Viewpoint Of Molecular Biology Research Articles

Human Resource Development in Pharmaceutical Sciences in the New Era of Life Science

Almost 20 years have passed since the six-year pharmaceutical education started as the standard educational course for pharmacists. The six-year pharmaceutical education was originally proposed to nurture the pharmacists who can play important roles in advanced medical care as part of the medical team. Importantly, recent advances in life science are providing additional scientific advantages for the graduates from the six-year pharmaceutical education system. In the new era of life science, clinical training in the six-year education will be beneficial not only for the clinical pharmacists but also for the pharmaceutical scientists. For example, in drug discovery research, numerous studies have been making efforts to identify therapeutic targets based on basic sciences so far. However, as a result of the innovation in life science, such as multi-omics analyses and molecular imaging, we can now perform patient-/disease-oriented research on molecular basis using clinical materials and information. Nowadays, with the help of data science, we can understand the pathophysiological status of individual patients and optimize pharmacotherapy from viewpoint of molecular biology in clinical setting. Moreover, in drug discovery research, we can explore and identify the drug targets by analyzing clinical samples and medical records. Thus, learning from the bedside in detail will develop future leaders, including pharmacists, scientists and pharmacist-scientists, who will pave the way for pharmaceutical sciences in the next generation.

Associations of Interleukin-1β with H. pylori-Induced Gastric Atrophy and Syndrome of Dampness-Heat in the Spleen and Stomach in Subjects with H. pylori-Related Gastric Diseases.

H. pylori-related gastric diseases (HPGD) are a series of gastric mucosal benign and malignant lesions associated with H. pylori infection. Exploring the pathogenesis of HPGD will be of great significance to prevent and treat gastric malignancy. Traditional Chinese medicine (TCM) syndrome is the essence of TCM, reflecting the state of whole body. Potential similarities of TCM syndrome may provide a new perspective in understanding development and treatment of diseases. To seek an early warning signal for gastric malignant pathology and similarities of TCM syndrome from the viewpoint of molecular biology, we examined the relationships among H. pylori, gastric pathology, and TCM syndrome and effects of Interleukin-1β (IL-1β) gene polymorphisms and expression on gastric pathology and TCM syndrome in HPGD. The results indicated that detection of H. pylori with differentiation of TCM syndrome may have a predictive function to gastric pathology. H. pylori may lead to gastric atrophy via enhancing IL-1β mRNA expression, and IL-1β mRNA overexpression in gastric mucosa may be one of the generality characteristics for H. pylori-negative subjects with syndrome of dampness-heat in the spleen and stomach.

An Evaluation on Oral Vestibular Schwannoma Growth from the View Point of Molecular Biology

An Evaluation on Oral Vestibular Schwannoma Growth from the View Point of Molecular Biology

Science and Hypothesis: An Evaluation on Oral Vestibular Schwannoma Growth from the Viewpoint of Molecular Biology

Science and Hypothesis: An Evaluation on Oral Vestibular Schwannoma Growth from the Viewpoint of Molecular Biology

Placental Development and Nutritional Environment.

The placenta is considered to have developed recently in mammalian evolution. While the fundamental function of the placenta, i.e., providing nutrients and oxygen to the fetus and receiving waste products, is the same in all mammals, the morphology of the placenta varies substantially in a species-dependent manner. Therefore, considerable interest exists in understanding placental development and function in mammals from a molecular biological viewpoint. Numerous recent studies have shown that various environmental factors before and during pregnancy, including nutrition, affect placental formation and function and that alterations in placental formation and function can influence the developing fetus and the offspring after birth. To date, the relationship between nutrition and the placenta has been investigated in several species, various model organisms, and humans. In this chapter, we discuss the current knowledge of the placenta and the epigenome and then highlight the effects of nutrition during pregnancy on the placenta and the fetus and on the offspring after birth.

Genetic Association between Amyotrophic Lateral Sclerosis and Cancer.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. An ALS drug, Riluzole, has been shown to induce two different anticancer effects on hepatocellular carcinoma (HCC). In light of this finding, we explore the relationship between ALS and cancer, especially for HCC, from the molecular biological viewpoint. We establish biomarkers that can discriminate between ALS patients and healthy controls. A principal component analysis (PCA) based unsupervised feature extraction (FE) is used to find gene biomarkers of ALS based on microarray gene expression data. Based on this method, 101 probes were selected as biomarkers for ALS with 95% high accuracy to discriminate between ALS patients and controls. Most of the genes corresponding to these probes are shown to be related to various cancers. These findings might provide a new insight for developing new therapeutic options or drugs for both ALS and cancer.

