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Aim: We investigated the antimicrobial and anticancer properties of an ethanol crude extract of Red Sea brown alga (Hormophysa cuneiformis) from Egypt. Methods: Extraction was achieved by mixing 100 g of sample powder with absolute ethanol, incubating at 37 °C overnight in a shaking incubator, and then collecting the extract. The extract's antimicrobial activity was tested using a well diffusion assay against the tested pathogens (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Candida albicans) in comparison to commercial antibiotics. Anticancer activity was assessed using MTT assay on MCF-7, HepG-2, and HEP-2 cell lines. The anticancer mechanism of action against the HepG-2 cell line was investigated using cell cycle analysis, Annexin V, and antioxidant enzymes, in addition to transmission electron microscopy. Results: GC-MS phytoconstituent profile of the extract was dominant with fatty acids. A broad antimicrobial effect against all the pathogenic isolates of E. coli, S. aureus, B. subtitles, and C. albicans was demonstrated, especially at the high concentration in comparison to commercial antibiotics. The extract could inhibit the growth of the tested cell lines. We observed the most significant effect on HepG-2 cells, and the concentration of the extract played a role in the level of inhibition (IC50 of 44.6 ± 0.6 µg/ml). The extract had negligible effects on Vero normal cell lines at the lower concentration, with slight toxicity (90.8% viability) at the highest concentration (500 µg/ml). At this same concentration, the extract caused 80-92% inhibition of the cancer cell lines. The extract appears to have demonstrated promising effects on cancer cells. It induces programmed cell death (apoptosis), arrests the cell cycle, and affects the oxidative/antioxidant balance within the cells, potentially leading to the suppression or elimination of cancer cells. These findings are encouraging and may have implications for cancer treatment or further research in this area. More action of extract was seen against bacteria than fungi, with a wide antibacterial impact against all of the tested isolates, notably at the high concentration in comparison to conventional antibiotics. Conclusion: According to the findings, H. cuneiformis may be a valuable source of chemicals that are both antimicrobial and anticancer.

Context: Clausena excavata Burm. f is a plant used in folklore medicine for the treatment of various ailments in South East Asia. The plant parts contain chemical components that are cytotoxic to many cancer cells. Objective: The study investigated the cytotoxic effects of ethyl acetate, methanol and chloroform C. excavata leaf extracts on the non-small-lung cancer, NCI-H460, cell line. Methods: Based on the 3-(4,5-dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT) assay, among extracts, ethyl acetate C. excavata leaf extract (EACE) was the most potent anti-NCI-H460 cells, with IC50 value of 47.1 ± 6.1 μg/ml. The effects of EACE on NCI-H460 cells were also determined by clonogenic, 4', 6-diamidino-2-phenylindole (DAPI), and annexin-V-fluorescein isothiocyanate/propidium iodide-PI flow cytometric assays. Reactive oxygen species (ROS) production and apoptotic gene expressions was determined via flow cytometry and real-time quantitative PCR, respectively. Results: EACE-treated NCI-H460 cells after 48 h underwent apoptosis as evident by loss of cell viability, cell shrinkage, and chromatin condensation. The results also showed EACE mediated increase in ROS production by the NCI-H460 cells. After 48 h treatment, EACE increased the pro-apoptotic BAX and decreased the anti-apoptotic Bcl-2, Survivin and c-Myc gene expressions. Conclusions: EACE is a potential anti-lung cancer by increasing cancer cell ROS production and apoptosis.

Oplopanax elatus (Nakai) Nakai has a long history of use as an ethnomedicine by the people living in eastern Asia. However, its bioactive constituents and cancer chemopreventive mechanisms are largely unknown. The aim of this study was to prepare O. elatus extracts, fractions, and single compounds and to investigate the herb's antiproliferative effects on colon cancer cells and the involved mechanisms of action. Two polyyne compounds were isolated from O. elatus, falcarindiol and oplopandiol. Based on our HPLC analysis, falcarindiol and oplopandiol are major constituents in the dichloromethane (CH2Cl2) fraction. For the HCT-116 cell line, the dichloromethane fraction showed significant effects. Furthermore, the IC50 for falcarindiol and oplopandiol was 1.7 µM and 15.5 µM, respectively. In the mechanistic study, after treatment with 5 µg/ml for 48 h, dichloromethane fraction induced cancer cell apoptosis by 36.5% (p < 0.01% vs. control of 3.9%). Under the same treatment condition, dichloromethane fraction caused cell cycle arrest at the G2/M phase by 32.6% (p < 0.01% vs. control of 23.4%), supported by upregulation of key cell cycle regulator cyclin A to 21.6% (p < 0.01% vs. control of 8.6%). Similar trends were observed by using cell line HT-29. Data from this study filled the gap between phytochemical components and the cancer chemoprevention of O. elatus. The dichloromethane fraction is a bioactive fraction, and falcarindiol is identified as an active constituent. The mechanisms involved in cancer chemoprevention by O. elatus were apoptosis induction and G2/M cell cycle arrest mediated by a key cell cycle regulator cyclin A.

Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.

Background: Acanthopanax senticosus (Rupr. et Maxim.) is commonly used in Traditional Chinese Medicine. Syringin is a major ingredient of phenolic glycoside in Acanthopanax senticosus. Objective: This study was performed to investigate whether Syringin could protect high glucose-induced bone marrow mesenchymal stem cells (BMSCs) injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling. Methods: BMSCs isolated from both the tibia and femur of mice were induced for osteogenesis. The cell senescence was induced using the high glucose medium. The cells were treated with 10 and 100 μmol/l Syringin. Immunohistochemistry staining was performed to determine the β-galactosidase (SA-β-gal) levels in differentially treated BMSCs. MTT assay and flow cytometry analysis were also performed to assess cell viability and cell cycle. The level of ROS in cells with different treatment was measured by using flow cytometry with DCF-DA staining. Calcium deposition and mineralized matrices were detected with alizarin red and ALP staining, respectively. Osteogenesis related genes OCN, ALP, Runx2, and BMP-2 were detected by RT-PCR. Levels of senescence-related proteins including p53 and p21, as well as JAK2, p-JAK2, STAT3, and p-STAT3 were detected by Western blot analysis. Results: Syringin treatment reversed the phenotypes of senescence caused by high glucose in BMSCs, including the arrest of G0/G1 cell cycle, enhanced SA-β-gal activity, and impaired cell growth. Syringin also decreased the elevated ROS production and the levels of p53, p21, and JAK2/STAT3 signaling activation. In addition, Syringin also enhanced the osteogenic potential determined by ARS and ALP staining, as well as increasing OCN, ALP, Runx2, and BMP-2 expressions. Conclusion: Syringin protects high glucose-induced BMSC injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.

Increasing data has confirmed the potential anticancer properties of Dendrobium, a traditional Chinese herb. However, most anticancer compositions from the plant of Dendrobium were usually extracted by high polar solvent, while weak polar compositions with excellent anticancer activity remained largely unexplored. In this study, the differences between ether extract and ethanol extract of Dendrobium nobile Lindl. on chemical components and anticancer activities were investigated, as well as the anticancer mechanisms among different extracts. The results demonstrated that the ether extract exhibited a stronger anticancer effect than ethanol extract, and its anticancer effect was mainly due to weak polar compounds rather than polysaccharides and alkaloids. Quantitative proteomics suggested that the ether extract significantly stimulated the over-expression of immature proteins, the endoplasmic reticulum stress and unfolded protein response were subsequently induced, the intracellular reactive oxygen species level was seriously elevated, and oxidative stress occurred in the meanwhile. Eventually, autophagy and apoptosis were activated to cause cell death. Our findings demonstrate that the ether extract of D. nobile is a potential candidate for anticancer drug development, and that future research on anticancer drugs derived from medicinal plants should also concentrate on weak polar compounds.

2-chloroethyl ethyl sulfide (CEES) is a vesicant agent, commonly referred to half mustard due to its ability to form monofunctional adducts with DNA. In this study, we evaluated the chemoprotective potential of 13 compounds and their mixtures with sodium 2-mercaptoethanesulfonate (MESNA) against CEES-induced geno- and cytotoxicity in human lung cell line A-549. MESNA, L-glutathione (GSH), thiourea, sodium thiosulfate, hexamethylenetetramine, 4-acetamidophenol, asoxime dichloride (HI-6), N-acetyl-L-cysteine (NAC), sodium pyruvate, myo-inositol, 3-aminobenzamide (3-AB), nicotinamide, and Nω-nitro-L-arginine methyl ester hydrochloride and combinations of these compounds with MESNA were applied 30 min before CEES. DNA alkylation was measured using modified comet assay 1 and 24 h after the exposure. Cell viability was determined using MTT assay at 24 and 72 h. The mono-therapeutical approach identified MESNA and GSH to provide significant chemoprotection. NAC and 3-AB supported DNA damage repair, while cell viability remained unaffected. Mixtures of GSH or NAC with MESNA showed protective synergism against DNA damage. Other compounds or their combinations with MESNA failed due to the potentiation of CEES-induced cytotoxicity. The chemoprotection against CEES remains limited; however, the combination of substances can provide protective synergy and may represent a promising strategy in the treatment of accidental exposure to monoalkylating agents.

