The Impact Of Physicochemical Characteristics On Therapeutic Efficacy Of Anticancer Nanomaterials: A Review

Cancer is a global leading cause of death which suffers from treatment failures mainly due to intensive toxicity and lack of effectiveness of conventional drugs. The application of nanotechnology in cancer treatment promises to overcome the limitations of conventional drugs/drug delivery systems and improve their therapeutic efficacy. Materials at the nano scale possess novel properties that have an impact on their biological behaviour. The physiological interactions of nanomedicines in the body, which differ from those of conventional medicines, may provide benefits in pharmaceutical and/or clinical applications including, improvements in solubility, stability, efficacy, reduction of side effects, prevention and treatment of diseases. This paper discusses the unique characteristics and distinguished advantages of nanomaterials as anticancer drug carriers. Physicochemical properties of nanomaterials are critical parameters to their clinical translation. Hence, the impact of the main physicochemical properties on the efficacy of anitcancer nanomaterials, which are found to effective for cancer treatment and/or diagnosis, are presented. It is important to have reliable and robust characterization techniques that could enable relate physicochemical properties of nanomaterials with their in vivo behaviour. Brief explanation of the different techniques that can be used for studying the different physicochemical characteristics of nanomaterials is given. An important consideration, to achieve fast and successful development of nanotechnology-based anticancer drug products, is assessment and optimization of physicochemical and biopharmaceutical properties at the early stage. Obviously this requires collaboration among the different discovery and development scientists.

Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

Long-term efficacy of endovascular vs open surgical repair for complicated type-B aortic dissection: a single-center retrospective study and meta-analysis

This study aimed to evaluate the long-term survival and risk factors of traditional open surgical repair (OSR) vs thoracic endovascular aneurysm repair (TEVAR) for complicated type-B aortic dissection (TBAD). A total of 118 inpatients (45 OSR vs 73 TEVAR) with TBAD were enrolled from January 2004 to January 2015. Kaplan-Meier curves and Cox proportional hazards analysis were performed to identify the long-term survival rate and independent predictors of survival, respectively. Meta-analysis was used to further explore the long-term efficacy of OSR and TEVAR in the eight included studies using Review Manager 5.2 software. An overall 10-year survival rate of 41.9% was found, and it was similar in the two groups (56.7% OSR vs 26.1% TEVAR; log-rank P=0.953). The risk factors of long-term survival were refractory hypertension (OR=11.1; 95%CI=1.428-86.372; P=0.021] and preoperative aortic diameter >55 mm (OR=4.5; 95%CI=1.842-11.346; P=0.001). Long-term survival rate did not differ significantly between OSR and TEVAR (hazard ratio=0.87; 95%CI=0.52-1.47; P=0.61). Compared with OSR, TEVAR did not show long-term advantages for patients with TBAD. Refractory hypertension and total aortic diameter >55 mm can be used to predict the long-term survival of TBAD in the Chinese Han population.

Prevalence of genital human papillomavirus among rural and urban populations in southern Yunnan province, China

This study was designed to investigate and compare the HPV prevalence, genotypes distribution and associated risk factors in rural and urban women living in Xishuang Banna district, in the province of Yunnan. A total of 177 and 190 women from rural and urban areas were engaged, respectively. HPV DNA was amplified using the L1 consensus primers system (MY09/11 and GP5/6) and HPV GenoArray test was conducted for genotyping. Proportions were compared by chi-square test, and logistic regression was used to evaluate risk factors. A total of 54 women were positive for HPV DNA. Among rural women, 23 women were positive for HPV infection, of which 21 showed a single infection and 2 had a multiple infection. HPV-16 (10/23) was the most prevalent genotype followed by HPV-52 (5/23), and HPV-58 (5/23). Urban women had a higher infection rate for overall HPV (31/54) and for multiple genotype infection (8/31). HPV-52 (9/31) was the most prevalent genotype followed by HPV-39 (7/31) and HPV-68 (5/31). The age-specific HPV prevalence was also different between rural and urban women. In urban area, women with age <35 years had the highest HPV prevalence, which declined thereafter as age advanced. However, in rural women the highest HPV prevalence was observed in an older age group (>56 years). Ethnicity, smoking and parity were significantly associated with HPV infection among urban women. Our study demonstrates that HPV prevalence and genotype distribution varies among women from rural and urban areas in the south of Yunnan.

