Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also related to the course and prognosis of bone and joint infections. The multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) is essential for tissue repair after local injury, which is directly related to the recovery of bone, cartilage, and medullary adipose tissue. Our previous studies and the literature indicate that certain antimicrobial agents can regulate the differentiation potential of bone marrow-derived MSCs. Here, in order to systematically analyze the effects of various antimicrobial drugs on local tissue regeneration, we comprehensively review the studies on the effects of these drugs on MSC differentiation, and classify them according to the three differentiation directions (osteogenesis, chondrogenesis, and adipogenesis). Our review demonstrates the specific effects of different antimicrobial agents on bone marrow-derived MSCs and the range of concentrations at which they work, and provides a basis for drug selection at different sites of infection.

Quantitative examination of the inhibitory activation of molecular targeting agents in hepatocellular carcinoma patient-derived cell invasion via a novel in vivo tumor model

Background: The outcomes for patients with advanced hepatocellular carcinoma(HCC) receiving sorafenib are far from satisfactory because of treatment resistance to sorafenib. However, the exact mechanism of resistance to sorafenib remains unclear and it is valuable to establish a novel mouse model to quantitatively analyze the inhibition rates of sorafenib on the invasive growth of HCC cells in the liver.Methods: HCC tissue microblocks derived from patients were cultured and mixed with hydrogel drops. Then, hydrogel drops containing microblocks of HCC tissue were attached onto the surface of the livers of nude mice to form lesions or nodules of HCC. The mice received molecular targeting agents through oral administration. Livers with tumor nodules were harvested for H&E staining(hematoxylin-eosin staining) analysis and H&E staining images were quantitatively analyzed using image J software. The invasive growth of HCC cells into the liver was calculated using the depth of the lesions compared with the total thickness of the liver.Results: Microblocks containing cells derived from HCC patients can form lesions in the liver of nude mice. Oral administration of molecular targeting agents inhibited the invasive growth of HCC cells in the liver of nude mice.Conclusions: The model established in this study involves the invasive growth of HCC cells in the liver of nude mice, and the model allows for the quantitative analysis of the inhibitory effect of molecular targeting agents on the invasion of HCC cells in vivo.

Effects of Intraocular Lens Implantation without Viscoelastic Agents on Corneal Endothelial Cells

Objective: To determine the protective effects of intraocular lens implantation without viscoelastic agents on corneal endothelial cells. Methods: Patients with age-related cataract were randomly divided into two groups: Group A (24 patients, 30 eyes) underwent phacoemulsification and intraocular lens implantation without viscoelastic agents, and group B (21 patients, 30 eyes) underwent phacoemulsification and intraocular lens implantation with viscoelastic agents. The corneal endothelial cell counts, percentages of hexagonal cells, and central corneal thicknesses were evaluated at 1 week, 1 month, and 6 months after surgery. Results: There was no significant difference in preoperative basic characteristics between the two groups (p > 0.05). The postoperative corneal endothelial cell count and percentage of hexagonal cells in both groups decreased compared with preoperative values at 1 week, 1 month, and 6 months after surgery, and the decrease of group A was significantly lower than that of group B at all time points (p p > 0.05). Conclusions: Compared with regular intraocular lens implantation, intraocular lens implantation without viscoelastic agents is less damaging to corneal endothelial cells, resulting in greater corneal safety.

Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

Programmed cell death, antioxidant response and oxidative stress in wheat f lag leaves induced by chemical hybridization agent SQ-1

Male sterility induced by a chemical hybridization agent （CHA） is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in thistudy. CHA induced programmed cell death （PCD） as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling （TUNEL） and DNA laddering analysis. In the early phase, CHA-SQ-1 trig- gered organelle changes arid PCD in wheat leaves accompanied by excess production of reactive oxygen species （O2- and H202） and down-regulation of the activities of superoxide dismutase （SOD）, catalase （CAT） and guaiacol peroxidase （POD）. Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-l-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.

Correlation study of biological characteristics of non-small cell lung cancer A549 cells after transfecting plasmid by microbubble ultrasound contrast agent

