under different expanded cultures.

Transcriptional regulation of lysophosphatidic acid receptors 2 and 3 regulates myeloid commitment of hematopoietic stem cells.

Lysophosphatidic acid (LPA) is one of the lipids identified to be involved in stem cell differentiation. It exerts various functions through activation of G protein-coupled lysophosphatidic acid receptors (LPARs). In previous studies, we have demonstrated that activation of LPA receptor 3 (LPA3) promotes erythropoiesis of human hematopoietic stem cells (HSCs) and zebrafish using molecular and pharmacological approaches. Our results show that treatment with lysophosphatidic acid receptor 2 (LPA2) agonist suppressed erythropoiesis, whereas activation of LPA3 by 1-oleoyl-2-methyl-sn-glycero-3-phosphothionate (2S-OMPT) promoted it, both in vitro and in vivo. Furthermore, we have demonstrated the inhibitory role of LPA3 during megakaryopoiesis. However, the mechanism underlying these observations remains elusive. In the present study, we suggest that the expression pattern of LPARs may be correlated with the transcriptional factors GATA-1 and GATA-2 at different stages of myeloid progenitors. We determined that manipulation of GATA factors affected the expression levels of LPA2 and LPA3 in K562 leukemia cells. Using luciferase assays, we demonstrate that the promoter regions of LPAR2 and LPAR3 genes were regulated by these GATA factors in HEK293T cells. Mutation of GATA-binding sites in these regions abrogated luciferase activity, suggesting that LPA2 and LPA3 are regulated by GATA factors. Moreover, physical interaction between GATA factors and the promoter region of LPAR genes was verified in K562 cells using chromatin immunoprecipitation (ChIP) studies. Taken together, our results suggest that balance between LPA2 and LPA3 expression, which may be determined by GATA factors, is a regulatory switch for lineage commitment in myeloid progenitors. The expression-level balance of LPA receptor subtypes represents a novel mechanism regulating erythropoiesis and megakaryopoiesis.

Lysophosphatidic acid receptors 2 and 3 regulate erythropoiesis at different hematopoietic stages.

Hematopoiesis, the complex developmental process that forms blood components and replenishes the blood system, involves multiple intracellular and extracellular mechanisms. We previously demonstrated that lysophosphatidic acid (LPA), a lipid growth factor, has opposing regulatory effects on erythrocyte differentiation through activation of LPA receptors 2 and 3; yet the mechanisms underlying this process remain unclear. In this study, LPA2 is observed that highly expressed in common myeloid progenitors (CMP) in murine myeloid cells, whereas the expression of LPA3 displaces in megakaryocyte-erythroid progenitors (MEP) of later stage of myeloid differentiation. Therefore, we hypothesized that the switching expression of LPA2 and LPA3 determine the hematic homeostasis of mammalian megakaryocytic-erythroid lineage. In vitro colony-forming unit assays of murine progenitors reveal that LPA2 agonist GRI reduces the erythroblast differentiation potential of CMP. In contrast, LPA3 agonist OMPT increases the production of erythrocytes from megakaryocyte-erythrocyte progenitor cells (MEP). In addition, treatment with GRI reduces the erythroid, CMP, and MEP populations in mice, indicating that LPA2 predominantly inhibits myeloid differentiation at an early stage. In contrast, activation of LPA3 increases the production of terminally differentiated erythroid cells through activation of erythropoietic transcriptional factor. We also demonstrate that the LPA3 signaling is essential for restoration of phenylhydrazine (PHZ)-induced acute hemolytic anemia in mice and correlates to erythropoiesis impairment of Hutchinson-Gilford progeria Symptom (HGPS) premature aging expressed K562 model. Our results reveal the distinct roles of LPA2 and LPA3 at different stages of hematopoiesis in vivo, providing potentiated therapeutic strategies of anemia treatment.

Glucocorticoid transiently upregulates mitochondrial biogenesis in the osteoblast.

