Structures and cytotoxicities of three new sesquiterpenes from cultures of Armillaria sp.

Three new sesquiterpene aryl esters,named 10-dehydroxy-melleoliede B(1),1-O-formyl-10-dehydroxy-melleoliede B(2)and 10-oxo-melleoliede B(3)together with six known ones(4-9),were isolated from the cultures of Armillaria sp.The structures of the new compounds were elucidated based on the extensive spectroscopic methods.Compounds 1,2,and 5-9 exhibited moderate cytotoxicities.

Flavonoids with cytotoxicities from the seeds of Pongamia pinnata(L.)Pierre

Twenty-eight compounds,including flavones(2,4-5,7-11),flavonols(1,3,6,21,22),flavanones(12-18),isoflavones(19,20),chalcones(23,24),phenylpropanoids(25,26),and others(27,28)were isolated from the ethanol extract of the seeds of Pongamia pinnata(L.)Pierre and identified on the basis of physic-chemical constants and spectral analysis(NMR,ECD,[α]^20 D).Among them,compounds 16,18,21,23,25 and 26 were obtained from the genus for the first time.The cytotoxicities of the purified flavonoids against H292 cells were evaluated using MTT assays.As a result,compounds 14 and 15 displayed moderate cytotoxicities.

Synthesis and Cytotoxicities of Royleanone Derivatives

Carnosic acid was used as starting material to synthesize royleanone derivatives featured C11–C14 para quinone.The importance of C-20 group of royleanone derivatives was verified by the cytotoxicity assay of royleanonic acid,miltionone I and deoxyneocrptotanshinone.Following our synthetic route,15 amide derivatives were synthesized and 8 compounds exhibited moderate cytotoxic activities against three human cancer lines in vitro.

Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy

Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.

Recent progress and future directions of the research on nanoplastic-induced neurotoxicity

Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as environmental pollutants that can pose health risks to a wide variety of living organisms,including humans.However,it is not well understood how microplastics and nanoplastics affect cellular functions and induce stress responses.Humans can be exposed to polystyrene-microplastics and polystyrene-nanoplastics through ingestion,inhalation,or skin contact.Most ingested plastics are excreted from the body,but inhaled plastics may accumulate in the lungs and can even reach the brain via the nose-to-brain route.Small-sized polystyrene-nanoplastics can enter cells by endocytosis,accumulate in the cytoplasm,and cause various cellular stresses,such as inflammation with increased pro-inflammatory cytokine production,oxidative stress with generation of reactive oxygen species,and mitochondrial dysfunction.They induce autophagy activation and autophagosome formation,but autophagic flux may be impaired due to lysosomal dysfunction.Unless permanently exposed to polystyrene-nanoplastics,they can be removed from cells by exocytosis and subsequently restore cellular function.However,neurons are very susceptible to this type of stress,thus even acute exposure can lead to neurodegeneration without recovery.This review focuses specifically on recent advances in research on polystyrene-nanoplastic-induced cytotoxicity and neurotoxicity.Furthermore,in this review,based on mechanistic studies of polystyrene-nanoplastics at the cellular level other than neurons,future directions for overcoming the negative effects of polystyrene-nanoplastics on neurons were suggested.

Noscapine shows antimalarial activity against Plasmodium falciparum 3D7,its clinical isolate Pf140/SS,and Plasmodium berghei ANKA

Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.

Enhanced in-vitro degradation resistance and cytocompatibility of a thermomechanically processed novel Mg alloy:Insights into the role of microstructural attributes

The role of microstructural features on in-vitro degradation and surface film development of a thermomechanically processed Mg-4Zn-0.5Ca-0.8Mn alloy has been investigated employing electrochemical studies,scanning electron microscopy and X-ray photoelectron spectroscopy.The specimen forged at 523 K temperature developed a coarse unimodal microstructure consisting of basal oriented grains,whereas the specimens forged at 623 K and 723 K temperatures exhibited bimodal microstructures containing randomly oriented fine grains and basal oriented coarse grains.The bimodal microstructures exerted higher resistance to corrosion compared to the unimodal microstructure in presence of a protective surface film.The optimum size distribution of fine and coarse grains as well as the prevalence of basal oriented grains led to the lowest anodic current density in the specimen forged at 623 K.The morphology of Ca_(2)Mg_(6)Zn_(3)precipitates governed the cathodic kinetics by controlling the anode to cathode surface area ratio.Despite the specimen forged at 723 K comprised comparatively lower fraction of precipitates than at 623 K,the mesh-like precipitate morphology increased the effective cathodic surface area,leading to enhanced localised corrosion in the former specimen.Optimal microstructural features developed at 623 K forging temperature formed a well-protective surface film with lower Mg(OH)_(2)to MgO ratio,exhibiting distinctly high polarization resistance and superior cytocompatibility in terms of cell-proliferation and cell-differentiation.

