Light absorption distribution of prostate tissue irradiated by diffusing light source

Nitric oxide(NO)and nitric oxide synthase(NOS)have an important role in pain signaling transmission in animal models.Low-level laser therapy(LLLT)is known to have an analgesic effect,but the mechanism is unclear.The aim of the study is to investigate the influence of LLLT on NO release and NOS synthesis in dorsal root ganglion(DRG)neurons,in order to find whether LLLI can ameliorate pain through modulating NO production at the cellular level.The results show that in stress conditions,the laser irradiation at 658 nm can modulate NO production in DRG neurons with soma diameter of about 20μm in a short time after illumination,and affect NOS synthesis in a dose-dependent manner.It is demonstrated that LLLT might treat pain by altering NO release directly and indirectly in DRG neurons.     

老龄大鼠脑缺血再灌注海马神经元iNOS的表达及超微结构改变

目的：观察老年大鼠脑缺血再灌注后海马神经元诱导型一氧化氮合酶（induced nitric oxide synthase iNOS）的表达及超微结构变化。方法：建立老年大鼠不完全性全脑缺血动物模型，应用免疫组织化学染色和透射电镜，观察海马神经元iNOS的表达及超微结构变化。结果：缺血30min后再灌注24h组海马神经元iNOS活性显著升高；缺血30min再灌注21h和48h组中量表达；假手术组、缺血30min即刻取材、再灌注1h、6h、96h组iNOS几乎无表达；再灌注超过48h组海马神经元损伤较重。结论：NO是脑缺血后神经元迟发性死亡的重要因素之一。     

微波处理菘蓝种子的子叶发育与生物光子辐射的相关性

比较研究不同时间长度的微波辐照菘蓝种子对种子萌发率、淀粉酶活性、转氨酶活性、蛋白酶活性、蛋白质含量、游离氨基酸含量、总DNA含量、子叶发育状况及其生物光子辐射强度的影响.采用微波辐射浸泡3h的菘蓝(Isatis ind igotica Fort)种子.与对照相比,四种处理均能不同程度提高菘蓝种子萌发率、淀粉酶活性、转氨酶活性、蛋白酶活性,促进蛋白质、游离氨基酸、DNA合成,促进子叶发育,提高了生物光子辐射强度.低剂量微波辐射能提高种子生理生化代谢机能,促进种子萌发和幼苗生长发育,研究发现8 s微波预处理效果最为显著.     

他罗利姆对截肢大鼠NO和H2S的活化作用

目的观察大鼠截肢创伤应激后重要血管舒缩因子的变化及他罗利姆(FK506)对其调控作用,为截肢术后引起的远隔器官损伤的干预治疗提供依据。方法建立大鼠左后肢截肢创伤模型,将雄性Wistar大鼠80只随机分为10组:正常对照组、截肢后1h、2h、4h、6h、12h、24h、48h、72h组、他罗利姆干预组。测定血浆H2S、AngⅡ、NO的含量,心、肺、肝、肾组织CSE活性。结果与对照组比较,截肢创伤后1h血浆AngⅡ含量明显升高,于6h达峰值(684.497±77.515)pmol/L(P<0.05),72h恢复至正常水平;血浆NO、H2S截肢创伤后4h明显降低,6h达最低,分别为(8.553±0.896)μmol/L(P<0.05)、(55.654±6.332)μmol/L(P<0.05),24h恢复正常值。他罗利姆干预后,血浆H2S、NO,心、肺、肝、肾组织CSE活性较创伤6h组明显升高(P<0.05),血浆AngⅡ含量无明显变化。结论大鼠截肢创伤应激后血管收缩作用增强,他罗利姆主要升高血管舒张因子NO和H2S,对AngⅡ无明显调控作用。     

实验性慢性缺氧与肺血管结构的重建

目的：主要研究慢性缺氧与肺血管结构重建的关系,利用常压缺氧舱建立大鼠缺氧性肺动脉高压模型。实验动物分为3组：缺氧3天组、7天组、14天组。通过免疫组化的方法检测一氧化氮合成酶(NOS)的表达和含量,部分标本通过电镜观察。结果：在缺氧过程中,肺血管的胶原纤维明显增生,超微结构观察显示血管在早期可见内皮细胞损伤并伴有血小板性血栓形成;到后期出现肌纤维母细胞和胶原纤维增生。实验显示随缺氧时间的延长内皮细胞NOS的含量逐渐升高,而肺血管内源性的舒张反应反而降低,管腔狭窄,血流阻力加大。文中讨论了慢性缺氧与肺血管结构重建的关系,肺缺氧性肺动脉高压的机理,内皮细胞形态及功能的改变在肺动脉高压形成中的意义。     

