Mitochondrial carrier homolog 2 increases malignant phenotype of human gastric epithelial cells and promotes proliferation,invasion,and migration of gastric cancer cells

BACKGROUND The precise role of mitochondrial carrier homolog 2(MTCH2)in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated.AIM To determine the role of MTCH2 in gastric cancer.METHODS We collected 65 samples of poorly differentiated gastric cancer tissue and adjacent tissues,constructed MTCH2-overexpressing and MTCH2-knockdown cell models,and evaluated the proliferation,migration,and invasion of human gastric epithelial cells(GES-1)and human gastric cancer cells(AGS)cells.The mito-chondrial membrane potential(MMP),mitochondrial permeability transformation pore(mPTP)and ATP fluorescence probe were used to detect mitochondrial function.Mitochondrial function and ATP synthase protein levels were detected via Western blotting.RESULTS The expression of MTCH2 and ATP2A2 in gastric cancer tissues was significantly greater than that in adjacent tissues.Overexpression of MTCH2 promoted colony formation,invasion,migration,MMP expression and ATP production in GES-1 and AGS cells while upregulating ATP2A2 expression and inhibiting cell apoptosis;knockdown of MTCH2 had the opposite effect,promoting overactivation of the mPTP and promoting apoptosis.CONCLUSION MTCH2 can increase the malignant phenotype of GES-1 cells and promote the proliferation,invasion,and migration of gastric cancer cells by regulating mitochondrial function,providing a basis for targeted therapy for gastric cancer cells.

Elucidating the cardioprotective mechanisms of sodium-glucose cotransporter-2 inhibitors beyond glycemic control

Sodium-glucose cotransporter-2(SGLT2)inhibitors have emerged as a pivotal intervention in diabetes management,offering significant cardiovascular benefits.Empagliflozin,in particular,has demonstrated cardioprotective effects beyond its glucose-lowering action,reducing heart failure hospitalizations and improving cardiac function.Of note,the cardioprotective mechanisms appear to be independent of glucose lowering,possibly mediated through several mechanisms involving shifts in cardiac metabolism and anti-fibrotic,anti-inflammatory,and anti-oxidative pathways.This editorial summarizes the multifaceted cardiovascular advantages of SGLT2 inhibitors,highlighting the need for further research to elucidate their full therapeutic potential in cardiac care.

诱导胚胎干细胞分化为视网膜色素上皮细胞的培养方法

视网膜变性疾病导致视力下降,是视网膜色素上皮(RPE)细胞或感光细胞引起不可逆性损害或凋亡所造成的功能异常,从而导致的致盲性眼病,常引起视觉障碍甚至失明。人胚胎干细胞(hESCs)是一种能够多向分化的细胞。凭借适当的方法,hESCs可分化为各种视网膜细胞。由于人体RPE细胞无法再生,研究表明运用干细胞源性RPE细胞移植治疗视网膜病变的临床治疗方法具有实用前景,且近年来已取得突破性进展。多因素的限制、方法的选择以及诱导条件的复杂等使诱导分化RPE的效率和移植后存活率存在较大差异且不稳定,所以现阶段研究重点在于如何综合不同培养方法,取其利去其弊,提高hESCs定向分化效率以及细胞数量与质量,降低培养污染以及免疫排斥反应等。本文将对目前存在多种培养方法进行举例归纳总结,针对不同角度作出综述。

Therapeutic effect of Qingyi decoction in severe acute pancreatitis-induced intestinal barrier injury

AIM: To investigate the effect of Qingyi decoction onthe expression of secreted phospholipase A2(s PLA2) in intestinal barrier injury.METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into control, severe acute pancreatitis(SAP), Qingyi decoction-treated(QYT), dexamethasonetreated(DEX), and verapamil-treated(VER) groups. The SAP model was induced by retrograde infusion of 1.5% sodium deoxycholate into the biliopancreatic duct of the rats. All rats were sacrificed 24 h post-SAP induction. Arterial blood, intestine, and pancreas from each rat were harvested for investigations. The levels of serum amylase(AMY) and diamine oxidase(DAO) were determined using biochemical methods, and serum tumor necrosis factor(TNF)-α level was measured by an enzyme linked immunosorbent assay. Pathologic changes in the harvested tissues were investigated by microscopic examination of hematoxylin and eosinstained tissue sections. The expressions of s PLA2 at m RNA and protein levels were detected by reverse transcriptase PCR and Western blot, respectively. A terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was used to investigate apoptosis of epithelial cells in the intestinal tissues. RESULTS: Compared to the control group, the expression of s PLA2 at both the m RNA and protein levels increased significantly in the SAP group(0.36 ± 0.13 vs 0.90 ± 0.38, and 0.16 ± 0.05 vs 0.64 ± 0.05, respectively; P s < 0.01). The levels of AMY, TNF-α and DAO in serum were also significantly increased(917 ± 62 U/L vs 6870 ± 810 U/L, 59.7 ± 14.3 ng/L vs 180.5 ± 20.1 ng/L, and 10.37 ± 2.44 U/L vs 37.89 ± 5.86 U/L, respectively; P s < 0.01). The apoptosis index of intestinal epithelial cells also differed significantly between the SAP and control rats(0.05 ± 0.02 vs 0.26 ± 0.06; P < 0.01). The serum levels of DAO and TNF-α, and the intestinal apoptosis index significantly correlated with s PLA2 expression in the intestine(r = 0.895, 0.893 and 0.926, respectively; Ps < 0.05). Thelevels of s PLA2, AMY, TNF-α, and DAO in the QYT, VER, and DEX groups were all decreased compared with the SAP group, but not the control group. Qingyi decoction intervention, however, gave the most therapeutic effect against intestinal barrier damage, although the onset of its therapeutic effect was slower. CONCLUSION: Qingyi decoction ameliorates acute pancreatitis-induced intestinal barrier injury by inhibiting the overexpression of intestinal s PLA2. This mechanism may be similar to that of verapamil.

Hyperhomocysteinemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression

Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unclear. In this study, hyperhomocysteinemia was induced in apolipoprotein E-deficient mice with 1.7% methionine. Pathological changes in the olfactory bulb were observed through hematoxylin-eosin and Pischingert staining. Cell apoptosis in the olfactory bulb was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining. Transmission electron microscopy revealed an abnormal ultrastructure of neurons. Furthermore, immunoreactivity and expression of the hairy enhancer of the split 1 （Hesl） and Hess were measured using immunohistochemistry, immunofluorescence, and western blot assay. Our results revealed no significant structural abnormality in the ol- factory bulb of hyperhomocysteinemic mice. However, the number of TUNEL-positive cells increased in the olfactory bulb, lipofuscin and vacuolization were visible in mitochondria, and the expression of Hes1 and Hes5 decreased. These findings confirm that hyperhomocyste- inemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression.

Role of mitochondrial quality control in exercise-induced health adaptation

Long-term endurance training or physical activity has been confirmed not only to improve physical performance, but to bring about an obvious beneficial effect on human health; however, the mechanism of this effect is not clear. The most studied health adaptations in skeletal muscle response to endurance exercise are increased muscle glycogen level and insulin sensitivity, fiber type transformation toward oxidative myofibers, and increased mitochondrial content/function. Mitochondria are dynamic organelles in eukaryotic cells critical in physical performance and disease occurrence. The mitochondrial life cycle spans biogenesis, maintenance, and clearance. Exercise training may promote each of these processes and confer positive impacts on skeletal muscle contractile and metabolic functions. This review focused on the regulation of these processes by endurance exercise and discussed its potential benefits in health and disease. We presented evidence suggesting that exercise training potentiates not only the biogenesis of mitochondria but also the removal of old and unhealthy mitochondria through mitochondrial quality control.

Universal quantum circuit evaluation on encrypted data using probabilistic quantum homomorphic encryption scheme

Homomorphic encryption has giant advantages in the protection of privacy information.In this paper,we present a new kind of probabilistic quantum homomorphic encryption scheme for the universal quantum circuit evaluation.Firstly,the pre-shared non-maximally entangled states are utilized as auxiliary resources,which lower the requirements of the quantum channel,to correct the errors in non-Clifford gate evaluation.By using the set synthesized by Clifford gates and T gates,it is feasible to perform the arbitrary quantum computation on the encrypted data.Secondly,our scheme is different from the previous scheme described by the quantum homomorphic encryption algorithm.From the perspective of application,a two-party probabilistic quantum homomorphic encryption scheme is proposed.It is clear what the computation and operation that the client and the server need to perform respectively,as well as the permission to access the data.Finally,the security of probabilistic quantum homomorphic encryption scheme is analyzed in detail.It demonstrates that the scheme has favorable security in three aspects,including privacy data,evaluated data and encryption and decryption keys.

聚倍半硅氧烷以不同方式改性纤维素绝缘纸的机理研究

本文运用分子动力学方法,建立了纯纤维素模型和一系列聚倍半硅氧烷以不同方式改性的纤维素绝缘纸模型,并对其热力学性能进行了计算、对比和讨论.实验结果表明,各聚倍半硅氧烷纤维素改性模型的性能均优于未改性模型,并且当两条纤维素分子链作为取代基通过化学键接枝在聚倍半硅氧烷分子上(M2模型)时,改性效果最佳,其内聚能密度与溶解度参数的值相较于未改性模型提高了9%,拉伸模量、体积模量、剪切模量、柯西压的值分别提升了38.6%、29.5%、41.1%和29.5%,此外本文还计算并分析了各模型的自由体积分数和均方位移,结果显示,相较于其他模型,M2模型中的化学键在避免使纤维损失强度的同时,增加了分子链间的纠缠,使纤维素分子链占据了更多自由体积,从而使体系具有更小的自由体积分数,抑制了纤维素的链运动,进而提升了纤维素绝缘纸的热稳定性,这从微观角度解释了化学处理影响改性效果的机理.