Objective: To explore the role of the abnormal expression of miRNAs in the development process of non-small cell lung cancer and the feasibility of ultrasound microbubble-mediated gene therapy after transfecting antisense miRNA-224 and miRNA-122 a plasmids into nonsmall cell lung cancer A549 cells. Methods: Antisense miRNA-224 and miRNA-122 a plasmids were transfected into non-small cell lung cancer A549 cells on the optimal ultrasound microbubble mediated condition. We set up a control group. The cell proliferation activity, apoptosis, invasion ability were detected by MTT assay, Annexin V-PE, Transwell invasion experiment and colony formation assay, respectively. Results: The expression of mi RNA-224 decreased and the expression of miRNA-122 a rose after the plasmids of target genes were transfected into non-small cell lung cancer A549 cells, and there were significant differences when compared with those of the control group(P<0.05). After the plasmids of target genes were transfected into A549 cells, the growth of antisense miRNA-224 and miRNA-122 a were inhibited, and the differences were significant as compared with the control group(P < 0.05). Besides, the inhibition of miRNA-122 a group was the most significant and there was statistically significant difference as compared with miRNA-224 group(t =-4.694, P = 0.009). After the plasmids of target genes were transfected into A549 cells, the proportion of apoptotic cells increased, the invasive cells were decreased and the clone ability reduced, and also there was a significant difference as compared with those of the control group(P < 0.05). What's more, the apoptotic peak appeared in miRNA-122 a group. Its invasion ability decreased most obviously(40.25 ± 3.97/visual field), the number of clone ability was 104.93 ± 4.87 and the inhibitory effect was the most obviously. There was statistically significant difference as compared with other groups(P < 0.05). Conclusions: A549 cells transfected by ultrasound microbubble-mediated antisense miRNA-224 and mi RNA-122 a plasmids possessed good transfection efficiency. The cell growth, invasion and colony forming abilities of transfected A549 cells were suppressed, which laid a solid foundation for the gene therapy of non-small cell lung cancer.

TELOMERASE: A NOVEL TARGET OF ANTITUMOR AGENTS

Telomerase activity was found to be high in various human cancers, but absent in most normal tissues. Its expression pattern made it a novel target for antitumor agents. Several strategies against telomerase were presented in this review. Targeting the telomerase RNA component by oligonucleotide/ribozyme was considered to be one of the most hopeful approaches. Some progresses were made in this area, such as the use of PANs and 2–5A antisense compounds. The relationships among telomerase activity and cell differentiation, signal transduction, oncogene, tumor suppressor gene as well as cell cycle modulation also provided a series of valuable ideas in designing anti-telomerase drugs for cancer therapy. In conclusion, although there is still a long way in understanding the mechanism and regulation of telomerase, the advance of studies on telomerase has allowed the development of numerous strategies for the treatment of cancer.

Effects of Cryoprotective Agents on the Bovine Articular Chondrocyte Viability

Cryopreservation is the process of choice for long term preservation of cells and tissues. In this study, the effects of cryoprotective agents, dimethyl sulfoxide(DMSO), glycerol and 1,2 propanediol on the bovine articular chondrocyte viability were examined experimentally. The CPA was added at the concentrations of 0 6, 0 9, 1 2 and 1 5 mol/L and at 4 ℃ and 37 ℃ and removed at 37 ℃ in one step. CPA stepwise addition and removal at 0 6 and 1 2 mol/L and at 37 ℃ was also tested as an alternative protocol. Cell volume excursion during DMSO addition and removal was estimated and correlated well with cell survival rates. Solution makeup affects cell survival rate and a stepwise protocol can improve the cell survival rates significantly.

Comparison of intravitreal anti-vascular endothelial growth factor agents and treatment results in Irvine-Gass syndrome

AIM:To compare the efficacy of bevacizumab,ranibizumab,and aflibercept in pseudophakic cystoid macular edema(CME)patients with Irvine-Gass syndrome(IGS).METHODS:This study is designed as retrospective consecutive case series.Those who developed postoperative pseudophakic CME that refractory to topical treatment and were treated with anti-vascular endothelial growth factor(VEGF)agents included in the study.Optical coherence tomography(OCT)examination including central macular thickness(CMT),total macular volume(TMV),retinal nerve fiber layer(RNFL),ganglion cell layer(GCL)and choroidal thickness(ChT)measurements at the baseline,1 st,3 rd and 6 th month controls were performed.RESULTS:Fifty-nine eyes of 59 patients with CME and other healthy eyes of the patients(Control group)were evaluated.There were 22 eyes of 22 patients in the bevacizumab group(group 1),19 eyes of 19 patients in the ranibizumab group(group 2),and 18 eyes of 18 patients in the aflibercept group(group 3).There was no difference in terms of age,gender,axial length,IOP,and spherical equivalent values.The baseline subfoveal and mean ChT were higher in the IGS group.The difference between the baseline and sixth month values of subfoveal and mean ChT were compared in the CME groups,thinning was observed in all three groups.GCL was thinner in the patient group at the 6 th month of treatment.The resolution time of CME was observed faster in group 1.CONCLUSION:All three anti-VEGF agents seem to be effective in CME but bevacizumab appears to be slightly more cost-effective than the other two alternatives.