高血压大鼠第四脑室外侧隐窝室管膜细胞超微结构变化的电镜观察

目的:观察一氧化氮(NO)缺乏型高血压大鼠,第四脑室外侧隐窝室管膜细胞及其分泌状态的超微结构变化.方法:30只健康雄性Wistar大鼠,其中20只予以一氧化氮合酶抑制剂左旋硝基精氨酸(L-NNA) 15 mg/d,腹腔注射,复制高血压动物模型;10只予以0.9%氯化钠2 mL/d腹腔注射作为对照.对照组、用药2周组和用...     

NO在CO2激光预处理提高小麦耐旱性中的作用

用CO2激光(20.1 mW/mm2)辐照小麦种子3 min,待其长至12天时,用质量浓度10%聚乙二醇6000(PEG6000)胁迫其幼苗,并通过添加NO的供体硝普钠(SNP)和血红蛋白(Hemoglobin,Hb;NO清除剂),研究NO在CO2激光预处理提高小麦耐旱性中的作用。结果表明,外源NO和激光预处理可使干旱胁迫的小麦幼苗丙二醛(MDA)含量显著降低(p<0.05),而超氧化物歧化酶(SOD),过氧化物酶(POD),过氧化氢酶(CAT)活性,叶绿素a,叶绿素b含量和根干重却显著增加(p<0.05)。而经过适当剂量激光辐照干旱胁迫小麦幼苗再加外源血红蛋白(Hb,NO清除剂)处理则没有这种作用。     

龙胆苦苷对脓毒症小鼠急性肝损伤的保护作用

目的:研究龙胆苦苷对脓毒症致急性肝损伤小鼠的保护作用.方法:采用盲肠结扎穿孔(Cecal ligation and puncture,CLP)诱导形成脓毒症小鼠急性肝损伤模型.40只昆小鼠随机分为四组,分别为假手术组、CLP模型组、CLP+龙胆苦苷(25 mg/kg、50m/kg)治疗组.记录一般情况并检测CLP术后12h各组小鼠血清中肿瘤坏死因子α(TNF-α)、白介素6(IL-6)的含量,谷丙转氨酶(ALT)、谷草转氨酶(AST)活性以及肝脏组织中一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)、丙二醛(MDA)和髓过氧化物酶(MPO)水平,光学显微镜观察各组小鼠肝脏组织的病理变化情况.结果:龙胆苦苷呈剂量依赖性的降低脓毒症小鼠血清中炎症因子(TNF-α、IL-6)、ALT及AST含量,降低肝组织NO和MDA含量及iNOS和MPO活性,病理切片显示龙胆苦苷治疗组肝脏组织病理损伤情况均较模型组减轻.结论:龙胆苦苷对CLP诱导的小鼠急性肝损伤具有一定的保护效应,其作用可能与抑制炎症反应及抗氧化作用有关.     

电针足三里对脓毒症大鼠促炎症因子所致心肌损伤的保护作用

目的研究电针足三里穴(ST36)对脓毒症大鼠促炎症因子所致心肌损伤的保护作用。方法雄性SD大鼠32只,采用盲肠结扎穿孔术(CLP)制备大鼠脓毒症模型,随机分为电针(Electro-Acupuncture,EA)足三里组(EA组)、CLP+假电针(ShameEA)组(SEA组)、迷走神经切断(Vagotomy,VA)+CLP组(VA组)和迷切后CLP再电针组(VA/EA组)4组,每组8只。EA组持续针刺双侧足三里穴1h(2mA,2-100Hz);SEA组采用相同频率和强度刺激非经非穴(足三里穴外侧旁开0.5cm)。VA组先切断腹腔迷走神经再施行CLP术。各组大鼠于CLP术后6h,取血检测血浆肌酸激酶同工酶(CK-MB)活性;然后处死动物,取心肌组织,测定肿瘤坏死因子-α(TNF-α)水平、一氧化氮(NO)含量、随过氧化物酶(MPO)活性以及组织含水率。结果CLP术后6h,EA组心肌组织促炎症因子TNF-α、NO、MPO水平、CK-MB活性以及组织含水率均显著低于其余3组(P<0.05);VA/EA组和VA组TNF-α、NO、MPO水平、CK-MB活性及组织含水率均高于SEA组(P<0.05);VA/EA组与VA...     