The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-37 (Interleukin 37), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. To address the function of IL-37 in NSCLC, we first evaluated IL-37 expression in the human NSCLC tissues; then the IL-37 function was assessed in vitro and in vivo in a xenografted lung tumor model. IL-37 was barely expressed in the NSCLC tissue but highly expressed in the adjacent normal tissue. This expression profile was validated by ELISA (Enzyme-linked immunoassay), western blot and immunohistochemical staining. Recombinant IL-37 could suppress cell migration, invasion and proliferation and promote cell apoptosis in NSCLC cell line A549 and SK-MES-1. IL-37 inhibited the IL-6/STAT3 pathway and also the downstream targets Bcl-2, NEDD9 and Cyclin D1. Overexpressing IL-6 or constitutive active STAT3 eliminated the anti-tumor effects of IL-37. Furthermore, IL-37 expression in vivo could inhibit the cancer development. Our results showed that IL-37 plays an inhibitory role in lung cancer development, possibly through IL-6/STAT3 pathway.

Acute rejection (AR) following heart transplantation (HTx) is a common complication, especially in the early post-HTx period. Mitochondrial DNA (mtDNA), released into circulation from stressed mitochondria, mimics ongoing immune activation and facilitates the release of pro-inflammatory substances. Our study aimed to assess cell-free mtDNA levels to identify early indicators of acute rejection progression. The absolute concentration of cf-mtDNA (cp/μl) was measured in 77 adult patients using quantitative polymerase chain reaction. Blood samples (n = 300) were collected before their corresponding biopsy according to the timeline within the first year post-HTx. The median cf-mtDNA levels in samples with confirmed AR (n = 57) was higher compared to samples without diagnosed rejection (n = 210; Padj < 0.01). When acute cellular (ACR; n = 39) and antibody-mediated rejection (AMR; n = 18) were analyzed separately, only AMR demonstrated higher levels compared to samples without diagnosed rejection (Padj = 0.02). The highest cf-mtDNA levels were detected in samples collected during early post-HTx complications compared to samples without rejection and AR samples (for both Padj < 0.0001). Both ACR and AMR were observed throughout the one-year period, with the majority (3rd quartile) occurring during the first 200 days post-HTx. Post-HTx complications, such as graft dysfunction or acute kidney injury, were observed within the first 11 days, with the majority (71.4%) occurring within 5 days post-HTx. The presence of AR, and specifically AMR, is associated with elevated levels of cf-mtDNA. The increase in plasma cf-mtDNA levels strongly reflects the occurrence of early complications following HTx.

Colorectal cancer (CRC) is an important public health problem estimated as the third most commonly diagnosed cancer worldwide. Naphthoquinones are compounds present in different families of plants and interesting for medicinal chemistry due to their activities as potent inhibitors of human cancer growth. In this way, our study aimed to evaluate the cytotoxicity and selectiveness of four 2,3-triazole-1,4-naphthoquinone derivatives (N1-N4) towards the CRC cell line HT-29 and normal human cells. MTT assay showed that N1, N2, N3 and N4 elicited distinct cytotoxic potency, exhibiting EC₅₀ values of 40.6 ± 1.0, 100.1 ± 1.0, 241.9 ± 1.2 and 101.9 ± 1.1, respectively. Later, flow cytometry in HT-29 cells loaded with propidium iodide (5 μM), indicated the ability of N4 (0.5-50 μM) to induce cell membrane damage. Additionally, calcium imaging experiments were conducted in HT-29 cells loaded with 5 μM Fluo-3/AM to assess intracellular Ca²⁺ (iCa²⁺). Our data demonstrated that N4 induces a fast and strong increase of iCa²⁺ in HT-29 cells, mediated by voltage-gated L-type Ca²⁺ channels activation. In conclusion, our study reported on the cytotoxicity and selectiveness of 1,2,3-triazol substituted 1,4-naphthoquinones towards the HT-29 CRC cell line. Furthermore, we have demonstrated the participation of voltage-gated L-type Ca²⁺ channels in the N4 mechanism.