Anticancer Activity of Rice Callus Suspension Cultures from Aromatic Varieties and Metabolites Regulated in Treated Cancer Cell Lines

Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects.

A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

Cancer frequently develops resistance to the majority of chemotherapy treatments.This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro experimentation.The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 cells.Interestingly,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth.Notably,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate levels.Moreover,this effect was found to be dependent on the dosages of the drugs.In addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression.This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of DOX.The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

Impact of scandium and terbium on the mechanical properties,corrosion behavior,and biocompatibility of biodegradable Mg-Zn-Zr-Mn alloys

Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone repair.Rare earth elements(REEs)have demonstrated their effectiveness in tailoring the corrosion and mechanical behavior of Mg alloys.This study methodically investigated the impacts of scandium(Sc)and terbium(Tb)in tailoring the corrosion resistance,mechanical properties,and biocompatibility of Mg–0.5Zn–0.35Zr–0.15Mn(MZZM)alloys fabricated via casting and hot extrusion.Results indicate that addition of Sc and Tb improved the strength of MZZM alloys via grain size reduction and solid solution strengthening mechanisms.The extruded MZZM–(1–2)Sc–(1–2)Tb(wt.%)alloys exhibit compressive strengths within the range of 336–405 MPa,surpassing the minimum required strength of 200 MPa for bone implants by a significant margin.Potentiodynamic polarization tests revealed low corrosion rates of as–cast MZZM(0.25 mm/y),MZZM–2Tb(0.45 mm/y),MZZM–1Sc–1Tb(0.18 mm/y),and MZZM–1Sc–2Tb(0.64 mm/y),and extruded MZZM(0.17 mm/y),MZZM–1Sc(0.15 mm/y),MZZM-2Sc(0.45 mm/y),MZZM-1Tb(0.17 mm/y),MZZM-2Tb(0.10 mm/y),MZZM–1Sc-1Tb(0.14 mm/y),MZZM-1Sc-2Tb(0.40 mm/y),and MZZM–2Sc–2Tb(0.51 mm/y)alloys,which were found lower compared to corrosion rate of high-purity Mg(~1.0 mm/y)reported in the literature.Furthermore,addition of Sc,or Tb,or Sc and Tb to MZZM alloys did not adversely affect the viability of SaOS2 cells,but enhanced their initial cell attachment,proliferation,and spreading shown via polygonal shapes and filipodia.This study emphasizes the benefits of incorporating Sc and Tb elements in MZZM alloys,as they effectively enhance corrosion resistance,mechanical properties,and biocompatibility simultaneously.

Multi‑omics integration identifies regulatory factors underlying bovine subclinical mastitis

Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry.Multi-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease pathogenesis.Therefore,this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data(mRNA and lncRNA),small RNA sequencing data(miRNA)and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes.Results Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis,provided further insights into subclin-ical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis.The abundant genomic and epigenomic signatures with sig-nificant alterations related to subclinical mastitis were observed,including 30,846,2552,1276 and 57 differential methylation haplotype blocks(dMHBs),differentially expressed genes(DEGs),lncRNAs(DELs)and miRNAs(DEMs),respectively.Next,5 factors presenting the principal variation of differential multi-omics signatures were identified.The important roles of Factor 1(DEG,DEM and DEL)and Factor 2(dMHB and DEM),in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed.Each of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical mastitis.Also,networks of impor-tant functional gene sets with the involvement of multi-omics signatures were demonstrated,which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis.Furthermore,multi-omics integration enabled the association of the epigenomic regulatory factors(dMHBs,DELs and DEMs)of altered genes in important pathways,such as‘Staphylococcus aureus infection pathway’and‘natural killer cell mediated cyto-toxicity pathway’,etc.,which provides further insights into mastitis regulatory mechanisms.Moreover,few multi-omics signatures(14 dMHBs,25 DEGs,18 DELs and 5 DEMs)were identified as candidate discriminant signatures with capac-ity of distinguishing subclinical mastitis cows from healthy cows.Conclusion The integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis,which may ultimately lead to the development of more effective mastitis control and management strategies.

A therapeutic potentiality and toxicity concern of nutrient plant Annona squamosa Linn.