低强度激光照射对离体家兔红细胞膜磷脂成分及电泳率的影响

目的:探讨低强度激光对离体家兔红细胞膜磷脂成分及电泳率的影响.方法:用低强度激光照射家兔红细胞和血小板,以薄层色谱扫描法和显微(细胞)电泳法测定.结果:实验组红细胞膜磷脂成分中磷脂酰胆碱显著增多(p＜0.01),而鞘磷脂类、磷脂酰乙醇胺都程度不同的减少(p＜0.05),特别是磷脂酰丝氨酸含量、鞘磷脂类/磷脂酰胆碱及磷脂酰丝氨酸/磷脂酰胆碱比值显著减小(p＜0.01).血小板及红细胞的电泳率显著高于对照组.结论 低强度激光照射可改变离体家兔红细胞膜磷脂成分和电泳率.     

Robust Organoalkoxysilanes as Red Unconventional Fluorescent Platform

Unconventional fluorescent materials have attracted intense and continuous attention due to the facile processability, excellent biocompatibility, and high availability. However, for the lack of suitable unconventional fluorescent platform, unconventional luminophore‐based fluorescent probes have not been applied in the biological field, especially in the detection of bioactive molecules. In this work, unconventional red fluorescence is observed from a series of organoalkoxysilanes for the first time. Particularly, the unique fluorescence derived from smart Si–O bridged structures prompt the fluorescent probe design strategy. The strategy involves applying the Si–O bridge to provide desirable red unconventional fluorescence, and ratiometric detection of endogenous nitric oxide in lysosomes and in vivo. It is expected that this novel strategy will expand the applications of unconventional fluorescence to the bioimaging field, and further provide valid approach for the future evolution of unconventional fluorescent probes.     

Poly(cyclodextrin)‐Polydrug Nanocomplexes as Synthetic Oncolytic Virus for Locoregional Melanoma Chemoimmunotherapy

Despite the approval of oncolytic virus (OV) therapy for advanced melanoma, its intrinsic limitations that include the risk of persistent viral infection and cost‐intensive manufacturing motivate the development of analogous approaches that are free from the disadvantages of virus‐based therapies. Herein, reported is a nanoassembly comprised of multivalent host–guest interactions between polymerized paclitaxel (pPTX) and nitric oxide‐incorporated polymerized β‐cyclodextrin (pCD‐pSNO) that through its bioactive components and when used locoregionally recapitulates the therapeutic effects of OV. The resultant pPTX/pCD‐pSNO exhibits significantly enhanced cytotoxicity, immunogenic cell death, dendritic cell (DC) activation, and T cell expansion in vitro compared to free agents alone or in combination. In vivo, intratumoral administration of pPTX/pCD‐pSNO results in activation and expansion of DCs systemically, but with a corresponding expansion of myeloid‐derived suppressor cells and suppression of CD8⁺ T cell expansion. When combined with antibody targeting cytotoxic T lymphocyte antigen‐4 that blunts this molecule's signaling effects on T cells, intratumoral pPTX/pCD‐pSNO treatment elicits potent anticancer effects that significantly prolong animal survival. This formulation thus leverages the chemo‐ and immunotherapeutic synergies of PTX and nitric oxide and suggests the potential for virus‐free nanoformulations to mimic the therapeutic action and benefits of OVs.     