The aqueous extract of Cichorium intybus (CIE) leaves have shown the properties of protecting against pancreatic β-cell damage by streptozotocin (STZ), but the molecular mechanisms of its protection are not completely elucidated yet. Our current study focuses on elucidating the mechanisms of these preventive effects of CIE in MIN6 cells and an in-vivo model of Wistar rats. CIE offers protection against STZ in MIN6 cells by reducing the pro-oxidants and increasing the activity of the antioxidant enzymes. In vitro results also indicated that CIE inhibited cytotoxicity, reduced Reactive oxygen species (ROS), maintained glucose-stimulated insulin secretion and reduced NF-κB p65 translocation into the nucleus. The group administered with a 250 mg/kg dose of CIE in vivo has shown an ability to maintain blood glucose level and also to preserve the number and morphology of pancreatic islets when compared to the diabetic group treated with STZ. Probably, active compounds like quercetin, rutin, and catechin present in CIE, preserve the integrity of pancreatic islets thereby protecting β-cells from the adverse effects of STZ.

Aim: This study aimed to investigate the phytochemical composition of Psychotria montana extract (PME) and evaluate its inhibitory effects on MCF7 breast cancer cells. Methods: The chemical composition of PME was analyzed using UPLC-QToF-MS. The effects of PME on cell proliferation were evaluated using the MTT assay. Flow cytometry was used for cell cycle and apoptosis analysis. The effects of PME on the transcription of cell cycle control genes were assessed using real-time PCR. Results: UPLC-QToF-MS analysis revealed major compounds of PME, including terpenoids and flavonoids, with the potential to inhibit proliferation, migration, and induce apoptosis in MCF7 cancer cells. PME effectively suppressed MCF7 cell proliferation under 2D culture, with a low IC50 value of 34.7 µg/ml. PME also hindered cell migration (p < 0.01) and reduced spheroid number (p < 0.001) and size (p < 0.001) in serum-free 3D culture. Apoptosis analysis via nuclear staining with DAPI and flow cytometry revealed an increase in the number of apoptotic cells after PME treatment (p < 0.001). Additionally, the PME induced cell cycle arrest at the G0/G1 phase (p < 0.05). PME altered the expression of cell cycle control genes (cyclins and CDKs) as well as cancer suppressor genes including p16, p27, and p53 at the transcriptional level (mRNA). The results of molecular docking suggest that the compounds present in PME exhibit a high binding affinity for CDK3, CDK4, CDK6, and CDK8 proteins, which are essential regulators of the cell cycle. Conclusion: Psychotria montana has the potential to inhibit cancer cells by inducing apoptosis and halting the cell cycle of MCF7 breast cancer cells

Phenazine-1-carboxylic acid has extensive pharmacological activity, including antibiotic and immunomodulatory, but the anticancer activity remains unknown. Treatment of prostate cancer cell line (DU145) with phenazine-1-carboxylic acid stimulated inhibition of cell proliferation in concentration- and time-dependent manner. Dual staining confirmed phenazine-1-carboxylic acid stimulated prostate cancer programmed cell death in time-dependent manner. To investigate the exact mechanism, phenazine-1-carboxylic acid-stimulated oxidative stress and mitochondrial-related apoptotic pathway in human prostate cancer cells were examined in this study. Phenazine-1-carboxylic acid increased the generation of reactive oxygen species (ROS) in prostate cancer cell lines, which triggered the pro-apoptotic JNK signaling. Phosphorylated JNK stimulated the depolarization of mitochondrial membrane potential (ΔΨm) and downregulation of anti-apoptotic protein Bcl-2 related with the upregulation of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in corresponding with loss of ΔΨm, stimulate the increased production of cytochrome c and programmed cell death inducing factor (AIF) from mitochondria, and ultimately induced the caspase-dependent and caspase-independent programmed cell death. Altogether, the present study suggests that phenazine-1-carboxylic acid showed an antitumor activity in prostate cancer cells by reactive oxygen species production and mitochondrial-related apoptotic pathway. The results of the present study offered an insight into the prospective of phenazine-1-carboxylic acid for prostate cancer therapy.