Development and application of Real-time PCR assay for detection of Theilera annulata infection in cattle in Xinjiang Uygur Autonomous Region, China

Theileria annulata (T. annulata), the causative agent of tropical theileriosis, is a protozoan parasite that also causes lymphoproliferative diseases in cattle. Development of reliable and fast methods are necessary in the epidemiological investigation of T. annulata in ticks and animals. Real-time PCR possesses merits of rapidity, accuracy, reliability, automation and ease of standardization, which is widely used for the detection of blood borne parasites. In this study, species-specific primers and TaqMan probe were designed on the basis of the 18s rRNA gene sequence of T. annulata, and the real-time PCR assay was developed by optimizing the reaction parameter. The performance of real-time PCR was assessed by testing 47 blood samples from cattle and comparing with the results from conventional PCR. The results show that this real-time PCR assay could specifically detect 10 copies DNA of T. annulata, which is 10-fold sensitivity more than conventional PCR. No cross-reactions were observed with Babesia bovis, Babesia bigemina, Trypanosoma evansi and Theileria equi. Of the 47 field samples collected from Xinjiang Uygur Autonomous Region, China, 36.17% were detected by real-time PCR, and 25.53% were found positive for T. annulata infection by conventional PCR. These results indicated that the real-time PCR assay is a useful approach for detecting T. annulata infections and has potential as an alternative tool for ecological and epidemiological surveillance of ovine theileriosis.

Myocardial remodeling and bioelectric changes in tachycardia-induced heart failure in dogs

In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.

The apolipoprotein E (APOE) gene and the risk of diabetic nephropathy (DN): a meta-analysis in East Asian populations

Background: Several studies have examined the association between DN and the APOE gene, but the results have been inconsistent. Objective: Determine whether APOE is a risk factor for DN by a meta-analysis. Methods: A meta-analysis was performed using all findings of 16 similar case–control studies in East Asian to evaluate the effect of APOE as a risk factor for DN. Several electronic databases were searched for relevant articles up to 2009. After data collection, a meta-analysis was used to assess heterogeneity, combine results and evaluate variations by using software STATA SE 9.0. Publication bias was examined by the Egger’s linear regression test and fail-safe number. Results: The meta-analysis showed that the ε2 allele almost doubled the risk of DN in East Asians (pooled ORs [95% CI]: 1.85 [1.49-2.29]). In contrast, studies relating the ε4 allele to DN risk were very heterogeneous and the pooled ORs were 1.05 [95% CI: 0.72-1.52]. In the subgroup meta-analysis, ε4 was substantially related to an increased risk for DN in studies conducted in China (pooled ORs [95% CI]: 1.51 [1.11-2.06]), which was different from previous results. However, the higher risk of DN associated with ε4 was not found in Japanese or Korean populations (pooled ORs [95% CI]: 0.46 [0.27-0.80] and 0.58 [0.09-3.55], respectively). Conclusion: The ε2 allele conferred a higher risk of DN in East Asians, and no significant result was obtained with the ε4 allele.

Desenvolvimento de um estimulador eletromagnético para promover consolidaçäo óssea / Development of an electromagnetic stimulator to promote bone consolidation

Fraturas ósseas näo consolidadas por mais de 6-9 meses säo muito preocupantes, já que as condutas terapêuticas tradicionais säo invasivas e têm baixa probabilidade de sucesso. Foi projetado e construído um estimulador eletromagnético capaz de gerar, através de um par de bobinas externas, um campo pulsátil no local da fratura, com o objetivo de promover e/ou acelerar a consolidaçäo. Este método visa substituir a estimulaçäo elétrica direta que, apesar dos bons resultados, apresenta riscos de infecçäo óssea por ser invasiva. Resultados clínicos preliminares com o protótipo construído säo encorajadores, embora uma avaliaçäo clínica mais extensiva e rigorosa seja necessária para comprovar a sua eficácia

Um modelo para desenvolvimento de infra-estrutura física para saúde / A model for the development of physical infrastructure for health

Após uma análise dos problemas da infra-estrutura física para saúde, um modelo conceitual é apresentado para orientar o seu desenvolvimento. Primeiro, os recursos materiais necessários devem ser deduzidos a partir de uma Política da Saúde pré-definida. Em seguida, o espaço físico e as instalaçöes precisam ser desenvolvidos numa seqüência lógica, partindo do planejamento preliminar e terminando na desativaçäo final. Paralelamente, a incorporaçäo de equipamentos médico-hospitalares deve ser planejada e programada considerando todas as etapas da sua vida útil. As possibilidades e as dificuldades de se implementar este säo discutidas

Molecular structure of troponin C from chicken skeletal muscle at 3Å resolution.

Troponin C is the Ca2+-binding subunit of the troponin complex and is involved in the calcium control of muscle contraction. The X-ray structure of chicken TnC has been determined at 3Å resolution using a single heavy atom derivative and application of a novel phase improvement and phase extension procedure. The protein has an unusual dumbbellshape with a length of about 70A. The N- and C-domains are connected by a single long α-helix of about 9 turns. Two metal binding sites (the Ca2+ -Mg2+ sites) in the C-domain are occupied by metal ions in the crystals and the helix-loop-helix Ca2+ -binding folds are very similar to those in other known Ca2+ -binding proteins. In contrast, the Ca2+ -specific sites in the N-domain appear unoccupied and the two putative Ca2+ -binding folds have a vastly different structural arrangement. The conformational rearrangements in the N-domain upon Ca2+ binding are believed to be the trigger for a cascade of protein-protein interaction alterations which lead to muscle contraction.