N-Acetylglucosamine mitigates lung injury and pulmonary fibrosis induced by bleomycin.

Lung injury and pulmonary fibrosis contribute to morbidity and mortality, and, in particular, are characterized as leading cause on confirmed COVID-19 death. To date, efficient therapeutic approach for such lung diseases is lacking. N-Acetylglucosamine (NAG), an acetylated derivative of glucosamine, has been proposed as a potential protector of lung function in several types of lung diseases. The mechanism by which NAG protects against lung injury, however, remains unclear. Here, we show that NAG treatment improves pulmonary function in bleomycin (BLM)-induced lung injury model measured by flexiVent system. At early phase of lung injury, NAG treatment results in silenced immune response by targeting ARG1+ macrophages activation, and, consequently, blocks KRT8+ transitional stem cell in the alveolar region to stimulate PDGF Rß+ fibroblasts hyperproliferation, thereby attenuating the pulmonary fibrosis. This combinational depression of immune response and extracellular matrix deposition within the lung mitigates lung injury and pulmonary fibrosis induced by BLM. Our findings provide novel insight into the protective role of NAG in lung injury.

Chitosan oligosaccharide attenuates acute kidney injury and renal interstitial fibrosis induced by ischemia-reperfusion.

Acute kidney injury (AKI) and renal interstitial fibrosis are global clinical syndromes associated with high morbidity and mortality. Renal ischemia-reperfusion (I/R) injury, which commonly occurs during surgery, is one of the major causes of AKI. Nevertheless, an efficient therapeutic approach for AKI and the development of renal interstitial fibrosis is still lacking due to its elusive pathogenetic mechanism. Here, we showed that chitosan oligosaccharide (COS), a natural oligomer polysaccharide degraded from chitosan, significantly attenuates I/R-induced AKI and maintains glomerular filtration function by inhibiting oxidative stress, mitochondrial damage, and excessive endoplasmic reticulum stress both in vitro and in vivo. In addition, long-term administration of COS can also attenuate the proliferation of myofibroblasts, mitigate extra cellular matrix deposition, and thus inhibit the transition of AKI to chronic kidney disease through participating in metabolic and redox biological processes. Our findings provide novel insights into the protective role of COS against acute kidney injury.

Changes in quality components and antioxidant activity of peony seed soy sauce during low-salt solid-state fermentation.

BACKGROUND: In this study, the fermentation conditions of peony seed soy sauce (PSSS) koji were optimized by response surface method, and the quality components and antioxidant activity of PSSS were investigated at different low-salt solid-state fermentation stages. RESULTS: Results of response surface method showed that the optimal fermentation conditions were 460.6 g kg-1 water content, 48.6 h culture time, 31.5 °C culture temperature and ratio 2.1:1 (w/w) of peony seed meal:wheat bran, with the highest neutral protease activity (2193.78 U g-1 ) of PSSS koji. PSSS had the highest amino acid nitrogen (7.69 g L-1 ), salt-free soluble solids (185.26 g L-1 ), total free amino acids (49.03 g L-1 ), essential free amino acids (19.58 g L-1 ) and umami free amino acids (16.64 g L-1 ) at 20 days of fermentation. The highest total phenolics were 5.414 g gallic acid equivalent L-1 and total flavonoids 0.617 g rutin equivalent L-1 , as well as the highest DPPH radical scavenging activity (86.19%) and reducing power (0.8802, A700 ) of PSSS fermented at 30 days. Sensory evaluation showed that fermentation of 20 days and 25 days could produce a better taste and aroma of PSSS than 15 days and 30 days. CONCLUSION: PSSS had the highest quality components in the middle of fermentation (20 days) and the highest antioxidant activity in the late fermentation period (30 days). These results demonstrated that peony seed meal could be used to produce high-quality soy sauce with high antioxidant activity. © 2023 Society of Chemical Industry.

Whole-exome sequencing of a patient with primary central nervous system T-cell lymphoma: Clinicopathological features and genomic profiling.