The present study explores pharmacological potential and phytochemicals profiling of Picrorhiza kurroa extracts against mammalian cancer cell lines and pathogenic microbes. Bioactive extracts from roots of Picrorhiza kurroa were recovered in the methanol, 50% aqueous dichloromethane (50 : 50 v/v) and n-hexane. Antimicrobial activity of the bioactive extracts was assessed against selected strains of bacteria and pathogenic fungi. Aqueous dichloromethane extract showed highest zone of growth inhibition (39.06 ± 1.0 mm) towards Staphylococcus aureus bacteria while methanolic extract showed the lowest inhibition (6.3 ± 4.1 mm) to Escherichia coli bacteria. The tested extracts such as methanol and aqueous dichloromethane exhibited higher inhibition antifungal activity against Aspergillus flavus compared to Fusarium oxysporum. As far as cytotoxicity (MTT assay) of the tested extracts is concerned, n-hexane and aqueous dichloromethane extracts were found to be very active against all cancer cell lines (breast cancer MCF7, MDA-MB-231, SKBR3 and ovarian cancer SKOV3). A preliminary phytochemicals profiling was performed in extracts using GC-MS. Several fractions of active extract were separated with HPLC and analyzed using High Resolution Atmospheric Pressure Chemical Ionization Mass Spectrometry (HR-APCI-MS). Two purified compounds (Dihydromikanolide and 1,3-Dicyclohexyl-4-(cyclohexylimino)-2-(cyclohexylethylamino)-3,4-dihydro-1,3-diazetium) were further evaluated for their anticancer activity against ovarian cancer cell line. Our findings depict that all the tested extracts showed considerable anticancer potential through cell viability assays. The purified compound 1 - Dihydromikanolide from methanolic extract was found to be active against ovarian cancer cells and can be explored as a promising nutra-pharmaceutical candidate against ovarian cancer. However, further studies exploring the molecular pathways and in vivo testing are required.

Sickle cell anemia (SCA) is a hereditary disorder that is characterized by tendency of hemoglobin molecules within the erythrocytes to polymerize under hypoxia conditions, deform the red cells, and promote vaso-occlusion and endothelial damage. This disease may be associated with the extracellular release of nucleotides, particularly ATP, ADP and adenosine into the circulation. The aim of this study was to investigate the possible changes in adenine nucleotides and nucleoside metabolizing enzymes as well as their levels in serum of SCA patients. NTPDase, 5'-nucleotidase and adenosine deaminase activities were evaluated in serum obtained from blood samples of 15 SCA treated patients and 15 healthy subjects (control group). The results revealed that there were significant (P < 0.001) elevations in NTPDase, 5'-nucleotidase and ADA activities in serum of SCA treated patients when compared to the control group. Furthermore, no significant (P > 0.05) alteration was observed in ATP, ADP and adenosine levels of both SCA treated and control groups. However, inosine level was significantly (P < 0.05) decreased and hypoxanthine level was higher in SCA treated patients (P < 0.001) when compared to the control group. The results suggest the involvement of purinergic signaling enzymes in the maintenance of the levels of extracellular nucleotides and nucleosides, thus preventing some pathophysiological conditions associated with SCA.

Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1β in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.

The current study explored the in vitro anticancer properties of Mesua ferrea stem bark (SB) extract towards human colon carcinoma HCT116 cells. SB was successively extracted with different solvents using soxhlet apparatus. MTT assay was employed to test toxicity against different cancer and normal cell lines. Active extract (n-Hexane) was fractionated by column chromatography (CC) to get the most active fraction (F-3). Series of in vitro assays were employed to characterize cytotoxic nature of F-3. Antioxidant properties of F-3 were assessed using DPPH, ABTS and FRAP assays followed by GC-MS analysis. Intracellular ROS levels were measured by DCFH-DA fluorescent assay. Finally, cell signalling pathways and their downstream proteins targeted by F-3 were studied using 10-cancer pathway and human apoptosis protein profilers and in silico docking studies. n-Hexane extract and its fraction (F-3) showed potent anti-proliferative effect against HCT 116. Programmed cell death (PCD) studies showed that F-3 modulated the expression of multiple proteins in HCT 116. F-3 showed weak antioxidant activity in all the models, while significant increase in ROS was observed in HCT 116. GC-MS analysis revealed that F-3 was majorly comprised of terpenes. Data of pathway profiler and in silico studies revealed that F-3 down-regulated the expression of NF-κB and HIF-1α pathways. Overall these results demonstrate that anticancer effects of M. ferrea stem bark towards human colon carcinoma are mainly due to its terpenes contents.

