A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.     

Bio-accumulation and health risk assessment of heavy metals in different edible fish species from Hurghada City,Red Sea,Egypt

BackgroundHeavy metal contamination has become a serious issue in this century especially detected in fish organs. Due to the presence of radioactive compounds in agricultural and sewage effluent, which destroys aquatic ecosystems, threatening human livelihoods. Health hazards associated with low and high consumption consumers assessed in five commercial fish species collected from Hurghada City, Egypt, during winter and summer, 2020. Atomic absorption spectrophotometer technique used for determination heavy meals in different organs and expressed as μg/g wet weight.ResultsHeavy metal concentrations in muscle ranged between:(0.054–0.109), (0.260–1.043), (0.264–0.897), (5.895–11.898), (0.381–0.970), (13.582–29.133) and (0.332–0.589) µg/g for Cd, Pb, Mn, Zn, Cu, Fe and Ni respectively, which were lower than those of gills and liver. These concentrations were within WHO, FAO/WHO, and EU standards. Consumption of edible species was lower than the (TDIs) established by the (JECFA) and Egyptian Standards. Even though THQ and TTHQ values were < 1 while, in children with highly consumer were> 1.ConclusionThis study concluded that intake of Red Sea fish is safe for human health. It is critical for consumers to be aware of the consequences of excessive fish consumption, particularly children with highly consumer, which represent possible health risks.     

Editorial Commentary: Stabilize the Patella to Achieve Functional Gain but Don’t Neglect the Cartilage That May Cause Long-Term Pain! Trochlear Dysplasia Plays a Role in Both

While trochlear dysplasia is commonly discussed as a major risk factor for recurrent patellar instability, it also has a strong relationship with the development of patellofemoral cartilage lesions. Patellofemoral instability frequently occurs in teens and young adults, and the high prevalence of associated cartilage damage unfortunately sets patients up for the progression of degenerative changes of the patellofemoral joint at an early age. The judicious use of magnetic resonance imaging can help identify the presence of chondral lesions, allowing for urgent management of associated osteochondral fractures or open discussions and patient education about the possibility of performing a cartilage restoration procedure concurrently with patellar stabilization surgery. The location and presence of patellofemoral chondral lesions should be considered when contemplating the concurrent use of tibial tubercle osteotomy as part of the patellar stabilization procedure.     

中药降香的本草考证

降香为我国传统中药材,历代本草对其记载较为混杂,至今基原仍存在较大争议。从名称、基原、产地、品质评价、采收加工及炮制方面进行考证可知,降香本名降真香,历代本草中多以降真香为正名记载,自明代《本草纲目》将降香作为降真香的简称,后至清末、民国时期逐渐以降香作为药材正名。从古至今降香基原历经变革,古代（1840年前）国产降香基原考证为黄檀属藤黄檀Dalbergia hancei Benth.、斜叶黄檀D. pinnata （Lour.） Prain、两粤黄檀D. benthamii Prain、滇黔黄檀D. yunnanensis Franch.等能够产生香材的藤本植物,进口降香基原则考证为黄檀属印度黄檀D. sissoo DC.、小花黄檀D. parviflora Roxb.等具有心材的木本植物;由于降真香（山油柑）Acronychia pedunculata （L.） Miq.植物名与药材名相同,1840—1948年部分著作误将山油柑作降香记载;《中华人民共和国药典》1977年版首次收录降香,规定其基原为降香檀D. odorifera T. Chen。据记载,古代国产和进口降香均无明确道地产区;1949年至今,唯一道地产区为海南省。历代本草记载,进口降香以颜色红且香气甜而不辣,或颜色紫而油润者入药为佳;中华人民共和国成立后,以降香檀心材替代进口降香入药,其品质以颜色紫红、质地坚硬油润者为佳。历代本草记载降香炮制方法包括将其刮下碾成细末和烧存性;近现代以加工成细粉或镑片为主。考证结果为今后成方制剂开发及临床应用提供重要参考。     

药用植物金荞麦中黄酮类化合物积累的时空变化规律

目的 探究药用植物金荞麦不同生育期各器官中黄酮类化合物积累的时空分布规律,为金荞麦合理采收、资源化利用和高价值开发提供科学依据。方法 以根茎繁殖不同生长年限的金荞麦为研究对象,在不同生育时期采集根、茎、叶、花器官,采用高效液相色谱法测定各器官样品中儿茶素、表儿茶素、芦丁和总黄酮含量。结果 随着金荞麦生育期推进,植株不同器官的黄酮类化合物积累增加,以秋季地上部分枯萎后的含量最高;不同生育时期叶片中的儿茶素、表儿茶素、芦丁和总黄酮含量均显著高于根茎和茎秆（P<0.05）。不同器官间儿茶素、表儿茶素、芦丁和总黄酮含量差异有统计学意义（P<0.05）,花中儿茶素、芦丁和总黄酮含量最高;表儿茶素含量在茎秆中最低。黄酮类物质含量在根茎不同部位差异有统计学意义（P<0.05）,表儿茶素和总黄酮含量在根茎不同组织部位表现为须根>韧皮部>根茎（不含须根）>木质部（P<0.05）,儿茶素和芦丁分别在须根和韧皮部含量最高。1年生与2年生金荞麦植株不同器官的黄酮类化合物含量差异无统计学意义。结论 在不考虑产量的前提下,根茎繁殖金荞麦种植1年即可采收,适宜采收期为11月上旬。     