Primary central nervous system T-cell lymphoma (T-PCNSL) is a rare neoplasm, and its underlying genetic features are poorly understood. Herein, we present the case of a 64-year-old man with T-PCNSL who presented with left-side limb weakness. Brain magnetic resonance imaging revealed a right parietal space-occupying lesion. Immunohistochemically, the tumor was positive for CD3, CD4, CD5, CD8, and CD56, and the Ki-67 labeling index was approximately 20%. These pathological features are consistent with those of T-cell lymphoma. Whole exome sequencing was performed, and we found a variant in the ACSS3 gene that could be related to disease pathogenesis. Our findings may help advance our understanding of the molecular pathogenesis of T-PCNSL. Further molecular analysis of such cases could help to improve adjuvant molecular diagnostic methods and targeted therapies for T-PCNSL.

Cinnamaldehyde causes developmental neurotoxicity in zebrafish via the oxidative stress pathway that is rescued by astaxanthin.

Toxicology studies provide a reliable dose range for the use of compounds. Zebrafish show unique advantages in toxicology research. Cinnamaldehyde (Cin) is one of the main active compounds isolated from Cinnamon trees and other species of the genus Cinnamomum. In this study, we investigated the developmental neurotoxicity of cinnamaldehyde in zebrafish and preliminarily explored its underlying mechanism. Cinnamaldehyde causes developmental neurotoxicity in zebrafish, as evidenced by the damage to ventricular structures, eye malformations, shortened body length, trunk curvature, decreased neuronal fluorescence, and pericardial oedema. Moreover, it can induce abnormal behaviour and gene expression in zebrafish. After treatment with the oxidative stress inhibitor astaxanthin, the behaviour and abnormal gene expression were reversed. All of these data demonstrated that the developmental neurotoxicity of cinnamaldehyde might be attributed to oxidative stress. In addition, this study also confirmed that zebrafish is a reliable model for toxicity studies.

Association analysis of risk genes identified by SCHEMA with schizophrenia in the Chinese Han population.

BACKGROUND: Schizophrenia is a chronic brain disorder. Previously, the Schizophrenia Exome Sequencing Meta-analysis consortium identified 10 highest risk genes related to schizophrenia. This study aimed to analyze the relationship between the 10 highest risk genes identified by the SCHEMA and schizophrenia in a Chinese population. METHODS: A total of 225 variants in 10 genes were screened in a Chinese population of 6836 using a customized array. All variants were annotated through the Variant Effect Predictor tool, and the functional impacts of missense variants were assessed based on sorting intolerant from tolerant and PolyPhen-2 scores. The SHEsisPlus tool was used to analyze the association between risk genes and schizophrenia at the locus and gene levels. RESULTS: At the locus level, no missense variants significantly related to schizophrenia were found, but we detected three missense variants that appeared only in cases, including TRIO p. Arg1185Gln, RB1CC1 p. Arg1514Cys, and HERC1 p. Val4517Leu. At the gene level, five genes (TRIO, RB1CC1, HERC1, GRIN2A, and CACAN1G) with more than one variant analyzed were kept for the gene-level association analysis. Only the association between RB1CC1 and schizophrenia reached a significant level (OR = 1.634; 95% CI, 1.062-2.516; P = 0.025). CONCLUSION: In this study, we determined that RB1CC1 might be a risk gene for schizophrenia in the Chinese population. Our results provide new evidence for recognizing the correlation of these risk genes with the Chinese schizophrenia population.

Serum free fatty acid elevation is related to acute kidney injury in primary nephrotic syndrome.

The aim of this research was to examine the clinical characteristics of acute kidney injury (AKI) in primary nephrotic syndrome (NS) and discuss the relationship between serum lipids and AKI. A total of 1028 patients diagnosed with primary NS with renal biopsy results were enrolled in this study. The patients were divided into AKI (n = 81) and non-AKI (n = 947) groups, and their characteristics were compared using a propensity score analysis for the best matching. Serum free fatty acid (FFA) was an independent predictor for AKI in the postmatch samples (p = 0.011). No significant difference in FFA levels was observed among AKI stages or different pathological types in the AKI and non-AKI groups. The AUC (area under the ROC curve) was 0.63 for FFA levels to distinguish AKI. In primary NS, elevated FFA levels tend to be related to a high risk of AKI. FFAs have diagnostic value and may serve as biomarkers for AKI in NS.