Annona squamosa Linn.fruit is famous for its nutritional value with a long history of medicinal benefits due to the presence of many phytochemicals,including alkaloids,diterpenes,essential oil,phytopeptides,etc.Several studies envisaged that Annona squamosa possesses cytotoxic,diuretic,antiurolithiatic,antitumor,anti-psoriatic,antioxidant,and hepatoprotective properties.This plant is traditionally used for the treatment of wound infection,dysentery,seizure,tumors,fever,vomiting,parasitic infections,hypertension,thyroid,toothache,acne,heart disease,inflammation,diabetes,hair loss,dandruff,hemorrhage,maggot-infected sores,abortifacient,and cough.However,some chemical constituents isolated from the plant have shown specific toxic effects in human and animal models,such as acute oral toxic effects,genotoxic,neurotoxic,and ocular toxic.The plant has diverse pharmacological actions,the seeds of this plant possess a genotoxic effect but on the contrary,the bark of the plant shows genoprotective activity.A large number of ethnobotanical studies reported the seed of this plant is used to induce abortion in humans,but a scientific study carried out in pregnant rats reported aqueous seed extract of the plant did not interfere with reproductive performance.The presented review summarized the traditional uses,pharmacological,and toxicological activities of the isolated compounds from this plant.Additionally,some patents and commercial products related to Annona squamosa are also brought up in this article to explore its application which would attract the scientific community to search out its hidden side.

Reconceptualization of immune checkpoint inhibitor-associated gastritis

In recent years,with the extensive application of immunotherapy in clinical practice,it has achieved encouraging therapeutic effects.While enhancing clinical efficacy,however,it can also cause autoimmune damage,triggering immunerelated adverse events(irAEs).Reports of immunotherapy-induced gastritis have been increasing annually,but due to its atypical clinical symptoms,early diagnosis poses a certain challenge.Furthermore,it can lead to severe complications such as gastric bleeding,elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted.Therefore,gaining a thorough understanding of the pathogenesis,clinical manifestations,diagnostic criteria,and treatment of immune-related gastritis is of utmost importance for early identification,diagnosis,and treatment.Additionally,the treatment of immune-related gastritis should be personalized according to the specific condition of each patient.For patients with grade 2-3 irAEs,restarting immune checkpoint inhibitors(ICIs)therapy may be considered when symptoms subside to grade 0-1.When restarting ICIs therapy,it is often recommended to use different types of ICIs.For grade 4 irAEs,permanent discontinuation of the medication is necessary.

Clinical evaluation of sintilimab in conjunction with bevacizumab for advanced colorectal cancer with microsatellite stable-type after failure of first-line therapy

BACKGROUND At present,immune checkpoint inhibitors(ICIs)remain the 1st-line therapy me-thod for patients suffering from high microsatellite instability/deficient misma-tch repair metastatic colorectal cancer(mCRC).However,ICI treatments demon-strate minimal therapeutic efficacy against microsatellite stable(MSS)/proficient mismatch repair(pMMR)CRC.This is mainly because this type of tumor is a“cold tumor”with almost no lymphocyte infiltration.Anti-angiogenic drugs have been found to improve the immune microenvironment by promoting many immune cells to enter the immune microenvironment,thereby exerting anti-tumor effects.AIM To investigate the effects of ICIs combined with bevacizumab monoclonal anti-body on tumor immune cells in MSS/pMMR advanced CRC patients with first-line treatment failure.METHODS A total of 110 MSS/pMMR patients with advanced CRC after first-line treatment failure in the Affiliated Hospital of Qinghai University were enrolled for a ran-domized controlled trial.In short,patients in the experimental group(n=60)were given sintilimab plus bevacizumab for 4 cycles,and those in the control group(n=50)patients were treated with FOLFIRI combined with bevacizumab for 4 cycles.The expression levels of cluster of differentiation(CD)8(+)T cells,tumor-associated macrophages(TAMs),and cancer-associated fibroblasts(CAFs)were comprehensively evaluated to assess the effects of sintilimab combined with bevacizumab on MSS/pMMR advanced CRC sufferers following failure of 1st-line therapy.RESULTS The positive expression rates of CD8(+)T lymphocytes(30%vs 50%),TAMs(23.30%vs 60%),and CAFs(23.30%vs 50%)before and after treatment in both groups exhibited statistical significance(P<0.05).Additionally,the therapeutic effects of both groups(partial remission:26.67%vs 10%;objective response rate:26.70%vs 10%)were significantly different(P<0.05).Although the experimental group showed a higher progression-free survival,median progression-free survival,and disease control rate than the control group,the difference was not statist-ically significant.Moreover,no significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups was found(P>0.05).CONCLUSION ICIs in combination with bevacizumab can not only improve the patient’s prognosis but also yield safe and controllable adverse drug reactions in patients suffering from MSS/pMMR advanced CRC after failure to a 1st-line therapy.