Protective effects of electromagnetic fields (EMFs) against oxygen and glucose deprivation (OGD)-induced human mesenchymal stem cell (MSC) death were studied. Cell survival, intracellular calcium and ROS/RNS levels were measured after culturing MSCs for 3 h under OGD with or without EMF exposure. The survival rate of cells cultured under OGD condition was significantly reduced compared to control cells, while cells cultured in OGD with 10 Hz/1 mT EMF exposure had higher survival ratio than that in equivalent non-exposed cells. This protective effect of EMF was not observed at different frequency/intensity combinations such as 10 Hz/0.01 mT, 10 Hz/0.1 mT, 50 Hz/1 mT and 100 Hz/1 mT. ROS/RNS levels of cells cultured under OGD conditions significantly increased compared to the control level while 10 Hz/1 mT EMF alleviated this effect. Intracellular calcium levels in OGD group were higher than control while those in OGD plus 10 Hz/1 mT EMF group were significantly lower than OGD group. Addition of Ca²⁺ chelator promoted protective effects of EMF against OGD-induced MSC death. Our results suggest that 10 Hz/1 mT EMF exposure protects MSCs from OGD-induced cell death and the underlying mechanisms of the protection are reduction of intracellular levels of Ca²⁺ and ROS/RNS.

The purpose of the present study was to investigate neutrophil and monocyte cell population data as novel markers of low cobalamin/folate concentrations and influence of renal function on their usefulness. The study included 284 patients older than 60 years or with dyspepsia symptoms with mean corpuscular volume 80-100 fL and C-reactive protein ≤ 50 mg/l. Subjects were divided according to renal function and further classified based on cobalamin and folate levels. Neutrophil and monocyte volume (NeV, MoV), conductivity (NeC, MoC), light scatter (NeS, MoS) and standard deviations (NeV-SD, MoV-SD, NeC-SD, MoC-SD, NeS-SD, MoS-SD), obtained by Coulter LH750^® Hematology Analyzer (Beckman Coulter, USA), were evaluated along with white blood cell count, hemoglobin, hematocrit, red cell distribution width and homocysteine relative to renal function and cobalamin/folate status. Neutrophil conductivity standard deviation (NeC-SD) had the largest magnitude of the difference between patients with low and normal vitamin levels, was the strongest predictor of low cobalamin/folate concentrations and had the largest area under the curve in detection of vitamin deficiency. Patients with different renal function status and the same cobalamin/folate status did not differ in NeC-SD. In this selected group of patients, NeC-SD was marker of low cobalamin and folate levels regardless of the renal function.

A novel and facile in vitro cell sensing system has been developed with one-step electropolymerization of the conducting polypyrrole(PPy) polymer using RGD peptide as the sole dopant on an indium tin oxide (ITO) surface. The resulted RGD peptide-doped polypyrrole (PPy/RGD) composite film had a robust surface, in which PPy provided a biocompatible matrix for cell growth and a conducting interface for electrical detection, while the RGD peptide entrapped in the PPy matrix conferred the desired biomimetic properties. Using the human lung cancer cell A549 as a model, this system can be used to monitor cell behaviors of proliferation and cytotoxicity.

Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1β were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.

There is a limited number of studies about the constituents of Hypericum olympicum subsp. olympicum and its genotoxic and cytotoxic potency. We examined the possible antigenotoxic/genotoxic properties of methanolic extract of H. olympicum subsp. olympicum (HOE) on human lymphocytes by employing sister chromatid exchange, micronucleus and comet assay and analyzed its chemical composition by GCxGC-TOF/MS. The anti-growth activity against MCF-7 and MDA-MB-231 cell lines was assessed by using the ATP viability assay. Cell death mode was investigated with fluorescence staining and ELISA assays. The major components of the flower and trunk were determined as eicosane, heptacosane, 2-propen-1-ol, hexahydrofarnesyl acetone and α-muurolene. HOE caused significant DNA damage at selected doses (250-750 µg/ml) while chromosomal damage was observed at higher concentrations (500 and 750 µg/ml). HOE demonstrated anti-growth activity in a dose-dependent manner between 3.13-100 µg/ml. Pyknotic nuclei were observed at 100 µg/ml concentration of HOE in both cell lines. In conclusion, HOE demonstrated cytotoxic effects in a cell type-dependent manner, however its genotoxic effects were observed at relatively higher doses.

