Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning

Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.

Fator capacidade de fósforo em solos de pernambuco mineralogicamente diferentes e influência do pH na capacidade máxima de adsorção / Phosphate capacity factor in mineralogically different soils in Pernambuco and the influence of pH on the maximum capacity of adsorption

O Fator Capacidade de Fósforo (FCP) é definido pela razão de equilíbrio entre o fator quantidade de P (Q) e o fator intensidade (I) e representa uma medida da capacidade do solo em manter um determinado nível de P em solução. As características e o teor dos constituintes minerais da fração argila são responsáveis por uma maior ou menor FCP, interferindo nas relações solo-planta. Por outro lado, o pH do solo tem, em alguns casos, mostrado-se com efeito na adsorção e, em outros, com pequena e não consistente alteração na Capacidade Máxima de Adsorção de P (CMAP). Objetivou-se, neste trabalho, determinar o FCP de solos mineralogicamente diferentes em Pernambuco; correlacionar características físicas e químicas dos solos com o FCP; e avaliar o efeito do pH na CMAP. Amostras subsuperficiais de quatro solos, mineralogicamente diferentes, foram caracterizadas química e fisicamente e determinado o FCP. Essas amostras foram corrigidas com CaCO3 e MgCO3 na proporção 4:1 e incubadas por 30 dias, com exceção do Vertissolo. Determinou-se a CMAP antes e após a correção dos solos. O experimento consistiu de um fatorial 4 x 2 (quatro solos com e sem correção), distribuídos em blocos ao acaso, com três repetições. As características dos solos que melhor refletiram o FCP foram o P remanescente (P-rem) e a CMAP. Independentemente dos constituintes mineralógicos da fração argila, solos com elevados teores de alumínio apresentaram aumento da CMAP com a correção. A energia de adsorção (EA) nos solos corrigidos foi, em média, significativamente menor, independentemente do solo.

Phosphate Maximum Capacity (FCP) is defined by the ratio of equilibrium between the amount of factor P (Q) and factor intensity (I) and represents a measure of the soil ability to maintain a certain level of P in solution. The characteristics and content of the constituents of clay minerals are responsible for a greater or lesser FCP, interfering in soil-plant relations. Moreover, the soil pH has affected adsorption, and in other cases, it has shown small and inconsistent change in the maximum adsorption capacity of P (CMAP). Thus, this study aimed to determine the different FCP soil mineralogy in Pernambuco; to correlate physical and chemical characteristics of soils with PBC and to evaluate the effect of pH on the CMAP. Subsurface soil samples from four different soils were characterized chemically and physically determined, and the PBC was determined. These samples were corrected with CaCO3 and MgCO3 in a 4:1 ratio and incubated for 30 days, except the Vertisol. The CMAP was determined before and after correction of the soil. The experiment consisted of a 4 x 2 factorial (four soils with and without correction), distributed in randomized blocks with three replicates. Soil characteristics that best reflected the PBC were the remaining P (P-rem) and MPAC. Regardless of the constituents of clay mineralogy, soil with high aluminum levels had increased CMAP after correction. The energy of adsorption (EA) in the limed soils was on average significantly lower, regardless of the soil.

Long-term Postoperative Follow-up of Carpal Tunnel Syndrome with Undetectable APB-CMAP / The Japanese Journal of Rehabilitation Medicine

This study assessed the predictability of postoperative recovery of thumb opposition in patients with carpal tunnel syndrome and undetectable compound muscle action potential of the abductor pollicis brevis (APB-CMAP). Thirty-seven hands of 33 patients with a mean age of 59.8 years old were reviewed one year or longer after carpal tunnel release surgery, with a mean follow-up period of 39 months. Thenar muscle atrophy had disappeared in 21 hands (57%), all of which had detectable APB-CMAPs. Thenar muscle atrophy persisted in 16 hands (43%), among which APB-CMAPs were detectable in 7 hands and remained undetectable in 9 hands. Disease duration preceding surgery did not differ significantly between the hands in which muscle atrophy disappeared and the hands in which muscle atrophy persisted. Thenar atrophy disappeared in all seven patients under 50 years of age at the time of carpal tunnel release, but persisted in 16 of the 30 (53%) patients over 50 years of age. These findings indicate that good recovery of thumb opposition can be expected without opponensplasty in patients less than 50 years of age. However, recovery was not predictable in patients over 50 years of age.

