Acquired factor XIII deficiency presenting with multiple intracranial hemorrhages and right hip hematoma:A case report

BACKGROUND Factor XIII(FXIII)deficiency is a rare yet profound coagulopathy.FXIII plays a pivotal role in hemostasis,and deficiencies in this factor can precipitate unchecked or spontaneous hemorrhaging.Immunological assays for detecting FXIII inhibitors are indispensable for diagnosing acquired FXIII deficiency;however,the availability of suitable testing facilities is limited,resulting in prolonged turnaround times for these assays.CASE SUMMARY In this case study,a 53-year-old male devoid of significant medical history presented with recurrent intracranial hemorrhages and a hematoma in the right hip.Subsequent genetic analysis revealed a homozygous mutation in the ACE gene,confirming the diagnosis of acquired FXIII deficiency.CONCLUSION This case underscores the significance of considering acquired deficiencies in clotting factors when evaluating patients with unexplained bleeding episodes.

Efficacy of multigrain supplementation in type 2 diabetes mellitus:A pilot study protocol for a randomized intervention trial

BACKGROUND Uncontrolled type 2 diabetes mellitus(T2DM)may lead to microvascular complications(nephropathy,retinopathy,and neuropathy)and cardiovascular diseases.The beta-glucan content in grains has the potential to improve insulin sensitivity,lowering postprandial glucose response and reducing inflammation degrees.A proper combination of grains not only satisfies human body’s need,but also provides essential and reasonable nutritional contents.However,no trial has been conducted to evaluate the roles of multigrain in T2DM.AIM To determine the efficacy of multigrain supplementation among T2DM patients.METHODS From October 2020 to June 2021,a total of 50 adults living with T2DM,who were receiving standard diabetes care at Day Care Clinic,were randomized into either a supplementation group or a control group.The supplementation group received twice daily 30 g multigrain supplement(equivalent to 3.4 g beta-glucan)with standard medication for 12 wk,while the control group was prescribed with standard medication.Parameters such as glycemic control(HbA1c,FPG,and HOMO-IR),cardiometabolic profile(lipid profile,renal function test,and liver function test),oxidative stress status,nutritional status,and quality of life(QoL)were assessed at two time points:Baseline and the end of the treatment period(week 12).RESULTS The primary outcomes were the mean difference of glycated haemoglobin(%),fasting plasma glucose,and serum insulin as intervention effects.Secondary outcomes included the measurement of cardiometabolic profile,antioxidative and oxidative stress status,nutritional status indices,and QoL.Tertiary outcomes involved the determination of safety and tolerability,and supplementation compliance.CONCLUSION The present clinical trial will reveal the effectiveness of multigrain supplementation among T2DM patients for the improvement of diabetes management.

Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy

Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.

Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially presents as benign fat accumulation,it may progress to steatosis,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.Mesenchymal stem cells(MSCs)are recognized for their intrinsic self-renewal,superior biocompatibility,and minimal immunogenicity,positioning them as a therapeutic innovation for liver diseases.Therefore,this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics,and support the development of MSC-based therapy in the treatment of NAFLD.

Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model

BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.

Review on Zinc Oxide Nanoparticles: Antibacterial Activity and Toxicity Mechanism

Antibacterial activity of zinc oxide nanoparticles(Zn O-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. Zn O-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. Zn O is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered Zn O-NPs antibacterial activity including testing methods, impact of UV illumination, Zn O particle properties(size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory concentration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species(ROS) including hydrogen peroxide(H2O2), OH-(hydroxyl radicals), and O2-2(peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to Zn O-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions.These have led to mitochondria weakness, intracellular outflow, and release in gene expression of oxidative stress which caused eventual cell growth inhibition and cell death. In some cases, enhanced antibacterial activity can be attributed to surface defects on Zn O abrasive surface texture. One functional application of the Zn O antibacterial bioactivity was discussed in food packaging industry where Zn O-NPs are used as an antibacterial agent toward foodborne diseases. Proper incorporation of Zn O-NPs into packaging materials can cause interaction with foodborne pathogens, thereby releasing NPs onto food surface where they come in contact with bad bacteria and cause the bacterial death and/or inhibition.