Serum Free Fatty Acids and G-Coupled Protein Receptors Are Associated With the Prognosis of Epithelial Ovarian Cancer.

Purpose: Fatty acid metabolism plays key role in cancer development, and free fatty acid receptors (FFARs) are involved in many cancers. However, the correlation between serum free fatty acids (FFAs)/FFARs levels and ovarian cancer (OC) prognosis remains largely unclear. Methods: A retrospective review of 534 primary OC patients and 1049 women with benign ovarian tumors was performed. Serum FFA levels data were extracted from the electronic medical record system. Repeated FFA results of 101 OC patients treated with standard chemotherapy were collected. The effects of FFAs on cells migration were evaluated in OC cell lines by Transwell assay. Gene Expression Profiling Interactive Analysis (GEPIA) was used to compare FFAR mRNA expression levels in cancer and noncancer tissues. Kaplan-Meier (KM) plotter was employed to analyze their prognostic values. SPSS 23.0 and Graphpad prism 7.0 software was used for analysis and graph construction. Results: FFA levels in the serum of epithelial ovarian cancer (EOC) women were higher than in women with benign ovarian tumors independent of pathology, tumor stage,and grade. FFA levels decreased gradually after chemotherapy. FFAs enhanced the migration of OVCAR3 cells. FFAR1 mRNA expression was lower in OC cells than in control cells. FFAR3 was related to a better prognosis, and FFAR4 was related to poor prognosis in TP-53wild-type and mutated type OC, while FFAR1 and FFAR2 were related to a better prognosis in TP53 wild-type OC but FFAR2 was related to a poor prognosis in TP53-mutant OC. Conclusion: The FFA levels are increased in OC and decreased with chemotherapy. High expression of FFARs was related to the prognosis of OC. The prognostic value of different FFARs differs depending on whether it is a TP53 wild or TP53 mutant ovarian cancer.Targeting FFARs may be an attractive treatment strategy for EOC.

Physicochemical, functional and antioxidant properties of mung bean protein enzymatic hydrolysates.

This study aimed to investigate physicochemical, functional and antioxidant properties of mung bean protein (MBP) enzymatic hydrolysates (MBPEHs) by alcalase, neutrase, protamex, flavourzyme and papain. Physicochemical properties were evaluated by SDS-PAGE, particle size distribution, FTIR, ultraviolet visible and fluorescence spectrophotometries. ABTS, hydroxyl scavenging, Fe2+ chelating activity were used to evaluate antioxidant activity. Enzymolysis with five proteases decreased average particle size, α-helix, ß-sheet, surface hydrophobicity of hydrolysates. Alcalase hydrolysate had the highest degree of hydrolysis (23.55%), absolute zeta potential (33.73 mV) and the lowest molecular weight (<10 kDa). Protamex and papain hydrolysates had higher foaming capacities, emulsification activity indexes, emulsion stability indexes (235.00%, 123.07 m2/g, 132.54 min; 200.10%, 105.39 m2/g, 190.67 min) than MBP (135.03%, 20.03 m2/g, 30.88 min). Alcalase hydrolysate demonstrated the lowest IC50 (mg/mL) in ABTS (0.12), hydroxyl (2.98), Fe2+ chelating (0.22). These results provide support for application of MBPEHs as foaming agent, emulsifier and antioxidant in food industry.

Influence of ultrasound treatment on the physicochemical and antioxidant properties of mung bean protein hydrolysate.