Search for useful biomarkers in hepatocellular carcinoma, tumor factors and background liver factors(Review).

Hepatocarcinogenesis is a complex and multistep process that involves the accumulation of genetic and epigenetic alterations in regulatory genes. To understand the development of hepatocellular carcinoma (HCC), current research has utilized improved array technologies. The identification of cancer-related molecules could lead to the development of novel molecular targets for treatment and biomarkers for predicting prognosis. However, prognostic prediction is insufficient when considering only tumor factors, since hepatocarcinogenesis is also greatly influenced by the status of the background liver. Clinical background liver factors, such as the presence of chronic active hepatitis or cirrhosis, are well known as risk factors for developing HCC. In contrast, genetic or epigenetic background liver factors remain unknown, albeit those are important to understand the developing process of HCC. Investigating background liver factors could contribute to the development of carcinogenic markers of HCC and to the prevention of the development of HCC. In the present study, we review the currently identified tumor factors and background liver factors from a molecular biological viewpoint and also introduce our combination array analysis.

Evaluation of laparoscopic resection of colorectal carcinoma from the viewpoint of molecular biology.

AimDetection of the possible impact of surgical management on the occurrence of minimal residual disease (MRD) in patients with colorectal carcinoma (CRC) in bone marrow samples, portal and peripheral blood samples. Comparison of MRD prevalence in patients with laparoscopic resection of CRC and those with open colorectal resection. Assessment of the potential impact of MRD on the relapse of the disease and overall survival of patients.Material and methodsThe study included 124 patients with primary CRC without proven distant metastases indicated for elective laparoscopic resection and operated on between September 21, 2006 and December 31, 2008 at the Department of Surgery, Hospital and J.G. Mendel Oncological Centre Novy Jicin. 6 samples were collected from each patient to determine MRD (system venous blood and bone marrow at the beginning of surgery, venous blood from mesenteric bloodstream, system venous blood after the resection, system venous blood and bone marrow 1 month after the surgery). Detection of MRD on the basis of CEA expression was performed by real-time RT-PCR technique. The results were compared with those obtained within the similar research using the same methodology at the 2nd Department of Surgery, University Hospital in Olomouc (the group included 230 patients treated with open resection of CRC).ResultsIn the group of patients treated with laparoscopic resection, a correlation between positive MRD in the sample of bone marrow collected before the surgery and the stage of the disease was found (p < 0.035). We also recorded the impact of surgical management on MRD occurrence in system venous blood in primary negative patients (p < 0.025). However, in the course of the short period of time we have not found a statistically significant correlation between the finding in patients with stage I-III, and the period prior to the relapse of the disease (p < 0.59). With regard to the results obtained, we can expect a potential direct correlation between a positive MRD finding in system venous blood taken prior to surgery in patients with stage I-III CRC and shorter time of survival (p < 0.075). In the group of patients treated with open resection of CRC, no statistically significant relationship between the stage of the disease and MRD occurrence was found. Incidence of circulating tumour cells (CTC) in the samples of venous blood taken prior to surgery is a prognostically important factor (p < 0.05) from the viewpoint of disease-free survival (DFS). Another prognostically important factor with regard to DFS seems to be the occurrence of disseminated tumour cells (DTC) in the bone marrow taken 1 month after the surgery.ConclusionsThe data recorded suggest a relationship between MRD finding and the disease prognosis. Collection of samples as well as evaluation of results continue as we strive to include more patients in our study and to obtain more data within 5-10 years of the follow-up. The comparison between the data obtained in the laparoscopic approach and the data obtained in open resection performed from the viewpoint of molecular biology did not show a significant difference in MRD detection in the samples collected after the surgery.

A new analogical analysis for two concepts of Iranian traditional medicine (TIM) from the viewpoint of molecular biology

A new analogical analysis for two concepts of Iranian traditional medicine (TIM) from the viewpoint of molecular biology

A bio-inspired structural health monitoring system based on ambient vibration

A structural health monitoring (SHM) system based on naïve Bayesian (NB) damageclassification and DNA-like expression data was developed in this research. Adapted fromthe deoxyribonucleic acid (DNA) array concept in molecular biology, the proposedstructural health monitoring system is constructed utilizing a double-tier regressionprocess to extract the expression array from the structural time history recordedduring external excitations. The extracted array is symbolized as the variousgenes of the structure from the viewpoint of molecular biology and reflects thepossible damage conditions prevalent in the structure. A scaled down, six-story steelbuilding mounted on the shaking table of the National Center for Research onEarthquake Engineering (NCREE) was used as the benchmark. The structuralresponse at different damage levels and locations under ambient vibration wascollected to support the database for the proposed SHM system. To improve theprecision of detection in practical applications, the system was enhanced by anoptimization process using the likelihood selection method. The obtained arrayrepresenting the DNA array of the health condition of the structure was first evaluatedand ranked. A total of 12 groups of expression arrays were regenerated from acombination of four damage conditions. To keep the length of the array unchanged,the best 16 coefficients from every expression array were selected to form theoptimized SHM system. Test results from the ambient vibrations showed thatthe detection accuracy of the structural damage could be greatly enhanced bythe optimized expression array, when compared to the original system. Practicalverification also demonstrated that a rapid and reliable result could be givenby the final system within 1 min. The proposed system implements the idea oftransplanting the DNA array concept from molecular biology into the field of SHM.