Dual-specificity phosphatase 6(DUSP6): a review of its molecular characteristics and clinical relevance in cancer

Mitogen-activated protein kinases(MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6(DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells. This phosphatase functions in a dual manner, pro-oncogenic or tumor-suppressive, depending on the type of cancer. To date, the tumor-suppressive role of DUSP6 has been demonstrated in pancreatic cancer, non-small cell lung cancer, esophageal squamous cell and nasopharyngeal carcinoma, and ovarian cancer. Its pro-oncogenic role has been observed in human glioblastoma, thyroid carcinoma, breast cancer, and acute myeloid carcinoma. Both roles of DUSP6 have been documented in malignant melanoma depending on the histological subtype of the cancer. Loss-or gain-of-function effects of DUSP6 in these cancers highlights the significance of this phosphatase in carcinogenesis. Development of methods that use the DUSP6 gene as a therapeutic target for cancer treatment or as a prognostic factor for diagnosis and evaluation of cancer treatment outcome has great potential. This review focuses on molecular characteristics of the DUSP6 gene and its role in cancers in the purview of development, progression, and cancer treatment outcome.

Antihyperlipidemic activity of the medicinal plants among Kadazan and Dusun communities in Sabah,Malaysia:a review

Sabah is one of the 13 states within the Federation of Malaysia and is located in the northernmost part of Borneo.It is the second largest state in Malaysia with a landmass of approximately 7.4million hectares.The total forested area is 4.7 million hectares.Sabah,being part of Borneo,is rich in plant biodiversity.There is also an abundance of medicinal plants and other plants for everyday use.There is a great awarness regarding association between low density lipoprotein reduction and decreased cardiovascular disease mortality.The antihyperlipidaemic activity of herbs plays an important role in the reduction of cardiovascular diseases,which is the top disease that causes mortality all over the world.Lipid-lowering activity of medicinal plant for phytomedicine research and drug development for such a disease are now focused all over the world.A plant-based diet rich in fruit,vegetables,and legumes and low in saturated fat is an effective prescription for anyone with more severe atherosclerosis.Howerver,there are few herbs available that provide some protection for persons with the above disease.The antihyperlipidaemia property in plant plays a vital role to reduce atherosclerosis.Thus,there is an increasing search for the lipid lowering agents from natural origin.In this review an attempt has been made to give an overview of the antihyperlipidemic activity in traditional medicinal plants found widely in Kadazan and Dusun communities in Sabah,Malaysia.The antihyperlipidemic activity of the traditional medicinal plants in these communities is more helpful for the development of new drugs used in the protection against dyslipidemia or atherosclerosis.

Antidiabetic and antioxidant activities of Nypa fruticans Wurmb. vinegar sample from Malaysia

Objective: To study the antidiabetic and antioxidant activities of nipa palm vinegar(NPV) used in traditional Malay medicine for treating diabetes. Methods: NPV was extracted using liquid-liquid extraction method and the obtained samples were subjected to antidiabetic studies using normal and streptozotocin-induced diabetic rat models whereas antidoxidant activities were investigated via in vitro antioxidant tests namely 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid free radicals scavenging activities and the reducing power assay. Results: Single administration of NPV and its extracts were not effective in both normal and diabetic rats. In intraperitoneal glucose tolerance test, NPV and its aqueous extract showed significant blood glucose lowering effect. In the sub-acute study, compared with the diabetic control, aqueous extract of NPV showed the most notable blood glucose lowering effect(56.6%) and a significant improvement in serum insulin levels(79.8%, P<0.05). To assess NPV's antioxidant activity, three in vitro antioxidant tests were employed: 2,2-diphenyl-1-picryhydrazyl and 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid free radical-scavenging assays, and the reducing power assay. Ethyl acetate extract had the greatest antioxidant potential and content of phenolic and flavonoid compounds. A linear positive correlation between the antioxidant parameters was observed. Chemical profiling analysis of aqueous extract of NPV revealed the presence of acetic acid(35.25%), the main active constituent which significantly contributed to the observed antidiabetic activity. Conclusions: Aqueous extract of NPV possesses antihyperglycaemic activities comparable to the metformin, while the ethyl acetate extract precipitated significant antioxidant effects attributable to its high phenolic content. These findings suggest that antioxidant compounds of NPV do not contribute much towards the overall observed antidiabetic effect.