Multidrug Resistance P-glycoprotein Function of Bone Marrow Hematopoietic Cells and the ReversalAgent Effect

The multidrug resistance P-glycoprotein (P-gp) expression and func-tion in hematopoietic stem/progenitor cells were studied to investigate whether the inhibition of hematopoietic cell P-gp function by multidrug resistance reversal agent increases the cytotoxicity of chemotherapy drugs on the hematopoietic cells.The expression of P-gp on the surface of CD cells from healthy human marrow was examined by flow cytometry. The multidrug resistance reversal agent MS-209 was used to measure the effects of MS-209 on the Rhodamin-123 uptaking o fCD hematopoietic cells. By using methylcellulose semi-solid culture, normal human granulocyte-macrophage clonal formation unit (CFU-GM) was cultured. The changes in CFU-GM inhibitory rate caused by daunorubicin were determined in the presence or absence of MS-2O9. The results showed that the P-gp expression rate of bone marrow CDL cells was 13. 3 %. MS-209 obviously increased the Rhodamin-123 uptake of CD positive cells. The mean inhibitory rate of daunorubicin for CFU-GM was 29. 6 %, but it was increased to 43. 3 % in the presence of MS-209 with the difference being significant (P< 0. 05). It was concluded that hematopoietic cells expressed P-gp protein and possessed active function- MS-209could inhibit the membrane efflux pump and increase the cytotoxicity of chemotherapy drugs to the clonal growth of hematopoeitic stem cells, suggesting the side effects of these drugs on the hematopoietic system should be taken into consideration in the clinical use.

Stitching Perovskite Grains with Perhydropoly(Silazane)Anti-Template-Agent for High-Efficiency and Stable Solar Cells Fabricated in Ambient Air

All inorganic CsPbI_(3)perovskite solar cells(PSCs)have emerged as disruptive photovoltaic technology owing to their admirable photoelectric properties and the non-volatile active layer.However,the phase instability against moisture severely limits the fabrication environment for the high-efficiency devices,breaking through the confinement region to achieve scalable manufacturing has been the primary issue for future commercialization.Here,we develop a curing-anti-solvent strategy for fabricating high-quality and stable black-phase CsPbI_(3)perovskite films in ambient air by introducing an inorganic polymer perhydropolysilazane(PHPS)into methyl acetate to form anti-template agent.The cross-linked PHPS reduces moisture erosions while the hydrolyzate silanol network(–Si(OH)_(4)^(–))controls the perovskite crystal growth by forming Lewis adducts with PbI_(2)during the fabrication.The polycondensation adduct of Si–O–Si/Si–O–Pb strongly binds to CsPbI_(3)grains as a shield layer to hamper phase transition.Using the inorganic CsPbI_(3)perovskite thin-film with PHPS-modified anti-solvent processing as the light absorber,the n–i–p planar solar cell achieved an efficiency of 19.17%under standard illumination test conditions.More importantly,the devices showed excellent moisture stability,retaining about 90%of the initial efficiency after 1000 h under 30%RH.

Synthesis and biological evaluation of N-Alkylamide derivatives as anti-tumor agents

Background:N-Alkylamides(NAAs),derived from Anacyclus pyrethrum(L.)DC,have potential anti-tumor effects.To explore the molecular mechanism and chemo-preventive capacity of NAAs,we synthesized an NAA(H-10)and evaluated whether it could inhibit the proliferation of B16,HepG2,HeLa,and HCT116 cancer cells in 2D culture.Methods:To evaluate the antiproliferative activity of H-10 in 2D and 3D culture of BD,HepG2,HeLa,and HCT116 cells,multicellular tumor spheroids were constructed to more accurately reflect the cell tumor environment.To visualize nuclear changes related to apoptosis,Hoechst 33258 staining and propidium iodide-Annexin V double staining were performed.Results:Compound H-10 strongly inhibited the growth of all tested cell lines.Hoechst 33258 staining and propidium iodide-Annexin V double staining revealed that H-10 did not cause morphological alterations in the nuclei and moderately induced late apoptosis only when treated at 180 mM.The strongest inhibitory effect was observed in HCT116 cells.Flow cytometry analysis indicated that treatment of HCT116 cells with compound H-10 resulted in robust cell growth arrest in G2 phase in 2D and 3D cell culture;in 3D-cultured HCT116 cells,growth arrest occurred in G1 phase.Treatment with compound H-10 also significantly suppressed angiogenesis of chick chorioallantoic membrane in vivo.Conclusion:Treatment with compound H-10 strongly affected clonogenic survival(in the long-term)and migration of HCT116 cells.Therefore,H-10,a compound of NAAs may be useful for treating cancer because of its anti-neoplastic effect and easy synthesis.