Multiwalled Carbon Nanotubes Induced Hypotension by Regulating the Central Nervous System

Cardiovascular disease is the leading cause of death worldwide. Normal blood pressure is very important for overall well‐being and unexpected decrease in blood pressure may cause many detrimental consequences. The attractive properties of multiwalled carbon nanotubes (MWCNTs) entice their usage in many cutting edge brain‐specific therapies. However, the effects of MWCNTs to the central nervous system are not fully understood. In this work, the authors report that carbon nanotubes can significantly cause blood pressure to fall down when introduced into the brain at very low dosage. It is found that MWCNTs induce increased expression of neuronal nitric oxide synthase in the medulla cardiovascular center, which consequently attenuate sympathetic nerve activity and cause decrease in blood pressure and heart rate. In addition, MWCNTs promote acetylation and nuclear translocation of nuclear factor‐κB in brain cells. This work illustrates how CNTs can potentially change blood pressure by interrupting the central nervous system and is significant to the biomedical applications of CNTs.     

Nitric Oxide Modulating Calcium Store for Ca2+-Initiated Cancer Therapy

Ions are essential to body, but sometimes can evolve into weapons to attack and destroy cells without systematic toxicity and drug resistance. Inspired by nitric oxygen as neurotransmitter in mediating Ca²⁺ release, NO nanodonors with high photoreactivity and stability are constructed with upconversion nanoparticles (UCNPs) coated by zeolitic nitro-/nitrile-imidazole framework-82 (ZIF-82), capable of near-infrared light (NIR) triggered NO generation and berbamine (BER) release, to achieve cancer therapy with the stored Ca²⁺ in cells. The spatial confinement effect of 2-nitroimidazole in ZIF-82 enables NO-releasing with tunable release kinetics. NO turns on the ryanodine receptors overexpressed in cancer cells for abrupt Ca²⁺ elevation; meanwhile, berbamine (BER) turns Ca²⁺-excretion pumps off to inhibit calcium efflux, resulting in intracellular Ca²⁺ overload induced apoptosis. This work provides the first example of regulating endogenous ions for cell killing, which holds promise as an effective cancer therapeutics that is complementary to traditional chemotherapeutics.     

Four Birds with One Stone: A Multifunctional Polypeptide Nanocomposite to Unify Ferroptosis,Nitric Oxide,and Photothermia for Amplifying Antitumor Immunity

Tumor metastasis and relapse mainly results in therapy failure and becomes a big challenge in oncology. Immunogenic cell death (ICD) of tumors mediated immunotherapy (IT) is attracting widely for solving that problem although achieving sufficient ICD and strong immune response is challenging for nanoparticles-based cancer IT. Herein, a multifunctional polypeptide coordinate nanocomposite that possesses near infrared photothermia (PT) and responsive releases of nitric oxide (NO) and iron ions is constructed, which synergistically kills cancer cells and highly prohibits metastatic 4T1 cells invasion and migration by PT-boosted NO release and ferroptosis (FT). Remarkably, triple FT-NO-PT treatment amplifies the ICD effects and outperforms combo/monotherapy FT-PT and FT in cancer cells and tumors, which further activates dendritic cells maturation, and primed CD4⁺T and CD8⁺T cells immune responses and memory effects, playing four birds with one stone (i.e., FT-NO-PT-IT). The PCSFG-based FT-NO-PT not only fully eradicates 4T1 primary tumors, but also induces strong ICD, immune priming, and memory effects to reject rechallenged 4T1 tumors and inhibit malignant tumor metastasis, demonstrating synergistic amplified ICD effects with strong cell immunities and memory effects by a unified FT-NO-PT-IT.     

A Tunable,Stable, and Bioactive MOF Catalyst for Generating a Localized Therapeutic from Endogenous Sources

The versatile chemical and physical properties of metal organic frameworks (MOFs) have made them unique platforms for the design of biomimetic catalysts, but with only limited success to date due to instability of the MOFs employed in physiological environments. Herein, the use of Cu(II)1,3,5‐Benzene‐tris‐triazole (CuBTTri) is demonstrated for the catalytic generation of the bioactive agent nitric oxide (NO) from endogenous sources, S‐nitrosothiols (RSNOs). CuBTTri exhibits structural integrity in aqueous environments, including phosphate buffered saline (76 h, pH 7.4, 37 °C), cell media used for in vitro testing (76 h, pH 7.4, 37 °C), and fresh citrated whole blood (30 min, pH 7.4, 37 °C). The application of CuBTTri for use in polymeric medical devices is explored through the formation of a composite CuBTTri‐poly by blending CuBTTri into biomedical grade polyurethane matrices. Once prepared, the CuBTTri‐poly material retains the catalytic function towards the generation of NO with tunable release kinetics proportional to the total content of CuBTTri embedded into the polymeric material with a surface flux corresponding to the therapeutic range of 1–100 nm cm^?2 min^?1, which is maintained even following exposure to blood.     