北柴胡β-香树脂醇合酶基因家族成员鉴定及功能验证

目的 从转录组层面对北柴胡Bupleurum chinense β-香树脂醇合酶（β-amyrin synthase,β-AS）基因家族成员进行鉴定,并对其表达及功能进行分析验证,以期为解析柴胡皂苷的合成和调控提供基础。方法 基于全长转录组数据挖掘北柴胡β-AS基因家族成员（BcBASs）,利用在线软件对各基因进行生物信息学分析,利用大肠杆菌和烟草验证关键基因的功能。结果 从北柴胡转录组数据中挖掘到不冗余的β-AS基因6个,可分为3个亚家族,它们都具有典型保守区域DCTAE、MWCYCR和QW。进化分析表明,BcBAS1、BcBAS2、BcBAS4、BcBAS5、BcBAS6可能为单功能β-AS基因,BcBAS3可能为多功能β-AS基因,表达分析表明各基因在根和叶中的表达模式有差异。在大肠杆菌中成功表达了BcBAS1可溶性重组蛋白,相对分子质量约87 000,烟草瞬时表达表明BcBAS1编码蛋白具有β-AS功能,能促进β-香树脂醇的积累。结论 对北柴胡中6个不冗余的β-AS基因家族成员进行了鉴定和生物信息学分析,获得了BcBAS1可溶性重组蛋白,在烟草中验证了BcBAS1为有功能的β-AS,为柴胡皂苷合成调控机制和生物合成研究奠定了基础。     

硬尖神香草的化学成分研究

目的 研究硬尖神香草Hyssopus cuspidatus地上干燥部分的化学成分。方法 采用硅胶柱色谱、高效液相色谱技术等进行分离纯化,通过现代波谱学技术对所得化合物进行结构鉴定,并采用MTT比色法对分离得到的化合物进行体外抑制人胃癌HGC-27细胞的活性筛选。结果 从神香草95%乙醇提取物中分离得到9个化合物,分别鉴定为4S-(2-羟基异丙基)-环己烷-2-烯-1-酮（1）、(3R,4aR,5R,6R)-6-羟基-4a,5-二甲基-3-(丙-1-烯-2-基)-3,4,4a,5,6,7-六氢萘-1(2H)-酮（2）、对茴香酸（3）、三裂鼠尾草素（4）、5-羟基-6,7,3'',4''-四甲氧基黄酮（5）、蓟黄素（6）、E-p-香豆醇乙醚（7）、(E)-p-香豆醇γ-O-甲醚（8）、4-羟基-3-甲氧基乙基肉桂酸盐（9）。其中,化合物1为新化合物,命名为神香草酮A。对化合物1～9进行抗肿瘤活性筛选,结果显示,化合物1、3、8对HGC-27胃癌细胞具有一定的抑制作用,其半数抑制浓度（median inhibition concentration,IC₅₀）值分别为8.76、16.34、25.28 μmol/L。结论 化合物1为新化合物,化合物5～9为首次从该属植物中分到。     

Relationships between anthropometric adiposity indexes and bone mineral density in a cross-sectional Chinese study

Background ContextPrevious studies have reported conflicting results for the relationships between anthropometric adiposity indexes and bone mineral density, based on dual-energy X-ray absorptiometry (DXA). However, few studies were published based on quantitative computed tomography (QCT), especially for Chinese population.PurposeTo evaluate the associations of spine bone mineral density (BMD) with body mass index (BMI), waist circumstance (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and a body shape index (ABSI) using QCT.Study Design/SettingA Cross-sectional study.Patient SampleAround 3,457 participants in multiple communities across 7 administrative regions of China.Outcome MeasuresSpine BMD was measured using QCT, and the classification of osteoporosis was defined as follows: 1) osteoporosis if BMD <80mg/cm³, 2) osteopenia if BMD 80–119 mg/cm³, and 3) normal bone mass if BMD≥120 mg/cm³.MethodsThis study was conducted using convenient sampling between 2013 and 2017. Multivariable linear regression model and logistic regression models were used for the associations of continuous and categorical BMD, respectively.ResultsAround 3,405 participants were included in the final analyses, including 1,272 males and 2,133 females, with spine BMD of 111.00±35.47 mg/cm³ and 99.38±40.60 mg/cm³, respectively. Spine BMD decreased significantly with the increase of ABSI in females (adjusted β, ?5.74; 95% confidence interval [CI], ?8.50 to ?2.98), and this trend also was kept in females aged at less than 60 years (adjusted β, ?14.54; 95% CI, ?20.40 to ?8.68), and females with age ≥60 years (adjusted β, ?7.59; 95% CI, ?10.91 to ?4.28). However, this inverse association was observed only in males with age ≥ 60 years (adjusted β, ?5.19; 95% CI, ?10.08 to ?0.29). Except ABSI, negative associations of Spine BMD with WC (adjusted β, ?0.46; 95% CI, ?0.77 to ?0.15), WHR (adjusted β, ?6.25; 95% CI, ?10.63 to ?1.86), WHtR (adjusted β, ?6.80; 95% CI, ?11.63 to ?1.97) were shown in females aged at <60 years, and positive association with BMI in males with age ≥60 years (adjusted β, 0.92; 95% CI, 0.29–1.55).ConclusionsABSI had more remarkable association with spine BMD, compared with the other four indexes.