Benefits and risks of erythrocyte-stimulating agents

Chronic kidney disease(CKD)is a common and serious clinical problem.Anemia in patients with advanced CKD,frequently called renal anemia,causes disabling fatigue and diminishes patients’quality of life.Frequent and excess transfusions or iron supplementation are potentially hazardous.Although it remains unclear whether the main factor in the development of renal anemia is the failure of erythropoietin(EPO)production in the kidney or a dysfunction in oxygen sensing exogenous EPO administration is considered a rational treatment.The advent of recombinant human erythropoietin(r Hu-EPO)products has dramatically changed the therapeutic strategy for renal anemia.Although rH u-EPO therapy has improved patients’quality of life and decreased the need for blood transfusions,some potential adverse effects have been reported till date.This brief review discusses the treatment of renal anemia with regard to the following:(1)historical background;(2)effectiveness of r Hu-EPO;(3)some topics regarding the treatment of anemia,including EPO resistance,hemoglobin(Hb)cycling,and adequate Hb levels;(4)major adverse effects of rH u-EPO,including hypertension,thrombotic complications,and pure red cell aplasia;and(5)future problems to be resolved.

Topical biological agents targeting cytokines for the treatment of dry eye disease

Because inflammation plays a key role in the pathogenesis of dry eye disease and Sjogren's syndrome, topical anti-inflammatory agents such as corticosteroids and cyclosporine A have been used to treat inflammation of the ocular surface and lacrimal gland. Systemic biological agents that target specific immune molecules or cells such as tumor necrosis factor(TNF)-α, interferone-α, interleukin(IL)-1, IL-6, or B cells have been used in an attempt to treat Sjogren's syndrome. However, the efficacy of systemic biological agents, other than B-cell targeting agents, has not yet been confirmed in Sjogren's syndrome. Several studies have recently evaluated the efficacy of topical administration of biological agents targeting cytokines in the treatment of dry eye disease. Topical blockade of IL-1 by using IL-1 receptor antagonist could ameliorate clinical signs and inflammation of experimental dry eye. Using a mouse model of desiccating stress-induced dry eye, we have demonstrated that topical application of a TNF-α blocking agent, infliximab, could improve tear production and ocular surface irregularity, decrease inflammatory cytokines and Th-1 CD4+ cells on the ocular surface, and increase gobletcell density in the conjunctiva. Although controversy still remains, the use of topical biological agents targeting inflammatory cytokines may be a promising therapy for human dry eye disease.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still controversial.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for Ad-HCC.METHODS From January 2018 to March 2022,217 Ad-HCC patients were retrospectively enrolled.Among them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance bias.Overall survival(OS)was compared using the Kaplan-Meier curve with the log-rank test.The overall objective response rate(ORR)and major complications were also assessed.RESULTS After PSM,82 patients were included both the T-A group and the T-M group.The ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

基于多Agent和动态逻辑制造单元的车间控制系统研究

根据敏捷化生产的要求 ,分析车间控制系统的多 Agent层次结构。提出动态逻辑制造单元的概念 ,用于组织车间制造系统资源 ,实现在动态多变的环境中车间制造系统快速重组、动态重构的能力。研究在动态逻辑制造单元的组织形式下 ,面向订单的生产调度的实现方法 。

基于Agent的制造单元混合式控制系统研究

为了使单元控制系统具有柔性、开放性和可重配置性等特性,将Agent技术融合到单元控制系统体系结构中,提出了基于Agent的制造单元混合式控制体系结构,并对体系结构中各Agent的功能结构进行了设计。在此基础上,构建了控制系统的开放式软件结构,同时讨论了Agent之间的协商和通讯机制的实现方法。

基于多Agent和合同网的敏捷制造单元调度

分析了敏捷制造单元调度问题的特点 ,以构造的基于多Agent技术的控制系统为基础 ,提出了采用分布式人工智能和协同式求解策略来解决敏捷制造单元调度问题 ,采用合同网技术与启发式规则相结合的方法 ,把传统的集中的和自上而下的求解过程转化为分布的和自下而上的求解过程 ,保证能够有效地解决敏捷制造单元的调度问题 .

基于异构Agent系统的虚拟制造单元

虚拟制造单元是虚拟制造系统的一个重要组成部分。本文分析了Agent系统特点 ,提出了一种基于异构A gent系统的虚拟制造单元 ,并建立了审慎式Agent和反应式Agent并存的系统体系结构。根据系统分层和异构的特点 ,定义了Agent的结构模型及其运行模式。采用过程调用模式与消息模式相结合的方式解决了各Agent之间的通信问题。根据所提出的观点并利用相关的开发工具 。