Aristolochia gehrtii inhibits liver toxicity and apoptosis in Schistosoma malayensis infection

Objective:To evaluate a protective effect of Aristolochia gehrtii(A.gehrtii)leaves to inhibit liver toxicity and apoptosis in Schistosoma malayensis(S.malayensis)infection.Methods:Forty male albino mice were divided into four equal groups:group 1 control including noninfected healthy mice and groups 2,3&4 subcutaneously infected with S.malayensvs cercariae where groups 3&4 pretreated with A.gehrtii leaves(200 mg/kg,bwt)&cinnamoylamide(250mg/kg,bwt),respectively.Results:5.malayensis caused a significant increase in serum AST,ALT,ALP,MDA,NO,bilirubin,urea,creatinine,total cholesterol,LDL,triglycerides,and HDL levels.The pretreatment of A,gehrtii leaves and cinnamoylamide significantly inhibited that increase.On the other hand,S.malayensis induced a significant decrease in serum total protein,albumin,globulin,albumin/globulin ratio,blood SOD and GPx,while A.gehrtii leaves and cinnamoylamide pretreatment increased the above parameters.Treatment with A.gehrtii leaves and cinnamoylamide to S.malayensis infected mice increased p53 expression but decreased bcl-2expression.These results were supported by hislopalholqgical investigations.Conclusions:A.gehrtii inhibits liver toxicity and apoptosis in S.malayensvs infection and this effect is associated with the major cinnamoylamide ingredient of A.gehrtii leaves.

Nasal airflow of patient with septal deviation and allergy rhinitis

A numerical simulation of a patient’s nasal airflow was developed via computational fluid dynamics.Accordingly,computerized tomography scans of a patient with septal deviation and allergic rhinitis were obtained.The three-dimensional(3D)nasal model was designed using InVesalius 3.0,which was then imported to(computer aided 3D interactive application)CATIA V5 for modification,and finally to analysis system(ANSYS)flow oriented logistics upgrade for enterprise networks(FLUENT)to obtain the numerical solution.The velocity contours of the cross-sectional area were analyzed on four main surfaces:the vestibule,nasal valve,middle turbinate,and nasopharynx.The pressure and velocity characteristics were assessed at both laminar and turbulent mass flow rates for both the standardized and the patient’s model nasal cavity.The developed model of the patient is approximately half the size of the standardized model;hence,its velocity was approximately two times more than that of the standardized model.

Review on pharmacological and toxicologyical effects of oleum azadirachti oil

Oleum azadirachti consists of the oil obtained from dried seeds of Azadirachta indica A.Juss.(family:Meliaceae).Local names of Azadirachta indica A.Juss.are Abodua,aforo-oyinbo,anwe egyane,arista,azad dirakht,azadarakht,azedarach and bead tree.Indigenous to India,and widely distributed in South and South-East Asia and cultivated in Africa,the South Pacific Islands,South and Central America and Australia,and in southern Florida and California,United States of America,it is a straight-boled deciduous tree,which is 6-25 m high.Bark is dark-brown,externally fissured with a buff inner surface and fibrous fracture,Leaves alternately arranged,pinnately compound and up to 40 cm long,and composed of 8-18 short-petiolate narrow-ovate,pointed and curved toothed leaflets,3-10 cm long and 1-4 cm wide arranged in alternate pairs.The major constituents are oxidized tetranortriterpenes including azadirachtin(azadirachtin A),azadiriadione,epoxyazadiradione,azadirone,nimbidin,nimbin,deacelylnimbin,salannin,gedunin,mahmoodin,17-hydroxydiradione and related derivatives.It is of various medicinal uses,such as a contraceptive for intravaginal use,a mosquito repellent,and treatment of vaginal infections,treatment of gastric ulcers,cardiovascular disease,malaria,rheumatism and skin disorders,external applications for treatment of septic wounds,ulcers and boils,treatment of allergic skin reactions,asthma,bruises,colic,conjunctivitis,dysmenorrhoea,fever,gout,headache,itching due to varicella,kidney stones,leukorrhoea,psoriasis,scabies,sprains and muscular pain,and wounds.It is also used as an emmenagogue.tonic,stomatic and vermicide.In conclusion,the plant oil had antifertility,antihyperglycaemic,anti-inflammatory,antimicrobial,antiviral,antiulcer,estrogenic,immune,contraceptive,autibacterial,insect repellent,and skin treatment effects.

