Mechanochemical synthesis of novel metronidazole cocrystal: Structure characterization and pharmaceutical properties study.

A new cocrystalline form of metronidazole (MET) with propyl gallate (PRO), referred to as MET-PRO, has been successfully synthesized and characterized. Structural characterization reveals that MET and PRO are present in a 1:1 ratio within the cocrystal lattice, with one water molecule equivalent incorporated into the structure. This arrangement facilitates the formation of MET-PRO heterodimers and multiple stable units, collectively constructing a three-dimensional supramolecular network. The solubility and permeability of the current cocrystal, along with the parent drug MET, are evaluated under physiological pH conditions. Experimental findings reveal that MET within the cocrystal exhibits a 1.54-2.37 folds increase in solubility and approximately a threefold improvement in permeability compared to its standalone form. Intriguingly, these concurrent enhancements in the physicochemical properties of MET lead to augmented antibacterial activity in vitro, evidenced by a reduction in minimum inhibitory concentration. Even more intriguingly, the enhanced physicochemical properties observed in vitro for the current cocrystal translate into tangible pharmacokinetic benefits in vivo, characterized by prolonged half-life and enhanced bioavailability. Consequently, this research not only introduces a fresh crystal structure for antibacterial medication but also presents approach for optimizing drug properties across in vitro and in vivo settings, while concurrently bolstering the antibacterial effectiveness of MET through pharmaceutical cocrystallization techniques.

A dual molecular beacon approach for fast detection of Mycobacterium tuberculosis.

The main objectives of this study were to assess a dual molecular beacon approach for fast detection of Mycobacterium tuberculosis (MT). MT beacon (Tb-B) was designed to target the unique IS6110 (114 bp) and rpoB (215 bp) fragment of the MT (H37Ra) genome, and the two fragments were inserted into the PMD-19T vector after purification, by PCR and sequencing, to construct plasmids. Different dilutions of positive plasmid standards were used for dual molecular beacon RT-PCR of rpoB and IS6110, and standard curves were established.The results show that the dual molecular beacon of rpoB and IS6110 detecting MT was stable (CV is 1.91-2.68 %) with a high amplification efficiency (95.6 %). In addition, the strains of non MT did not generate fluorescence signals, while strains of MT did, indicating that the primers and molecular beacons were specific, and only MT complex was amplified. The linear range was wide (10(3)-10(11) copies/mL), and clinical specimens presenting different bacterial counts can be detected.

[Evaluations of urinary sediment and dry chemical detection in urinary tract infections].

OBJECTIVE: To assess the diagnostic values of urinalysis in urinary tract infections. METHODS: A total of 526 urine culture specimens were analyzed by UF-1000i urine analyzers and GEB600 urine chemistry analyzer to determine the sensitivity and specificity of individual and combined analysis of white blood cell, bacteria count and nitrite test in the diagnosis of urinary tract infections. And bacterial culture was used as the gold standard. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of bacterial count were the highest in individual analysis at 84.3%, 90.5%, 84.3%, 90.5% and 88.2% respectively. The sensitivity, specificity, positive predictive value and accuracy of combined bacterial count and leukocyte was 83.9%, 91.0%, 85.4% and 88.2% respectively while the negative predictive value of white blood cell and nitrite was highest (91.3%). Compared with the combined or single analysis, the combination of three analyses had the highest sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate at 85.4%, 92.6%, 84.7%, 93.0%, 90.3% respectively. CONCLUSION: The combined urinalysis may be used as a rapid screening indicator of urinary tract infections.

[Epidemiological studies on close contacts of smear-positive tuberculosis patients in Shijiazhuang city from 2007 to 2008].

OBJECTIVE: To analyze the incidence of tuberculosis (TB) in people who were in close contact with smear-positive TB patients. METHODS: A total of 19 159 subjects, including 17 334 family members and 1825 classmates of patients, in close contact with 6653 smear-positive TB patients in Shijiazhuang city from 2007 to 2008 were observed. All the classmates were tested by purified protein derivative (PPD) test and symptom screening, and all family members were screened by symptoms. All these subjects were trained with knowledge related to TB. The ones with positive PPD test and suspected TB symptoms were further examined by chest X-ray and sputum smear microscopy, and those without any symptom were followed up monthly throughout a two year period and were examined at any time if symptoms occurred. RESULTS: A total of 281 patients with pulmonary TB were diagnosed in 2 years, including 176 family members and 105 classmates in all close contacts. The smear-positive incidences were 1466.67/100 000. The incidences for 14 - 25 years old group and more than 75 years old group were 2907.18/100 000 (83/2855) and 2650.96/100 000 (18/679), which were higher than those for other groups. Two higher incidences were related to close contact time periods of 6 months (929.07/100 000, 178/19 159) and 13 - 18 months (369.12/100 000, 70/18 964). Three highest incidences were observed in the roommates (11 384.62/100 000, 37/325), classmates (4533.33/100 000, 68/1500) and couples (1624.17/100 000, 86/5295). CONCLUSION: Closer contact with smear-positive patients with TB may result in the higher chance of TB. Close contact for 6 months or 13 to 18 months caused more patients, and the 14 - 25 years old group and more than 75 years old group had higher incidences of TB.

AKR1C1-3, notably AKR1C3, are distinct biomarkers for liver cancer diagnosis and prognosis: Database mining in malignancies.

Aldo-keto reductases, known as AKR1C1-AKR1C4 enzymes, are pivotal to NADPH-dependent reduction, and their expression is highly associated with the progression of malignant cancers. However, the expression and distinct prognostic value of the AKR1C family members in liver cancer are not well established. In the current study, the expression of AKR1C isoforms was studied using the Oncomine online databases. In addition, their expression profiles were analyzed in cancer cell lines using data from the Cancer Cell lines Encyclopedia (CCLE) database. Furthermore, the mRNA expression levels of AKR1C family members between liver cancer and normal liver samples were assessed by the Gene Expression Profiling Interactive Analysis (GEPIA) database. The AKR1C1-3 prognostic value was further investigated by the Kaplan-Meier plotter database in liver cancer patients. It was found that the expression levels of AKR1C3 were elevated significantly in liver cancer tissues and cells as demonstrated by the Oncomine, CCLE and GEPIA databases. The expression levels of AKR1C1 and AKR1C2 in liver cancer tissues did not increase significantly in the Oncomine database while expression was significantly high in CCLE and GEPIA databases. However, the expression levels of the AKR1C4 gene as determined by the CCLE, GEPIA and Oncomine databases were not consistent. Therefore, the Kaplan-Meier survival curves of liver cancer patients with the expression of AKR1C1-3 genes were next analyzed. The data indicated that high expression levels of AKR1C1-3 were correlated with lower overall survival in liver cancer patients. Using the co-expression and PPI network, AKR1C1-3 genes were identified that were involved in the same pathway displaying 44 total unique interactors. These results suggested that the increased AKR1C1-3, notably AKR1C3 expression levels served as possible diagnostic biomarkers and essential prognostic factors for liver cancer patients. The roles of AKR1C4 in liver cancer require further examination.