This study aimed to investigate influence of ultrasonic treatment on physicochemical and antioxidant properties of mung bean protein hydrolysate (MPH). Physicochemical properties of MPH were evaluated by Tricine-SDS-PAGE, particle size distribution, fourier transform infrared spectroscopy (FTIR) and fluorescence spectroscopy, among others. Radicals scavenging activities of ABTS, hydroxyl, superoxide anion, Fe2+ chelating ability and reducing power characterized antioxidant activities of MPH. MPH contained four bands of 25.6, 12.8, 10.6 and 4.9 kDa, in which 4.9 kDa was the most abundant. Ultrasonic treatment increased the contents of aromatic and hydrophobic amino acids in MPH. Ultrasonic treatment decreased the content of α-helix of MPH and increased ß-sheet and ß-turn compared to MPH. MPH-546 W (ultrasonic treatment 546 W, 20 min) had the lowest average particle size (290.13 nm), zeta potential (-36.37 mV) and surface hydrophobicity (367.95 A.U.). Antioxidant activities of ultrasonicated-MPH increased with the ultrasonic power, achieving the lowest IC50 (mg/mL) of 0.1087 (ABTS), 1.796 (hydroxyl), 1.003 (superoxide anion) and 0.185 (Fe2+ chelating ability) in 546 W power. These results indicated ultrasonic treatment would be a promising method to improve the antioxidant properties of MPH, which would broaden the application scope of MPH as bioactive components in the food industry.

Novel gain-of-function mutation of TRPC6 Q134P contributes to late onset focal segmental glomerulosclerosis in a Chinese pedigree.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS, OMIM®#603 965) is an overriding cause that leads to end-stage renal disease (ESRD). As a member of TRP superfamily, mutations of TRPC6 gene are closely linked to FSGS. By now, 20 missense mutations have been reported, among them, nine gain-of-function (GOF), and five loss-of-function (LOF) mutations have been recognized according to the effect on TRPC6 channel activity. Systematic investigations of functional mutations will provide valuable evidences for understanding the pathophysiology of TRPC6 involved in FSGS. The aim of this study is to investigate the pathogenicity of a novel TRPC6 mutation p.Q134P in FSGS. METHODS: High-throughput sequencing was performed to analyse 436 genes which are associated with hereditary kidney diseases in a Chinese pedigree. Then we constructed TRPC6 expression plasmids of wide type and variant. Immunofluorescence, cell-surface biotinylation assays and electrophysiology were used to analyse the localization, cell surface expression, and calcium transport activity of TRPC6. RESULTS: A novel variant c.401A>C (p.Q134P) in exon 2 of TRPC6 gene was found. There was no significant difference between the expression levels of p.Q134P mutant and WT TRPC6 protein in the whole cell lysate and cell-surface fraction. Q134P mutant-bearing TRPC6 elicited much higher Ca+ current amplitude than WT. CONCLUSION: We identified a novel GOF mutation p.Q134P of TRPC6 which contributed to late-onset FSGS. Our study expands the mutational spectrum of TRPC6 associated with FSGS and furtherly supports the hypothesis of calcium dose-response dependency that a moderate increased calcium influx elicited a mild FSGS phenotype.

Met-enkephalin improves metabolic syndrome in high fat diet challenged mice through promotion of adipose tissue browning.

Obesity and its related metabolic disorders including insulin resistance and fatty liver become major public health concerns in both developed and developing countries. Brown adipose tissue (BAT), a critical organ of energy expenditure due to thermogenesis, has been considered as an attractive target for prevention or treatment of obesity and obesity related diseases. Previous studies indicate Met-enkephalin (MetEnk) has the potential on adipocyte browning, however, whether MetEnk displays the impact on adipocyte browning in vivo to improve obesity associated morbidities is still unclear. In the present study, we showed that MetEnk effectively prevented high fat diet (HFD) induced C57BL/6J mice weight gain, clearly enhanced glucose tolerance and insulin sensitivity, and dramatically reduced hepatic steatosis in HFD fed mice. Mechanically, MetEnk restored protein kinase A (PKA) signaling pathway in HFD challenged mice and promoted subcutaneous white adipose tissue (WAT) browning. Our study suggests that MetEnk can be considered as a potential therapeutic peptide for diet-induced obesity and metabolic disorders.

Biallelic variants in the ciliary gene TMEM67 cause RHYNS syndrome.