裘氏妇科治疗先兆流产的共性规律及常用药对分子机制的研究

目的基于数据挖掘、网络药理学和分子对接分析浙江省裘氏妇科流派治疗先兆流产的中医思辨特征、共性规律,并探讨常用药对的可能作用机制。方法收集省内具有一定影响力的4位裘氏妇科传承人治疗先兆流产的病例,利用SPSS 22.0和Apriori关联规则算法筛选治疗先兆流产的高频药物及药对。应用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选药用药对的活性成分、潜在靶点,并与先兆流产相关靶点作比对,构建“核心靶点-活性成分-药物”网络。运用STRING数据库得到蛋白-蛋白相互作用(protein-protein interaction,PPI)网络。通过Metascape进行基因本体(gene ontology,GO)与京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。使用分子对接和分子动力学对药物关键成分、核心靶点进行验证。结果先兆流产临床常见证型包括肾虚证、血热证、气血虚弱证、血瘀证,针对不同证型,4位医家辨证论治,异中存同,其中菟丝子-白芍是最常用药对。通过TCMSP数据库共筛选出该药对的22种活性成分及125个治疗先兆流产的靶点。GO功能富集分析主要集中于对含氮化合物的反应、脂多糖分子的免疫反应、激酶调节活性等过程。KEGG分析显示主要富集于参与癌症通路和P53信号通路等相关信号通路。分子对接结果显示菟丝子-白芍药对的活性成分槲皮素(quercetin)和山柰酚(kaempferol)能较好地与AKT1、TNF、IL6、TP53、VEGFA、IL1B、JUN、CASP3、EGF和MMP9等靶基因结合,具有潜在较高的生物活性。通过50 ns的分子动力学模拟发现菟丝子-白芍对形成了稳定的分子间作用。结论裘氏妇科治疗先兆流产组方用药多从脾、肾、肝论治,且善用药对,其常用药对“菟丝子-白芍”治疗先兆流产的潜在靶点和作用机制主要参与调控生殖激素水平、炎症反应、免疫平衡、血管生成等生物学过程,为中医药治疗先兆流产提供理论依据,以及进一步发掘其潜在作用机制提供方向。

mRNA transcriptome profiling of human hepatocellular carcinoma cells HepG2 treated with Catharanthus roseus-silver nanoparticles

BACKGROUND The demand for the development of cancer nanomedicine has increased due to its great therapeutic value that can overcome the limitations of conventional cancer therapy.However,the presence of various bioactive compounds in crude plant extracts used for the synthesis of silver nanoparticles(AgNPs)makes its precise mechanisms of action unclear.AIM To assessed the mRNA transcriptome profiling of human HepG2 cells exposed to Catharanthus roseus G.Don(C.roseus)-AgNPs.METHODS The proliferative activity of hepatocellular carcinoma(HepG2)and normal human liver(THLE3)cells treated with C.roseusAgNPs were measured using MTT assay.The RNA samples were extracted and sequenced using BGIseq500 platform.This is followed by data filtering,mapping,gene expression analysis,differentially expression genes analysis,Gene Ontology analysis,and pathway analysis.RESULTS The mean IC 50 values of C.roseusAgNPs on HepG2 was 4.38±1.59μg/mL while on THLE3 cells was 800±1.55μg/mL.Transcriptome profiling revealed an alteration of 296 genes.C.roseusAgNPs induced the expression of stress-associated genes such as MT,HSP and HMOX-1.Cellular signalling pathways were potentially activated through MAPK,TNF and TGF pathways that are responsible for apoptosis and cell cycle arrest.The alteration of ARF6,EHD2,FGFR3,RhoA,EEA1,VPS28,VPS25,and TSG101 indicated the uptake of C.roseus-AgNPs via both clathrin-dependent and clathrinindependent endocytosis.CONCLUSION This study provides new insights into gene expression study of biosynthesised AgNPs on cancer cells.The cytotoxicity effect is mediated by the aberrant gene alteration,and more interestingly the unique selective antiproliferative properties indicate the C.roseusAgNPs as an ideal anticancer candidate.

Anticancer effect of Psidium guajava(Guava) leaf extracts against colorectal cancer through inhibition of angiogenesis

Objective:To evaluate the anti-angiogenic and anticancer activities of Psidium guajava leaf extracts against angiogenesis-dependent colorectal cancer.Methods:Three extracts were produced using distilled water,ethanol,and n-hexane as solvents.The extracts were physically characterised through gas chromatography–mass spectrometry,ultraviolet–visible spectroscopy,and Fourier transform infrared spectroscopy.Their antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl,total phenolic content,and total flavonoid content assays.To assess their anti-angiogenic activity,cell viability and rat aortic ring assays were conducted,while cell migration,tube formation,colony formation,and VEGF ELISA assays were conducted to elucidate their effects on different aspects of angiogenesis.Molecular docking was used to assess the antiangiogenic potential of some possible compounds in the extracts.Tumour spheroid assay was used to assess the extracts’potential as a treatment for colorectal cancer.Results:The ethanol extract showed the best antioxidant activity.The distilled water and ethanol extracts exhibited more inhibitory activity against EA.hy926 cell viability and aortic ring microvessel growth.In addition,the ethanol extract performed significantly better than the distilled water extract against cell migration and colony formation,and VEGF expression of the cells was suppressed by the ethanol extract.Both the distilled water and ethanol extracts showed significant inhibitory effect on EA.hy926 tube formation and tumour spheroids consisting of EA.hy926 and HCT116 cells.The ethanol extract containedβ-caryophyllene andβ-elemene by phytochemical analysis and subsequent docking studies,which may contribute to its anti-angiogenic activity.Conclusions:The ethanol extract of Psidium guajava has potential in the treatment of colorectal cancer through the inhibition of angiogenesis.