Glucocorticoid (GC)-induced bone loss is the most prevalent form of secondary osteoporosis. Previous studies demonstrated that long-term incubation of dexamethasone (DEX) induced oxidative stress and mitochondrial dysfunctions, consequently leading to apoptosis of differentiated osteoblasts. This DEX-induced cell death might be the main causes of bone loss. We previously described that DEX induced biphasic mitochondrial alternations. As GC affects mitochondrial physiology through several different possible routes, the short-term and long-term effects of GC treatment on mitochondria in the osteoblast have not been carefully characterized. Here, we examined the expression levels of genes that are associated with mitochondrial functions at several different time points after incubation with DEX. Mitochondrial biogenesis-mediated genes nuclear respiratory factor 1 (Nrf1) and Nrf2 were upregulated after 4-h incubation, and then declined after 24-h incubation, suggesting that mitochondrial biogenesis were transiently upregulated by DEX. In contrast, mitochondrial fusion gene optic atrophy 1 (Opa1) and mitofusin 2 (Mfn2) started to be elevated as the biogenesis started to decrease. Finally, the mitochondrial fission increased and apoptosis becomes prominent. Agree with the mitochondrial biphasic alterations hypothesis, the results suggested an early increase of mitochondrial activities and biogenesis upon DEX stimulation to the osteoblasts. The oxidative phosphorylation and inducible nitric oxide synthase levels increased results in oxidative stress accumulation, leading to mitochondrial fusion, and subsequently fission and triggering the apoptosis. Our results indicated that the primary effects of GC on mitochondria are promoting their functions and biogenesis. Mitochondrial breakdown and the activation of the apoptotic pathways appeared to be the secondary effect after long-term treatment.

4-Aminobiphenyl suppresses homologous recombination repair by a reactive oxygen species-dependent p53/miR-513a-5p/p53 loop.

4-Aminobiphenyl (4-ABP), a well-known human carcinogen, can cause oxidative DNA damage and induce miR-513a-5p. However, the interplay between miR-513a-5p and DNA damage remains unclear. In our result of ChIP assay, we speculated that p53 as transcription factor could regulate miR-513a-5p expression. In addition, we found that miR-513a-5p-induced by 4-ABP could suppress p53 expression and HR repair activity. On the other hand, the levels of p53, miR-513a-5p, and γH2AX were attenuated by 5 mM N-acetyl-l-cysteine (NAC) pretreatment, indicating that the reactive oxygen species (ROS)-dependent p53-miR-513a-5p was involved in DSB repair in 4-ABP-treated cells. These findings indicated that the ROS/p53/miR-513a-5p/p53 loop axis plays a relevant role in regulating HR repair which may facilitate our understanding of molecular mechanisms regarding how miR-513a-5p impacts DSB repair in 4-ABP-treated cells.

4-Aminobiphenyl inhibits the DNA homologous recombination repair in human liver cells: The role of miR-630 in downregulating RAD18 and MCM8.

4-Aminobiphenyl (4-ABP), a well-known human carcinogen, has been shown to cause oxidative DNA damage and induce miR-630 expression in HepG2 cells treated with 18.75 µM-300 µM for 24 h. However, the underlying mechanism regarding the epigenetic regulation of miR-630 on DNA damage repair in liver cells is still not understood and needs to be investigated. In present study, our results showed that miR-630 was upregulated, resulting in mediating a decrease of DNA homologous recombination (HR) repair in L-02, HepG2 or Hep3B cells. Results from a luciferase reporting experiment showed that RAD18 and MCM8 were the potential targets of miR-630 during DNA damage induction. The downregulation of RAD18 or MCM8 by miR-630 was accompanied by inhibition of HR repair. Conversely, inhibiting miR-630 enhanced the expression of RAD18 and MCM8, and rescued HR repair. Additionally, we proved that the transcription factor CREB was related to miR-630 biogenesis in liver cells. Moreover, the levels of CREB, miR-630 expression, and double-strand breaks (DSBs) were attenuated by 5 mM N-acetyl-L-cysteine (NAC) pretreatment, indicating that reactive oxygen species (ROS)-dependent CREB-miR-630 was involved in DSB repair. These findings indicated that the ROS/CREB/-miR-630 axis plays a relevant role in the regulation of RAD18 and MCM8 in HR repair, which may facilitate our understanding of molecular mechanisms regarding the role of miR-630 downregulating DNA damage repair in liver cells.

Lysophosphatidic Acid and Hematopoiesis: From Microenvironmental Effects to Intracellular Signaling.

Vertebrate hematopoiesis is a complex physiological process that is tightly regulated by intracellular signaling and extracellular microenvironment. In recent decades, breakthroughs in lineage-tracing technologies and lipidomics have revealed the existence of numerous lipid molecules in hematopoietic microenvironment. Lysophosphatidic acid (LPA), a bioactive phospholipid molecule, is one of the identified lipids that participates in hematopoiesis. LPA exhibits various physiological functions through activation of G-protein-coupled receptors. The functions of these LPARs have been widely studied in stem cells, while the roles of LPARs in hematopoietic stem cells have rarely been examined. Nonetheless, mounting evidence supports the importance of the LPA-LPAR axis in hematopoiesis. In this article, we have reviewed regulation of hematopoiesis in general and focused on the microenvironmental and intracellular effects of the LPA in hematopoiesis. Discoveries in these areas may be beneficial to our understanding of blood-related disorders, especially in the context of prevention and therapy for anemia.