Simvastatin effect on inhibiting of the production of serum IL-6 and promotion the regeneration of sciatic nerve of rats / 中国矫形外科杂志

[Objective]To study the effect of Simvastatin on the regeneration of sciatic nerve of rats and its mechanism of immunoregulation.[Method]Twenty eight female Sprague-Dawley rats were used and the rats experienced the sciatic nerve crush injury.Animals were randomized into: Simvastatin-treated crush injury animals,vehicle-treated crush injury animals and sham-operated animals.Simvastatin(20 mg/kg) was given once a day over a time period of 14 day sby oral gavage via a pharyngeal tube.After surgery,the functional evaluation of nerve recovery,electrophysiologic assessment,histological assessment,serum IL-6 and TNF-? assessment were performed.[Result]The toe spread index of Simvastatin-treated crush injury animals was higher significantly than that of vehicle rats at d5 and d8(P

Titration of Phenol Nerve Block Effects on Peripheral Nerves: Electrophysiologic and Mechanical Measurements

OBJECTIVE: The purpose of this study was to titrate the nerve block effect of phenol with different concentrations of phenol solution by electrophysiological and mechanical measurements. METHOD: Right tibial nerves of twenty three adult rabbits were blocked by phenol solution with different concentrations (3%, 5%). Nerve conduction study for compound muscle action potential (CMAP), tension by electrical stimulation, and stiffness (slope) of stretch reflex of the triceps surae were performed after nerve block (4 weeks, 8 weeks, 16 weeks). The ratios of each values of right limb to those of left limb were used to evaluate the nerve block effect. RESULTS: The ratios of CMAP amplitude, tension, and slope of 3% group were 0.36, 0.55, and 0.56 at 4 weeks and those of 5% group were 0.21, 0.25, and 0.58. There were statistically significant differences of the CMAP amplitude and tension ratios, however there was no statistically significant difference of the slope ratio between two groups at 4 weeks. The ratios of CMAP amplitude, tension, and slope of 5% phenol group were increased with time. CONCLUSION: Nerve block effects by 5% phenol solution were greater than 3%. These data suggest that nerve block effect can be titrated with concentration of phenol solution.

Comparison of Amplitude to Area of Compound Muscle Action Potentials after Peripheral Nerve Injury

The evaluation of peripheral nerve disorders has traditionally relied on clinical history, physical examination, and electrodiagnostic studies. The electrodiagnostic study is currently most popular procedure. The purpose of this study is to assess the significance of the changes of amplitude and area of compound muscle action potentials(CMAPs) in peripheral nerve injury. After compression of sciatic nerve in 65 Korean house rabbits, the amplitude and the area of CMAPs were compared to each other before and after compression injury. The correlation coefficients between the changes of the parameters, amplitude and area, were obtained at a scheduled interval, and the parameters were also assessed when the evidence of denervation and regeneration was seen. In addition, the relationship between the degree of abonormal spontaneous activities and each parameter was assessed. At preinjury state, there was a significantly high correlationship between two parameters. The correlation coefficients were 0.764 and 0.756 with distal and proximal stimulations respectively in abductor hallucis recordings, and 0.649 in gastrocnemius recording. At postinjury, there was more significant high correlationship between two parameters. The correlation coefficients were 0.955 and 0.962 with distal and proximal stimulations respectively in abductor hallucis recordings, and 0.930 in gastrocnemius recording. Nineteen cases showed denervation activities at postinjury 4th day. Of those cases, the amplitude was decreased earlier in 2 cases and the area in 3 cases at the same day. Of 10 cases regenerated, the amplitude was normalized earlier than the area in 2 cases. There was a significant decrement tendency in both amplitude and area with the degree of abnormal spontaneous activities. Therefore, both the amplitude and the area of CMAPs are good quantitative indices of peripheral neuropathy and useful parameters in long-term follow up study.