A rare syndrome was first described in 1997 in a 17-year-old male patient presenting with Retinitis pigmentosa, HYpopituitarism, Nephronophthisis and Skeletal dysplasia (RHYNS). In the single reported familial case, two brothers were affected, arguing for X-linked or recessive mode of inheritance. Up to now, the underlying genetic basis of RHYNS syndrome remains unknown. Here we applied whole-exome sequencing in the originally described family with RHYNS to identify compound heterozygous variants in the ciliary gene TMEM67. Sanger sequencing confirmed a paternally inherited nonsense c.622A > T, p.(Arg208*) and a maternally inherited missense variant c.1289A > G, p.(Asp430Gly), which perturbs the correct splicing of exon 13. Overall, TMEM67 showed one of the widest clinical continuum observed in ciliopathies ranging from early lethality to adults with liver fibrosis. Our findings extend the spectrum of phenotypes/syndromes resulting from biallelic TMEM67 variants to now eight distinguishable clinical conditions including RHYNS syndrome.

STAT3 Undergoes Acetylation-dependent Mitochondrial Translocation to Regulate Pyruvate Metabolism.

Cytoplasmic STAT3, after activation by growth factors, translocates to different subcellular compartments, including nuclei and mitochondria, where it carries out different biological functions. However, the precise mechanism by which STAT3 undergoes mitochondrial translocation and subsequently regulates the tricarboxylic acid (TCA) cycle-electron transport chain (ETC) remains poorly understood. Here, we clarify this process by visualizing STAT3 acetylation in starved cells after serum reintroduction or insulin stimulation. CBP-acetylated STAT3 undergoes mitochondrial translocation in response to serum introduction or insulin stimulation. In mitochondria, STAT3 associates with the pyruvate dehydrogenase complex E1 (PDC-E1) and subsequently accelerates the conversion of pyruvate to acetyl-CoA, elevates the mitochondrial membrane potential, and promotes ATP synthesis. SIRT5 deacetylates STAT3, thereby inhibiting its function in mitochondrial pyruvate metabolism. In the A549 lung cancer cell line, constitutively acetylated STAT3 localizes to mitochondria, where it maintains the mitochondrial membrane potential and ATP synthesis in an active state.

Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells.

Glioblastoma stem cells (GSCs) are the initiating cells in glioblastoma multiforme (GBM) and contribute to the resistance of GBM to chemotherapy and radiation. In the present study, we investigated the effects of cardamonin (3,4,2,4-tetrahydroxychalcone) on the self-renewal and apoptosis of GSCs, and if its action is associated with signal transducer and activator of transcription 3 (STAT3) pathway. CD133(+) GSCs, a kind of GSCs line, was established from human glioblastoma tissues. Cardamonin inhibited the proliferation and induced apoptosis in CD133+ GSCs. The proapoptotic effects of temozolomide (TMZ) were further enhanced by cardamonin in CD133+ GSCs and U87 cells in vitro. For in vivo study, injection of 5 × 10(5) cells of CD133+ GSCs subcutaneously (s.c.) into nude mice, 100 % of large tumors were developed within 8 weeks in all mice; in contrast, only one out of five mice developed a small tumor when 5 × 10(5) cells of CD133(-) GMBs cells were injected. Cardamonin also inhibited STAT3 activation by luciferase assay and suppressed the expression of the downstream genes of STAT3, such as Bcl-XL, Bcl-2, Mcl-1, survivin, and VEGF. Furthermore, cardamonin locked nuclear translocation and dimerization of STAT3 in CD133(+) GSCs. Docking analysis confirmed that cardamonin molecule was successfully docked into the active sites of STAT3 with a highly favorable binding energy of -10.78 kcal/mol. The study provides evidence that cardamonin is a novel inhibitor of STAT3 and has the potential to be developed as a new anticancer agent targeting GSCs. This study also reveals that targeting STAT3 signal pathway is an important strategy for the treatment of human GBM.

Clove extract inhibits tumor growth and promotes cell cycle arrest and apoptosis.