Development of a Surfactant-Containing Process to Improve the Removal Efficiency of Phenol and Control the Molecular Weight of Synthetic Phenolic Polymers Using Horseradish Peroxidase in an Aqueous System.

To reduce phenolic pollutants in the environment, many countries have imposed firm restrictions on industrial wastewater discharge. In addition, the current industrial process of phenolic resin production uses phenol and formaldehyde as the reactants to perform a polycondensation reaction. Due to the toxicity of formaldehyde and phenolic pollutants, the main purpose of this research was to design a green process using horseradish peroxidase (HRP) enzymatic polymerization to remove phenols and to produce formaldehyde-free phenolic polymers. In this study, the optimal reaction conditions, such as reaction temperature, pH, initial phenol concentration and initial ratio of phenol, and H2O2, were examined. Then, the parameters of the enzyme kinetics were determined. To solve the restriction of enzyme inactivation, several nonionic surfactants were selected to improve the phenol removal efficiency, and the optimal operation conditions in a surfactant-containing system were also confirmed. Importantly, the molecular weight of the synthetic phenolic polymers could be controlled by adjusting the ratio of phenol and H2O2. The content of biphenols in the products was almost undetectable. Collectively, a green chemistry process was proposed in this study and would benefit the treatment of phenol-containing wastewater and the production of formaldehyde-free phenolic resin in the future.

Calcium-dependent methylation by PRMT1 promotes erythroid differentiation through the p38α MAPK pathway.

Protein arginine methyltransferase 1 (PRMT1) stimulates erythroid differentiation, but the signaling events upstream are yet to be identified. Ca2+ plays crucial roles during erythroid differentiation. Here, we show that Ca2+ enhances methylation during induced erythroid differentiation and that Ca2+ directly upregulates the catalytic activity of recombinant PRMT1 by increasing Vmax toward the substrate heterogeneous nuclear ribonucleoprotein A2. We demonstrate that PRMT1 is essential and responsible for the effect of Ca2+ on differentiation. Depletion of Ca2+ suppresses PRMT1-mediated activation of p38α and p38α-stimulated differentiation. Furthermore, Ca2+ stimulates methylation of p38α by PRMT1. This study uncovers a novel regulatory mechanism for PRMT1 by Ca2+ and identifies the PRMT1/p38α axis as an intracellular mediator of Ca2+ signaling during erythroid differentiation.

The Antithrombotic Function of Sphingosine-1-Phosphate on Human Adipose-Stem-Cell-Recellularized Tissue Engineered Vascular Graft In Vitro.

Adipose stem cells (ASCs) show potential in the recellularization of tissue engineerined vascular grafts (TEVGs). However, whether sphingosine-1-phosphate (S1P) could further enhance the adhesion, proliferation, and antithrombosis of ASCs on decellularized vascular scaffolds is unknown. This study investigated the effect of S1P on the recellularization of TEVGs with ASCs. Human ASCs were derived from lipoaspirate. Scaffolds were derived from human umbilical arteries (HUAs) with treatment of 0.1% sodium dodecyl sulfate (SDS) for 48 h (decellularized HUAs; DHUAs). The adhesion, proliferation, and antithrombotic functions (kinetic clotting time and platelet adhesion) of ASCs on DHUAs with S1P or without S1P were evaluated. The histology and DNA examination revealed a preserved structure and the elimination of the nuclear component more than 95% in HUAs after decellularizaiton. Human ASCs (hASCs) showed CD29(+), CD73(+), CD90(+), CD105(+), CD31(-), CD34(-), CD44(-), HLA-DR(-), and CD146(-) while S1P-treated ASCs showed marker shifting to CD31(+). In contrast to human umbilical vein endothelial cells (HUVECs), S1P didn't significantly increase proliferation of ASCs on DHUAs. However, the kinetic clotting test revealed prolonged blood clotting in S1P-treated ASC-recellularized DHUAs. S1P also decreased platelet adhesion on ASC-recellularized DHUAs. In addition, S1P treatment increased the syndecan-1 expression of ASCs. TEVG reconstituted with S1P and ASC-recellularized DHUAs showed an antithrombotic effect in vitro. The preliminary results showed that ASCs could adhere to DHUAs and S1P could increase the antithrombotic effect on ASC-recellularized DHUAs. The antithrombotic effect is related to ASCs exhibiting an endothelial-cell-like function and preventing of syndecan-1 shedding. A future animal study is warranted to prove this novel method.