Advanced cervix cancer patient with chemotherapy-induced grade IV myelosuppression achieved complete remission with cadonilimab:A case report

BACKGROUND The prognosis for patients with advanced metastatic cervix cancer(MCC)is poor,and this disease continues to pose a considerable therapeutic challenge.Despite the administration of first-line regimens consisting of cisplatin,paclitaxel,and bevacizumab,survival rates for patients with metastasis remain poor.The emergence of bispecific antibodies(BsAbs)offers a novel treatment option for patients diagnosed with MCC.CASE SUMMARY In this report,we present a patient with MCC who was treated with cadonilimab monotherapy at a dose of 6 mg/kg every two weeks after chemotherapy was proven to be intolerable.The patient exhibited a sustained complete response for a duration of 6 months,demonstrating an optimistic outlook.CONCLUSION This case illustrates the considerable efficacy of cadonilimab for treating advanced MCC.Therefore,BsAb therapy is a promising strategy for effectively treating patients with advanced MCC and should be considered as an option when patients are intolerant to standard chemotherapy.

Bioremediation of Textile Azo Dyes Amido Black 10B, Reactive Black 5, Reactive Blue 160 by Lentinus squarrosulus AF5 and Assessment of Toxicity of the Degraded Metabolites

Bioremediation is an eco-compatible and economical approach to counter textile dye menace. The isolated Lentinus squarrosulus AF5 was assessed for decolourization of textile azo dyes, and had shown ~93%, 88% and 70% decolorization of Reactive blue 160 (RB160), Reactive black 5 (RB5) and Amido black 10B (AB10B) respectively. Further analysis using UV-vis, HPLC, and FTIR, 1H NMR had shown the degradation of the dyes. Toxicity analysis of the metabolites was performed using seed germination and plant growth on two agriculturally important plants Guar (Cyamopsis tetragonoloba) and wheat (Triticum aestivum) as well as cytotoxicity analysis using the human keratinocyte cell line (HaCaT). The dye mix appeared inhibitory for seed germination (20% - 40%), whereas metabolites were non-inhibitory for germination. Treatment of HaCaT cells with of dye mix and metabolites led into 45% and ~100% of cell viability of HaCaT cells respectively. Therefore, metabolites following degradation of the dye mix were observed to be non-toxic.

Cytotoxic Properties on Cervical and Liver Cancer Cells of Two Plant Recipes from Burkina Faso

Cancer is one of the deadliest diseases in developing countries. In recent years, natural plant-based compounds have been used in the search for drugs to combat numerous diseases, including cancer. In this study, we evaluate the cytotoxic properties of paanfo tiben 1 and paanfo tiben 2, two traditional herbal formulations from Burkina Faso used in the treatment of cancer in Burkina Faso. To this end, the recipes were infused and freeze-dried. The dry extracts obtained were used to determine total phenolics and flavonoids content, assess antioxidant activity using the DPPH, ABTS and FRAP methods, evaluate anti-inflammatory properties by inhibiting 15-LOX, COX 1 and 2, and assess cytotoxic activity on HeLa cervical cancer and HePG2 liver cancer cell lines using the MTT test. The paanfo tiben 1 recipe showed the highest levels of total phenolics and flavonoids, as well as the best antioxidant activities, with IC50 values of 21.020 ± 0.6 µg/ml and 22.94 ± 0.57 µg/ml for DPPH and ABTS, and 165.15 mM EAA/mg dry extract for FRAP. It also exhibited the best cytotoxic activity with IC50 values of 112.02 ± 0.025 µg/ml on HeLa cells and 80.67 ± 6.08 µg/ml on HepG2 cells. On the other hand, paanfo tiben 2 exhibited the best anti-inflammatory activities through inhibition of 15-LOX and COX 1, with inhibition percentages at 100 µg/ml of 32.523% and 24.717 % respectively. These results could justify the traditional use of these two recipes by traditional health practitioners in the treatment of cancer sufferers in Burkina Faso.