From a Molecular Biological Viewpoint, Does Endothelin Type A Receptor Antagonist Therapy Reduce Diabetes-induced Testicular Damage in Rats?

To evaluate the therapeutic effects of a selective endothelin type A receptor antagonist (ERA-A) on testis of streptozotocin (STZ)-induced diabetic rats. Eighty rats were analyzed in 4 groups: healthy controls, diabetic rats, diabetic rats treated with ERA-A, and healthy rats treated with ERA-A. Diabetes was induced in 40 rats by a single intraperitoneal injection of STZ and followed for 2 months. A total of 20 diabetic and 20 healthy rats were also intravenously treated with ERA-A at days 7 and 15. The remaining untreated healthy rats served as controls. Blood glucose levels of ≥ 250 mg/dL were considered to indicate diabetes and were measured at the end of the second month. Formalin-fixed paraffin-embedded testis tissue sections were analyzed after staining with hematoxylin and eosin or specific antibodies for apoptotic markers. mRNA expressions of genes involved in the apoptotic pathway or spermatogenesis were evaluated by real-time reverse transcription-polymerase chain reaction. Major therapeutic effects of ERA-A could be achieved for damages caused by oxidative stress. Although a decrease in apoptotic cell death could be detected, no statistically meaningful results could be obtained for the duration of spermatogenesis. ERA-A could prevent germ cell death by apoptosis and testicular damage in diabetic rats.

Chronobiology of acute myocardial infarction molecular biology

The incidence of heart attacks increases in the early morning. This circadian oscillation is closely related to the function of the internal biological clock. In this article, we review the chronobiology of acute myocardial infarction (AMI) from the viewpoint of molecular biology.

Genotype Analysis of Measles Viruses, 2002

In 2002, through the communicable disease reporting system, 77 suspected cases of measles had been reported. Of them, 27, were confirmed by serological testing. By conventional epidemiological investigation, they could be grouped in five chains and 13 sporadic cases. The Taichung area had the largest number of 15 confirmed cases. This was second to the 31 confirmed cases identified in 1994. The first confirmed case in 2002 occurred in February. In July and August, cases were reported one by one in the Taichung area; and in mid-September ill early October, cases were still reported from three junior high and primary schools in Taichung County. The outbreak was controlled in late-October after the checking of immunization records and make-up vaccination by the Disease Control Division of the Center for Disease Control. In the outbreaks in schools, wild-type measles viruses were isolated in specimens of three patients. By nucleoprotein gene sequencing, they were found to be the H1 genotype. Conventional epidemiological surveys of contact history could not always disclose associations between cases. In addition to the isolated virus strains, RNAs were extracted from clinical specimens such as sera, throat swabs or urine for PT-PCR. The products so obtained were sequenced, and compared for their nucleoprotein genes to investigate the epidemic from the viewpoint of molecular biology.

Physiology of vertebrates under micro-gravity with special reference to the Ca metabolism

On April 12, 1961, Major Yurii A. Gagarin of the former-U.S.S.R. Air Force circled the Earth in a spacecraft named "Vostok", a word which means "east". He spent 1 hour and 48 minutes in space. Since then, the U.S.S.R. and the U.S.A. have sent many astronauts into space. In one case, the stay in space exceeded a year in length, reaching 438 days. Through these experiences, it became clear that micro-gravity caused various problems in human physiology. One of the most serious problems was the loss of Ca from bones, as a result of the negative expenditure of Ca. Under 1G on the ground, bone absorption and bone formation proceed in accordance. Under micro-gravity, however, this balance is broken. Although this phenomenon has been widely analyzed from the viewpoint of molecular biology as well, studies to clarify the mechanism that causes the disorder of Ca metabolism in bones have just started. At present, no perfect treatment to prevent the loss of Ca from bones is available.