Sunitinib malate is a small molecule that targets multiple receptor tyrosine kinases and blocks their activity. Receptors targeted by sunitinib are implicated in tumor vascularization and are overexpressed by vascular tumors encountered in infants, namely, hemangiomas. Of note is that there is still no definitive treatment for these commonly occurring tumors of infancy. The purpose of this study was to investigate the effects of sunitinib malate on hemangioma using endothelial cells isolated from a murine model of the neoplasm (sEnd.2). The effects of the drug on cell growth were evaluated using the crystal violet assay and flow cytometry, while the scratch assay was employed to measure cell migration. Proteins associated with cell migration and angiogenesis were detected using western blotting. Sunitinib was investigated further to determine its effects on the production of reactive oxygen species, a parameter associated with the promotion of neovascularization in tumors. The results showed that sunitinib significantly reduced the growth of sEnd.2 cells by causing the cells to accumulate in the sub-G1 phase of the cell cycle, and also induced a significant decrease in the migration of these hemangioma cells (P < 0.05). The western blot assay showed a decrease in the expression of adhesion proteins, focal adhesion kinase and paxillin at IC50 doses, although the expression of cadherin did not change significantly (P < 0.05). In addition, transforming growth factor-β1 (TGF-β1) expression was decreased in sunitinib-treated cells at the same dose. The adhesion proteins as well as TGF-β1 regulate cell movement and have been implicated in tumor progression. Thus, sunitinib malate may have potential in the treatment of hemangiomas.

The use of natural products in cosmetics and pharmacy has risen dramatically in recent years, leading to the overexploitation of flora and fauna worldwide and threatening the environmental sustainability. Microbe-derived components could help to solve the problem due to their independently controllable cultural property. To investigate the potential of microfungi for producing potential novel cosmeceuticals, cerevisterol (1), aloesol (2), 3β,5α,9α-trihydroxyergosta-7,22-diene-6-one (3), and ergosterol peroxide (4) were isolated from the halotolerant fungal strains Penicillium brefeldianum CL6 and Talaromyces sp. S3-Rt-N3. They were then tested for biological properties, including anti-microbial, tyrosinase inhibitory, and wound healing activities. The results revealed the wound-healing potentials of two fungal compounds - (1) and (2) - in terms of cell proliferation promotion in NIH-3T3 murine fibroblasts, and the tyrosinase inhibitory potential of fungal compounds (1), (3), and (4) in the substrates L-tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA). Interestingly, compound (1) exhibited antimicrobial activity against acne-causing bacterium Propionibacterium acnes. These results have revealed new prospects for the application of microorganisms-derived compounds, especially in the cosmetics industry.

The radiosensitizing potential of Plumbagin (PLB) against chemo- and radioresistant B16F1 melanoma cells growing in vitro was investigated. Clonogenic assay revealed a sensitization enhancement ratio (SER) of 1.5 for PLB treatment in combination with radiation. PLB pretreatment for 1 h prior to radiation resulted in elevated intracellular ROS levels compared to the group treated with radiation alone. Alkaline comet assay analysis revealed PLB's potential to enhance the radiation induced DNA damage. Cell cycle studies have shown enhanced G₂/M arrest for combination treatment of PLB with radiation. Cell death exerted by PLB combination was mainly through programmed cell death, involving the depletion of mitochondrial membrane potential, increase in the expression of p53, Bax, Cytochrome c, PARP and Caspase 3 cleavage. In conclusion, this study demonstrates the radiosensitizing potential of PLB to inhibit the growth of melanoma cells in vitro, which may be attributed to the oxidative stress and DNA damage leading to enhanced mitochondria-mediated programmed cell death. Also, this study demonstrate the ability of PLB to augment ionizing radiation induced tumor cell kill which further warrant the avenue for the development of a clinically useful radiosensitizer.

Epidemiological data indicate that selenium status is inversely connected with cancer risk. Animal and human studies have demonstrated that most inorganic and organic forms of selenium compounds have an anticancer action. This work investigated the impact of organic selenium on the multiple signalling pathways involved in the inhibition of the viability of prostate cancer cells. Prostate adenocarcinoma cells (PC-3) were incubated with seleno-l-methionine (SeMet) at four concentrations and cell viability and programmed cell death were determined by the WST-1, BrdU assays and Tali image based cytometer. The expression of chosen cell-cycle regulatory genes was determined by real-time RT-PCR analysis and confirmed at the protein level. SeMet treatment of PC-3 cells resulted in an inhibition of cell proliferation in a dose- and time-dependent manner. The inhibition of proliferation correlated with the up-regulation of gene expression and the protein levels of CCNG1, CHEK1, CDKN1C and GADD45A, whereas SeMet down-regulated the expression of CCNA1 and CDK6 genes. Therefore SeMet inhibits the proliferative activity of prostate cancer cells by a direct influence on the expression of genes involved in the regulation of cell cycle progression.