Magnetic Field Emulations of Small Inhibitor RNA: Effects on Implanted GL261 Tumors in C57BL/6 Immune Competent Mice

EMulate Therapeutics has developed a system for emulating the effects of solvated molecules via their magnetic field recordings. Recordings of magnetic field emissions of select small inhibitor RNAs (siRNAs;murine targeting CTLA-4 and murine targeting PD-1) were tested on C57Bl/6 mice implanted subcutaneously with the GL261 murine tumor cell line. A signal composed of concatenated recordings of siRNA molecules targeting the murine CTLA-4 and PD-1 receptors (labeled A2) was used in immune competent C57Bl/6 mice. The mice were flank implanted with the murine glioblastoma cell line GL261. Mice were exposed to the signal continuously (24 hours a day) until tumor volumes reached the designated volume limit. Tumors were excised and analyzed via PAGE/Western blot for the expression of CTLA-4, PD-1, Ki67, Caspase 3, CD4 and CD8. Terminal blood draws were used for CBCs. We report the down regulation of the checkpoint inhibitors CTLA-4 in the exposed mice. Significant tumor volume reduction was observed in mice exposed to the siRNA signal compared to control mice;no adverse events were recorded. Cell blood counts (CBC) and protein expression patterns were observed to correlate with the expected function of protein expression inhibition of the targets.

Steroidal constituents from Helleborus thibetanus and their cytotoxicities

Thibetanosides E-H(1-4),four new steroidal constituents including three rare sulfonates(2-4),were isolated from the roots and rhizomes of Helleborus thibetanus,together with nine known steroidal compounds(5-13).Their structures were elucidated by detailed spectroscopic analysis,including 1D and 2D NMR techniques and chemical evidence.In this study,compounds 2-13 were evaluated for their cytotoxic activities against HCT116,A549 and HepG2 tumor cell lines in vitro.Among them,compound 8(thibetanoside C)showed cytotoxicities against A549 cells(IC50 39.6±1.9μmol·L^-1)and HepG2 cells(IC50 41.5±1.1μmol·L^-1),respectively.Compound 9(23S,24S)-24-[(O-β-D-fucopyranosyl)oxy]-3β,23-dihydroxy-spirosta-5,25(27)-diene-1β-yl O-(4-O-acetyl-α-L-rhamnopyranosyl)-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside)showed cytotoxicity against HCT116 cells(IC5033.6±2.1μmol·L^-1).

Microstructures, mechanical properties, corrosion, and biocompatibility of extruded Mg-Zr-Sr-Ho alloys for biodegradable implant applications

In this study,the microstructures,mechanical properties,corrosion behaviors,and biocompatibility of extruded magnesium-zirconiumstrontium-holmium(Mg-Zr-Sr-Ho)alloys were comprehensively investigated.The effect of different concentrations of Ho on the microstructural characteristics,tensile and compressive properties,corrosion resistance,and biocompatibility were investigated.The microstructures of the extruded Mg-1Zr-0.5Sr-xHo(x=0.5,1.5,and 4 wt.%)alloys consisted ofα-Mg matrix,fineα-Zr particles,and intermetallic phase particles of Mg_(17)Sr_(2) and Ho_(2)Mg mainly distributed at the grain boundaries.Extensive{1012}tensile twins were observed in the partially recrystallized samples of Mg-1Zr-0.5Sr-0.5Ho and Mg-1Zr-0.5Sr-1.5Ho.Further addition of Ho to 4 wt.%resulted in a complete recrystallization due to activation of the particle stimulated nucleation around the Mg_(17)Sr_(2) particles.The evolution of a rare earth(RE)texture was observed with the Ho addition,which resulted in the weakened basal and prismatic textures.Furthermore,a drastic increase of 200%in tensile elongation and 89%in compressive strain was observed with Ho addition increased from 0.5 to 4 wt%,respectively.The tension-compression yield asymmetry was significantly decreased from 0.62 for Mg-1Zr-0.5Sr-0.5Ho to 0.98 for Mg-1Zr-0.5Sr-4Ho due to the weakening of textures.Corrosion analysis of the extruded Mg-Zr-Sr-Ho alloys revealed the presence of pitting corrosion.A minimum corrosion rate of 4.98 mm y^(−1) was observed in Mg-1Zr-0.5Sr-0.5Ho alloy.The enhanced corrosion resistance is observed due to the presence of Ho_(2)O_(3) in the surface film which reduced galvanic effect.The formation of a stabilized surface film due to the Ho_(2)O_(3) was confirmed through the electrical impedance spectroscopy and XPS analysis.An in vitro cytotoxicity assessment revealed good biocompatibility and cell adhesion in relation to SaOS2 cells.