A mild form of pseudoachondroplasia: minimal epi-metaphyseal involvement of long bones

A problem in diagnosing pseudoachondroplasia (PSACH) is that the pathognomonic changes of vertebral bodies invariably disappear around the age of 10, and an adult case might subsequently be misdiagnosed as MED, Fairbank type, though the latter is less severe than PSACH. We present a Japanese girl (follow-up, 3–10 years of age) whose epi-metaphyseal involvement of long bones was minimal and whose height was +2 S.D. of standard for PSACH in spite of the typical changes of the vertebral bodies. She might not have been diagnosed only as PSACH but also as MED, Fairbank type, after disappearance of the typical vertebral body changes because of the apparent lack of stubby fingers. Since the overlap of PSACH and MED has recently been discussed from the viewpoint of molecular biology, study of the spectrum of clinical features of PSACH is important.

On the dependence of life evolution on geotectonic stages

The Brno biologist S. Rosypal (1994 a, b) summarized the state-of-the-art concerning the origin of life from a molecular-biological viewpoint. From among the literature quoted by Rosypal, the author wishes to mention, at least, Beaudry, Joyce 1992 and Joyce 1989. In addition, Rosypal called the author's attention to the paper by Darnell, Lodish, Baltimore 1990. The viewpoint presented by Rosypal caused the author to consider the question whether the interpretation of the impacts of the periods of a galactic year could be extended to terrestrial life. Some time ago the author (Květ 1992) published his conception of the dependence of animal evolution on geotectonic stages for the past 1.3 thousand million years. It has been found that, at present, deciding impacts from the universe can be observed for both the geologic history of the Earth and the whole evolution of terrestrial life. As far as the planet Earth is concerned, the author demonstrated in his paper dealing with a periodical geological time table (Květ 1991a, b) how the duration of a geotectonic stage can depend on the galactic year that lasts 220 million years (revolution of the Solar System round the centre of the Milky Way our Galaxy). What is also showing up is the hierarchy in the "significance" of the individual tectonic stages. Geotectonic stages of different hierarchical order alternate in accordance with the 2n model (Fig 1, 2). The hierarchical order of a geotectonic stage determines the intensity of recurring geological events that manifest themselves in the Earth's crust and also affect the evolution of life. The model mentioned allowed to include a pre-geologic tectonic stage in the geological time table. This stage the most significant one, of first order corresponds to the period of the accretion induced origin of the Earth (accumulation of cosmic material) during the time interval from 4.87 thousand million to 4.65 thousand million years before the present. It could also be demonstrated that any two following each other geotectonic stages constitute a regularly appearing couple, in which the second stage is of fifth order and the first of some superior order (Tab 1). It should be pointed out that the generation of the protocontinental crust in the fifth, Pre-Saamian, geo-tectonic stage turned out to be the most significant of all of the geological events. Next to the pregeologic stage, the Pre-Saamian stage, being of third order, is of crucial importance to the primary development of the Earth till the ninth, Wanipigowan, stage that is of second order (Fig 2). The author concluded (Květ 1990a) that, among others, geometrical networks of rupture systems were formed and the so-called global glaciation of the Earth came about in the final phases of the individual geotectonic stages. As assumed by the author, these events could result from the passage of the Solar System through a section of the Milky

The complete amino acid sequence of the Clostridium botulinum type D neurotoxin, deduced by nucleotide sequence analysis of the encoding phage d-16 phi genome.

The complete nucleotide sequence of Clostridium botulinum type D strain CB16 neurotoxin was determined and the deduced amino acid sequence is reported here for the first time. The structure and function of botulinum type D neurotoxin is discussed from a molecular biological viewpoint. DNA was extracted from toxin-converting phage d-16 phi of C. botulinum type D strain CB16, and a fragment (about 10 kbp) coding for the neurotoxin was cloned into Escherichia coli using lambda gt11. A 21-mer oligonucleotide which corresponds to Phe7 to Val13 of the partial amino acid sequence near the N-terminus of the type D neurotoxin was synthesized and used as a probe to identify the gene encoding type D neurotoxin. The nucleotide sequence contained a single open reading frame coding for 1,275 amino acids (molecular weight of 146,785) and the deduced amino acid sequence corresponded exactly to the partial amino acid sequences determined by direct microsequencing of the neurotoxin fragments. In the dichain molecule of the neurotoxin, Thr2 and Asn443 formed the N-termini of the light chain (M.W. 50,410) and heavy chain (M.W. 96,394) respectively, and these two chains were linked with a disulfide bond between Cys437 on the light chain and Cys450 on the heavy chain. The nucleotide sequence of the D-CB16 neurotoxin differed from that previously reported for type D neurotoxin by three nucleotides.

Effective mechanisms of hormones from the viewpoint of molecular biology

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study