Cloves (Syzygium aromaticum) have been used as a traditional Chinese medicinal herb for thousands of years. Cloves possess antiseptic, antibacterial, antifungal, and antiviral properties, but their potential anticancer activity remains unknown. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of ethyl acetate extract of cloves (EAEC) and the potential bioactive components responsible for its antitumor activity. The effects of EAEC on cell growth, cell cycle distribution, and apoptosis were investigated using human cancer cell lines. The molecular changes associated with the effects of EAEC were analyzed by Western blot and (qRT)-PCR analysis. The in vivo effect of EAEC and its bioactive component was investigated using the HT-29 tumor xenograft model. We identified oleanolic acid (OA) as one of the components of EAEC responsible for its antitumor activity. Both EAEC and OA display cytotoxicity against several human cancer cell lines. Interestingly, EAEC was superior to OA and the chemotherapeutic agent 5-fluorouracil at suppressing growth of colon tumor xenografts. EAEC promoted G0/G1 cell cycle arrest and induced apoptosis in a dose-dependent manner. Treatment with EAEC and OA selectively increased protein expression of p21(WAF1/Cip1) and γ-H2AX and downregulated expression of cell cycle-regulated proteins. Moreover, many of these changes were at the mRNA level, suggesting transcriptional regulation by EAEC treatment. Our results demonstrate that clove extract may represent a novel therapeutic herb for the treatment of colorectal cancer, and OA appears to be one of the bioactive components.

The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and participates in RU486-induced abortion. Excessive uterine bleeding is the most common side effect of RU486-induced abortion; however, its etiopathogenesis has not been fully understood. Therefore, elucidating the correlation between the Th1/Th2/Th17/Treg paradigm and the volume of uterine bleeding may offer novel therapeutic target for reducing uterine bleeding in RU486-induced abortion. Leonurus sibiricus has been used in clinics to reduce postpartum hemorrhage with low toxicity and high efficiency; however, the effective constituents and therapeutic mechanism have not been described. Stachydrine hydrochloride is the main constituent of L. sibiricus, therefore L. sibiricus is regarded as a candidate for reducing uterine bleeding in RU486-induced abortion mice by regulating the Th1/Th2/Th17/Treg paradigm. AIM OF THE STUDY: The purpose of this study was to determine the Th1/Th2/Th17/Treg paradigm in uterine bleeding of RU486-induced abortion mice and to elucidate the immunopharmacologic effects of stachydrine hydrochloride on inducing the Th1/Th2/Th17/Treg paradigm in reducing the uterine bleeding volume in RU486-induced abortion mice. MATERIALS AND METHODS: To investigate the Th1/Th2/Th17/Treg paradigm in uterine bleeding during RU486-induced abortion mice, pregnant BALB/c mice were treated with high- and low-dose RU486 (1.5mg/kg and 0.9 mg/kg, respectively), and the serum progesterone (P(4)) protein level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells in mice at the maternal-fetal interface were detected by ELISA assay, alkaline hematin photometric assay, and flow cytometry, respectively. To determine the regulatory effect of stachydrine hydrochloride on the Th1/Th2/Th17/Treg paradigm in vitro, splenocytes of non-pregnant mice were separated and treated with P(4,) RU486, and/or stachydrine hydrochloride (10(-5)M, 10(-4)M, and 10(-3)M, respectively). The proportions of Th1/Th2/Th17/Treg cells were analyzed using flow cytometry. To evaluate the effect of stachydrine hydrochloride in reducing uterine bleeding via regulation of the Th1/Th2/Th17/Treg paradigm, pregnant mice were treated with RU486 (1.5mg/kg) and/or stachydrine hydrochloride (2.5mg/kg, 5mg/kg, and 10mg/kg). The serum P(4) level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells at the mice maternal-fetal interface were detected. Moreover, the protein levels of cytokines (IL-12 and IL-6) and the cytokine soluble receptors were analyzed by ELISA assay, and the mRNA expression of transcription factors (T-bet, GATA-3, RORγt, and Foxp3) were detected by RT-PCR assay. RESULT: Th1- and Th17-biased immunity was observed in RU486-induced abortion mice. The volume of uterine bleeding during RU486-induced abortion was negatively related to the proportions of Th1 and Th17 cells, as well as the ratios of Th1:Th2 cells and Th17:Treg cells, and positively related to the proportions of Th2 and Treg cells. Stachydrine hydrochloride promoted the protein expression of IL-12 and IL-6, as well as the mRNA expression of T-bet and RORγt, while inhibiting the mRNA expression of GATA-3 and Foxp3. Therefore, the Th1/Th2/Th17/Treg paradigm in RU486-induced abortion mice shifted to Th1 and Th17 after stachydrine hydrochloride administration. The volume of uterine bleeding during RU486-induced abortion was reduced significantly after stachydrine hydrochloride administration. CONCLUSION: The Th1/Th2/Th17/Treg paradigm is closely related to the volume of uterine bleeding in RU486-induced abortion mice. The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride contributed to the reduction in uterine bleeding in RU486-induced abortion mice.