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic β cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

Purpose: The aim of this study was to investigate whether luteoloside, a flavonoid, could protect human dental pulp cells (HDPCs) against inflammation and oxidative stress induced by methylglyoxal (MGO), one of the advanced glycated end products (AGE) substances. Methods: HDPCs were stimulated with MGO and treated with luteoloside. MTT assay was used to determine cell viability. Protein expression was measured via western blotting. Reactive oxygen species (ROS) were measured with a Muse Cell Analyzer. Alkaline phosphatase activity (ALP) and Alizarin red staining were used for mineralization assay. Results: Luteoloside down-regulated the expression of inflammatory molecules such as ICAM-1, VCAM-1, TNF-α, IL-1β, MMP-2, MMP-9, and COX-2 in MGO-induced HDPCs without showing any cytotoxicity. It attenuated ROS formation and enhanced osteogenic differentiation such as ALP activity and Alizarin red staining in MGO-induced HDPCs. Overall, luteoloside showed protective actions against inflammation and oxidative stress in HDPCs induced by MGO through its anti-inflammatory, anti-oxidative, and osteogenic activities by down-regulating p-JNK in the MAPK pathway. Conclusion: These results suggest that luteoloside might be a potential adjunctive therapeutic agent for treating pulpal pathological conditions in patients with diabetes mellitus.

Cancer research is linked to modern life-sciences, encompassing achievements in virology, yeast-biology, molecular-biology, genetics, systems-biology, bioinformatics, and so on. With these fascinating developments, it's easy to overlook that the fundamental theories and treatment strategies were established in the early 20th century and have remained valid ever since. Therefore, tribute must be paid to the founders of the field. The main hypotheses on carcinogenesis, the genetic model and the metabolic model, and the concept of cancer-treatment with cytotoxic, targeted or metabolic drugs were proposed more than 100 years ago by great minds such as T. Boveri, O. Warburg, and P. Ehrlich. Hence nothing about these cancer concepts is really new. Through development of powerful new technologies, we have been able to decipher the mechanisms of malignant transformation, thus significantly advancing the field. Our own studies have been focused on the cross-talk between cell-growth-signaling and lipid-metabolism in ovarian cancer to find crossover-points for co-targeting in order to achieve synergistic treatment effects. Notably, a side-effect of the application of current methods of molecular-cell-biology is a deeper knowledge of the laws of normal cell-biology and cell-life. Thus we anticipate the field will advance rapidly in the near future.

Cell senescence is intensively related to aging and neurodegenerative diseases. This study aimed to explore the effect and targets of Astragaloside IV against amyloid-beta-induced astrocyte senescence. Oligomerized amyloid-beta was prepared to culture with human astrocytes. The effects of Astragaloside IV were assessed based on SA-β-gal staining analysis, senescence markers (p53, p16INK4, and p21WAF1), neurotrophic growth factor levels (qRT-PCR), and cell proliferation (CCK-8 kit). The targets for Astragaloside IV were predicted, and hsp90aa1 protein was verified using molecular docking. After hsp90aa1 overexpression, the effects of Astragaloside IV on amyloid-beta-induced astrocytes were assessed. Treatment of human amyloid-beta-induced astrocytes with Astragaloside IV can decrease the percentage of SA-β-gal positive cells, downregulate the p53, p16INK4, and p21WAF1 levels, and increase the levels of neurotrophic growth factors (IGF-1 and NGF mRNA) and cell proliferation. Based on target prediction, hsp90aa1 was found to be a potential target of Astragaloside IV. Moreover, cellular experiments demonstrated that exogenously enhanced expression of hsp90aa1 overexpression suppressed the protective effect of Astragaloside IV on amyloid-beta-induced human astrocytes. The results presented here demonstrate that Astragaloside IV could confront amyloid-beta-induced astrocyte senescence via hsp90aa1, possibly opening new therapeutic avenues.