Potential role of nimbolide in chemoprevention and therapy of prostate cancer

OBJECTIVE Prostate cancer is one of the most commonly diagnosed cancers worldwide.Current therapies for metastatic prostate cancer are only marginally effective,and hence novel treatment modalities are urgently needed.Considerable evidence suggests that chronic inflammation plays a pivotal role in the development and progression of prostate cancer.Thus agents that can suppress these inflammatory mediators could form the basis of novel therapy for prostate cancer patients.In our study,we focused on analyzing the potential anticancer effects of nimbolide,a terpenoid lactone derived from Azadirachta indica(Neem tree)against prostate cancer.METHODS Molecular biology techniques such as western blot analysis,DNA binding,luciferase assays,and immunohistochemistry were used for both in vitro and in vivo experiments.RESULTS Data from the in vitrostudies indicated that nimbolide could inhibit cell proliferation,induce apoptosis and suppress cellular invasion and migration.Interestingly,nimbolide also abrogated the activation of pro-inflammatory STAT 3 transcription factor,and this effect was found to be mediated via an increased production of reactive oxygen species(ROS),whereas depletion of ROS attenuated pSTAT 3 inhibitory effects of the drug.The in vivo efficacy of nimbolide was also noted in transgenic adenocarcinoma of mouse prostate(TRAMP)model,in which this triterpenoid significantly suppressed the tumor progression and growth without exhibiting any substantial adverse effects.CONCLUSION Overall our findings indicate that nimbolide exhibits significant anticancer effects in prostate cancer,and these effects may be mediated at least in part through the modulation of STAT 3 signaling pathway.

Alagille syndrome associated with total anomalous pulmonary venous connection and severe xanthomas:A case report

BACKGROUND Alagille syndrome(ALGS)is an autosomal dominant genetic disorder caused by mutations in the JAG1 or NOTCH2 gene.It is characterized by decreased intrahepatic bile ducts associated with a variety of abnormalities in many other organ systems,such as the cardiovascular,skeletal,and urinary systems.CASE SUMMARY We report a rare case of ALGS.A 1-month-old male infant presented with sustained jaundice and had a rare congenital heart disease:Total anomalous pulmonary venous connection(TAPVC).Sustained jaundice,particularly with cardiac murmur,caught our attention.Laboratory tests revealed elevated levels of alanine aminotransferase,aspartate aminotransferase,gamma-glutamyl transpeptidase,total bilirubin,and total bile acids,indicating serious intrahepatic cholestasis.Imaging confirmed the presence of butterfly vertebra at the seventh thoracic vertebra.This suggested ALGS,which was confirmed by genetic testing with a c.3197dupC mutation in the JAG1 gene.Ursodiol was administered immediately after confirmation of the diagnosis,and cardiac surgery was performed when the patient was 1.5 month old.He recovered well after treatment and was discharged at the age of 3 mo.At the age of two years,the patient returned to our clinic because multiple cutaneous nodules with xanthomas appeared,and their size and number increased over time.CONCLUSION We report a unique case of ALGS associated with TAPVC and severe xanthomas.This study has enriched the clinical manifestations of ALGS and emphasized the association between JAG1 gene and TAPVC.

A Secure Multiparty Quantum Homomorphic Encryption Scheme

The significant advantage of the quantum homomorphic encryption scheme is to ensure the perfect security of quantum private data.In this paper,a novel secure multiparty quantum homomorphic encryption scheme is proposed,which can complete arbitrary quantum computation on the private data of multiple clients without decryption by an almost dishonest server.Firstly,each client obtains a secure encryption key through the measurement device independent quantum key distribution protocol and encrypts the private data by using the encryption operator and key.Secondly,with the help of the almost dishonest server,the non-maximally entangled states are preshared between the client and the server to correct errors in the homomorphic evaluation of T gates,so as to realize universal quantum circuit evaluation on encrypted data.Thirdly,from the perspective of the application scenario of secure multi-party computation,this work is based on the probabilistic quantum homomorphic encryption scheme,allowing multiple parties to delegate the server to perform the secure homomorphic evaluation.The operation and the permission to access the data performed by the client and the server are clearly pointed out.Finally,a concrete security analysis shows that the proposed multiparty quantum homomorphic encryption scheme can securely resist outside and inside attacks.

STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia

Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology,and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types,including hematopoietic malignancy.However,acute myeloid leukemia(AML)is a heterogeneous disease and there is stll a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage.

基于天然高分子的导电材料制备及其在柔性传感器件中的应用

天然高分子材料具有来源广泛、化学成分多样、生物相容性和生物降解性良好等优势,是一类绿色可持续再生资源.近年来,基于天然高分子的绿色柔性传感器件研究受到了国内外学者的广泛关注,并取得了长足的进展.本文以天然高分子导电材料为主线,总结了基于天然高分子制备导电材料的模板法和掺杂法.模板法直接以天然高分子材料的天然骨架结构作为基质,而掺杂法以天然高分子材料处理后的产物或衍生物作为基质.归纳了基于天然高分子的柔性导电材料在湿度、温度、应变、气流/气体、光、生物传感器件中应用的研究进展,最后展望了基于天然高分子的柔性导电材料在设计和组装柔性传感器方面的前景,为高效发展绿色柔性电子和天然高分子材料的高值化利用提供新思路.