Bee pollen extract of Malaysian stingless bee enhances the effect of cisplatin on breast cancer cell lines

Objective: To evaluate the antioxidant and antiproliferative effect of methanolic bee pollen extract(BPE) of Malaysian stingless bee [Lepidotrigona terminata(L. terminata)]and its synergistic effect with cisplatin(a chemotherapeutic drug) on MCF-7 cancer cell line.Methods: The antioxidant activity of BPE from L. terminata was measured by using1,1-diphenyl-2-picrylhydrazyl radical(DPPH) assay. Antiproliferative activity at different concentrations of BPE and cisplatin was determined through using MTT assay on MCF-7 and L929 cell lines. An interaction effect(synergistic, additive and antagonistic) between BPE and cisplatin was determined by Compu Syn software based on MTT assay data.Results: The EC50(50% decrement of DPPH inhibition) of BPE was 0.5 mg/m L.L. terminata BPE exhibited antiproliferative activity on both cancer and normal cell lines.The IC50(concentration of drug that was required for 50% of cell inhibition in vitro) of BPE on MCF-7 was 15 mg/m L whereas in normal cell line L929 was 26 mg/m L. The IC50 for cisplatin on MCF-7 was 20 mmol/L. The combination effect of BPE and cisplatin on MCF-7 cells showed that BPE at 15 mg/m L was able to potentiate the inhibitory effect of cisplatin at all different concentrations(2.5–20.0 mg/m L). The average of cancer cells inhibition which was potentiated by BPE was around 50%. A combination index values of less than 1 reported in the Compu Syn software further proved the synergistic effect between BPE and cisplatin, suggesting that BPE was working synergistically with cisplatin.Conclusions: Our study therefore suggested that BPE of Malaysian stingless bee,L. terminata is a potential chemopreventive agent and can be used as a supplementary treatment for chemotherapy drugs. BPE might be able to be used to potentiate the effect of chemotherapy drugs with the possibility to reduce the required dose of the drugs. The molecular mechanisms of how the BPE exerts antiproliferative activity will be a much interesting area to look for in future studies.

Subacute oral toxicity study of ethanolic leaves extracts of Strobilanthes crispus in rats

Objective:To examine the oral toxicity of repeated dosing of Strobilanthes crispus(S.crispus)ethanol leaves extract on the liver and kidney functions in Sprague Dawley rats.Methods:Young female rats aged between 8 and 12 week-old were randomly assigned into four groups with five animals each group(n=5).The first group served as control,while the second,third and fourth groups were orally treated with a single dose daily with 150 mg/kg,300 mg/kg,and600 mg/kg of S.crispus ethanol leaves extract for 14 d consecutively.Cage-side observation was conducted for first 4h after each dosing.The body weight changes,food consumptions and water intake were also recorded.Serum biochemical parameters,i.e.,aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,creatinine and urea were determined at Day15.All results were expressed as mean±SD and analysed using Dunnett's test.Results:It was obtained that 14-day oral administration of S.crispus ethanol leaves extract did not cause any adverse effects or lethality to the female Sprague Dawley rats,No significant changes in serum biochemical parameters,relative organs weights,body weights,food intake and water consumptions were observed between the treatment groups and control.Conclusions:In conclusion,14-day oral administration of S.crispus ethanol leaves extract was safe to be consumed in female rats without affecting the liver and kidney Functions.

Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes

BACKGROUND Type 1 diabetes(T1D),a chronic metabolic and autoimmune disease,seriously endangers human health.In recent years,mesenchymal stem cell(MSC)transplantation has become an effective treatment for diabetes.Menstrual bloodderived endometrial stem cells(MenSC),a novel MSC type derived from the decidual endometrium during menstruation,are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure,high proliferation rate and high immunomodulation capacity.AIM To comprehensively compare the effects of MenSC and umbilical cord-derived MSC(UcMSC)transplantation on T1D treatment,to further explore the potential mechanism of MSC-based therapies in T1D,and to provide support for the clinical application of MSC in diabetes treatment.METHODS A conventional streptozotocin-induced T1D mouse model was established,and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected.The morphological and functional changes in the pancreas,liver,kidney,and spleen were analyzed by routine histological and immunohistochemical examinations.Changes in the serum cytokine levels in the model mice were assessed by protein arrays.The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot.RESULTS MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice.Immunofluorescence analysis revealed that the numbers of insulin+and CD31+cells in the pancreas were significantly increased in MSC-treated mice compared with control mice.Subsequent western blot analysis also showed that vascular endothelial growth factor(VEGF),Bcl2,Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice.Additionally,protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferonγand tumor necrosis factorαand upregulated the serum levels of interleukin-6 and VEGF in the model mice.Additionally,histological and immunohistochemical analyses revealed that MSC transplantation systematically improved the morphologies and functions of the liver,kidney,and spleen in T1D model mice.CONCLUSION MenSC transplantation significantly improves the symptoms in T1D model mice and exerts protective effects on their main organs.Moreover,MSC-mediated angiogenesis,antiapoptotic effects and immunomodulation likely contribute to the above improvements.Thus,MenSC are expected to become promising seeding cells for clinical diabetes treatment due to their advantages mentioned above.

Influence of postural changes on haemodynamics in internal carotid artery bifurcation aneurysm using numerical methods

Cerebral intracranial aneurysms are serious problems that can lead to stroke,coma,and even death.The effect of blood flow on cerebral aneurysms and their relationship with rupture are unknown.In addition,postural changes and their relevance to haemodynamics of blood flow are difficult to measure in vivo using clinical imaging alone.Computational simulations investigating the detailed haemodynamics in cerebral aneurysms have been developed in recent times not only to understand the progression and rupture but also for clinical evaluation and treatment.In the present study,the haemodynamics of a patient-specific case of a large aneurysm on the left side internal carotid bifurcation(LICA)and no aneurysm on the right side internal carotid bifurcation(RICA)was investigated.The simulation of these patient-specific models using fluid–structure interaction provides a valuable comparison of flow behavior between normal and aneurysm models.The influences of postural changes were investigated during standing,sleeping,and head-down(HD)position.Significant changes in flow were observed during the HD position and quit high arterial blood pressure in the internal carotid artery(ICA)aneurysm model was established when compared to the normal ICA model.The velocity increased abruptly during the HD position by more than four times(LICA and RICA)and wall shear stress by four times(LICA)to ten times(RICA).The complex spiral flow and higher pressures prevailing within the dome increase the risk of aneurysm rupture.

Low-energy X-ray attenuation characteristics of Rhizophora spp.composites

Photon absorption parameters such as mass attenuation coefficients(μ_m),molar extinction coefficients(ε),total molecular(σ_(t,m)),atomic(σ_(t,a))and electronic(σ_(t,el))cross sections,half-value layers(X_(1/2)),tenth-value layers(X_(1/10)),mean free paths(λ),effective atomic numbers(Z_(eff)),and effective electron densities(N_(el))were estimated for defatted soy flour(DSF),soy protein concentrate(SPC),and soy protein isolate(SPI)-based Rhizophora spp.particleboard composites substituted with 10 wt%sodium hydroxide(NaOH)and 0,5,10,and 15 wt%itaconic acid polyamidoamine-epichlorohydrin(IA-PAE)adhesives.Elemental composition was assessed using ultrahigh-resolution field emission scanning electron microscopy-energy dispersive X-ray spectrometry(UHR-FESEM-EDX).The interaction parameters were evaluated for K_(α1)photons at16.59,17.46,21.21,and 25.26 keV,employing a low-energy germanium(LEGe)detector system and an~(241)Amγ-ray source.X-ray diffraction characterization revealed an amorphous phase in the developed particleboard composites.Samples DSF15',SPC15',and SPI15'exhibited the highest values ofμ_m,ε,σ_(t,m),Zeff,and N_(el)among all of the studied particleboard samples,within the range of measured photon energies.In addition,all of the modified samples exhibited lower X_(1/2),X_(1/10),λ,σ_(t,a),andσ_(t,el)than the unmodified samples,with DSF-,SPC-,and SPI/NaOH/Rhizophora spp./IA-PAE(15 wt%),indicating insignificant changes.The current results of the particleboard samples'analysis can be useful for medical radiation applications and shielding research.