Induction of apoptosis, G0/G1 phase arrest and microtubule disassembly in K562 leukemia cells by Mere15, a novel polypeptide from Meretrix meretrix Linnaeus.

Mere15 is a novel polypeptide from Meretrix meretrix Linnaeus with cytotoxicity in solid cancer cells. In this study, we investigated its activity on human K562 chronic myelogenous leukemia cells. Mere15 inhibited the growth of K562 cells with IC50 values of 38.2 µg/mL. Mere15 also caused concentration dependent induction of apoptosis, with overproduction of reactive oxygen species and loss of mitochondrial membrane potential. Moreover, Mere15 arrested cell cycle progression at G0/G1 phase of K562 cells in a concentration dependent manner. In addition, Mere15 caused the disassembly of the microtubule cytoskeleton in K562 cells and inhibited the polymerization of tubulin in a cell free system via interaction with tubulin. We concluded that Mere15 was cytotoxic to K562 leukemia cells and the cytotoxicity was related to the apoptosis induction, cell cycle arrest and microtubule disassembly. These results implied that Merer15 was a broad spectrum anticancer polypeptide, not only cytotoxic to various solid cancer cells but also to the chronic myelogenous leukemia cells. Mere15 may have therapeutic potential for the treatment of leukemia.

Poly I:C-induced tumor cell apoptosis mediated by pattern-recognition receptors.

Poly I:C is a synthetic dsRNA that can imitate a viral infection and elicit host immune responses by triggering specific pattern-recognition receptors (PRRs) such as toll-like receptor 3 and retinoic acid inducible gene I(RIG-I)-like receptors, including RIG-I and melanoma differentiation-associated gene 5. Activation of these PRRs by poly I:C triggers a signal transduction cascade that results in the activation of NF-κB and production of type I interferon. Poly I:C has been used as a vaccine adjuvant for cancer immunotherapy for several decades. Evidence from recent studies indicates that poly I:C can directly induce apoptosis in several types of tumor cells, thus providing a new therapeutic approach for cancer treatment. However, the molecular mechanism underlying the induction of apoptosis by poly I:C is still unclear. In this review, we summarize the current knowledge of poly I:C-induced tumor cell apoptosis, focusing on the key molecules and pathways involved in this process.

miR-125b regulates the proliferation of glioblastoma stem cells by targeting E2F2.

microRNAs (miRNAs) play important role in regulating cancer stem cell self-renewal and differentiation, but the expression prolife of miRNAs in glioma stem cells (GSCs) has not been addressed. Here, we found that CD133 positive GSCs possess a unique miRNAs profile compared to CD133 negative glioblastoma cells. miR-125b, as one of neuronal miRNAs, is the most significantly down-regulated miRNAs and overexpression of miR-125b inhibits the proliferation of CD133 positive GSCs and reduces the expression of "stem" marker. Furthermore, two binding sites for miR-125b are identified in the 3'UTR of E2F2 and overexpression of miR-125b in CD133 positive GSCs represses the endogenous level of E2F2 protein. This study demonstrated that miR-125b plays important roles in regulating the proliferation of GSCs by directly targeting E2F2.