A Mixed Component Supramolecular Hydrogel to Improve Mice Cardiac Function and Alleviate Ventricular Remodeling after Acute Myocardial Infarction

Myocardial infarction (MI) remains the major cause of death and disability in the world, and intramyocardial administration of biomaterials (e.g., hydrogels) along the perimeter of MI region is demonstrated as an effective way for the treatment of MI. The curcumin has anti‐inflammation, antioxidation, and antiapoptosis properties, and nitric oxide (NO) molecules are favorable for angiogenesis. This study prepares a mixed component hydrogel capable of releasing both bioactive curcumin and NO for the treatment of MI. The study shows that the combinational treatment of curcumin and NO can remarkably reduce collagen deposition, improve cardiac function, ameliorate adverse myocardium remodeling, suppress apoptosis, and hypertrophy as well as attenuate the expression of matrix metalloproteinases (MMPs) and transforming growth factor‐β1 (TGF‐β1) and upregulate the expression of silent information regulator 1 than curcumin alone, because of the synergistic action of both molecules and the angiogenesis promotion ability of NO. The results indicate that codelivery of curcumin and NO in a controllable manner by hydrogels might be considered as a promising option for treatment of cardiovascular disease.     

微孔板荧光观察一氧化氮影响癌细胞线粒体膜电位

利用微孔板荧光分析仪结合线粒体膜电位特异性荧光探针罗丹明123测量了内外源性一氧化氮对癌细胞线粒体膜电位的影响。实验结果显示添加一氧化氮供体后,荧光强度快速增大,且在较长的一段时间内保持不变,而对照组的荧光强度没有明显变化;此外,加载荧光探针前用一氧化氮合酶抑制剂和一氧化氮供体孵育24 h分别能降低和提高线粒体膜电位。研究结果表明增加内外源性一氧化氮均能提高线粒体膜电位,这对于在细胞器水平认识一氧化氮参与促进癌细胞增殖与转移的过程具有一定的意义。     

Polymer‐Based Nitric Oxide Therapies: Recent Insights for Biomedical Applications

Since the discovery of nitric oxide (NO) in the 1980s, this cellular messenger has been shown to participate in diverse biological processes such as cardiovascular homeostasis, immune response, wound healing, bone metabolism, and neurotransmission. Its beneficial effects have prompted increased research in the past two decades, with a focus on the development of materials that can locally release NO. However, significant limitations arise when applying these materials to biomedical applications. This Feature Article focuses on the development of NO‐releasing and NO‐generating polymeric materials (2006–2011) with emphasis on recent in vivo applications. Results are compared and discussed in terms of NO dose, release kinetics, and biological effects, in order to provide a foundation to design and evaluate new NO therapies.     

Luminescent Metal‐Organic Frameworks for Selectively Sensing Nitric Oxide in an Aqueous Solution and in Living Cells

Cu²⁺‐based metal‐organic framework (Cu? TCA ) (H₃ TCA = tricarboxytriphenyl amine) having triphenylamine emitters was assembled and structurally characterized. Cu? TCA features a three‐dimensional porous structure consolidated by the well‐established Cu₂(O₂CR)₄ paddlewheel units with volume of the cavities approximately 4000 nm³. Having paramagnetic Cu²⁺ ions to quench the luminescence of triphenylamine, Cu? TCA only exhibited very weak emission at 430 nm; upon the addition of NO up to 0.1 mM , the luminescence was recovered directly and provided about 700‐fold fluorescent enhancement. The luminescence detection exhibited high selectivity – other reactive species present in biological systems, including H₂O₂, NO₃^?, NO₂^?, ONOO^?, ClO^? and ¹O₂, did not interfere with the NO detection. The brightness of the emission of Cu? TCA also led to its successful application in the biological imaging of NO in living cells. As a comparison, lanthanide metal‐organic framework Eu? TCA having triphenylamine emitters and characteristic europium emitters was also assembled. Eu? TCA exhibited ratiometric fluorescent responses towards NO with the europium luminescence maintained as the internal standard and the triphenylamine emission exhibited more than 1000‐fold enhancement.