Dual-targeting compounds possessing enhanced anticancer activity via microtubule disruption and histone deacetylase inhibition.

Dual-targeting anticancer agents 4-29 are designed by combining the structural features of purine-type microtubule-disrupting compounds and HDAC inhibitors. A library of the conjugate compounds connected by appropriate linkers was synthesized and found to possess HDACs inhibitory activity and render microtubule fragmentation by activating katanin, a microtubule-severing protein. Among various zinc-binding groups, hydroxamic acid shows the highest inhibitory activity of Class I HDACs, which was also reconfirmed by three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore prediction. The purine-hydroxamate conjugates exhibit enhanced cytotoxicity against MDA-MB231 breast cancer cells, H1975 lung cancer cells, and various clinical isolated non-small-cell lung cancer cells with different epidermal growth factor receptor (EGFR) status. Pyridyl substituents could be used to replace the C2 and N9 phenyl moieties in the purine-type scaffold, which can help to improve the solubility under physiological conditions, thus increasing cytotoxicity. In mice treated with the purine-hydroxamate conjugates, the tumor growth rate was significantly reduced without causing toxic effects. Our study demonstrates the potential of the dual-targeting purine-hydroxamate compounds for cancer monotherapy.

Assessment of antibiotic resistance patterns in Central Taiwan during the COVID-19 pandemic: A retrospective study.

BACKGROUND: Antimicrobial resistance (AMR) is a growing worldwide public health issue due to the overuse and inappropriate use of antibiotics. AMR has been more prevalent during the coronavirus pandemic of 2019 (COVID-19) compared to previous periods. Therefore, this study was conducted to evaluate the AMR profile of common bacteria that were isolated for routine analysis during the pandemic of COVID-19 in Central Taiwan. The main goal of this study was to examine and analyze the AMR patterns both before and after the start of the COVID-19 pandemic. METHODS: We conducted a retrospective analysis of clinical samples collected from two different time periods: the 1-year period before the onset of the COVID-19 pandemic (January 2019 to December 2019) and the 2-year period following the start of the pandemic (September 2020 to September 2022). The data for this study were obtained from clinical records, and both bacterial identification and antibiotic susceptibility testing were performed using the Phoenix identification system. RESULTS: Among the 8152 bacterial isolates obtained during the study period from September 2020 to September 2022, 4022 (49.3%) were Escherichia coli, 1346 (16.5%) were Klebsiella pneumoniae, 1156 (14.2%) were Staphylococcus aureus, 887 (10.9%) were Pseudomonas aeruginosa, 376 (4.6%) were Enterococcus faecium, and 365 (4.5%) were Acinetobacter baumannii. The overall prevalence of resistant bacteria during the COVID-19 pandemic was as follows: vancomycin-resistant Enterococcus, 69%; carbapenem-resistant A. baumannii, 65%; methicillin-resistant S. aureus, 49%; carbapenem-resistant K. pneumoniae, 29%; carbapenem-resistant P. aeruginosa, 17%; and carbapenem-resistant E. coli, 2%. Carbapenem-resistant A. baumannii, vancomycin-resistant Enterococcus, carbapenem-resistant K. pneumoniae, and carbapenem-resistant E. coli increased by 19%, 10%, 2%, and 1%, respectively. On the other hand, carbapenem-resistant P. aeruginosa and methicillin-resistant S. aureus decreased by 6%, respectively. CONCLUSION: This study provides a comprehensive assessment of AMR during the COVID-19 pandemic in Central Taiwan. Understanding the prevalence of AMR is crucial for preventing infection and formulating disease prevention policies. Further research is warranted to elucidate the correlation between AMR and the severity of infection in COVID-19 patients.

Retrospective Analysis of Allergen Distribution Dynamics in Central Taiwan.

Introduction: Allergy is a type Ⅰ hypersensitivity reaction to certain substances (allergens) such as environmental factors, food and drugs. Allergies are a significant public health issue, and therefore, understanding the distribution patterns of allergens in specific regions is important. This study aimed to retrospectively analyse allergen distribution patterns in Central Taiwan over a 5 years period (2018-2022). Methods: Data of patients who had allergen sensitization testing using the OPTIGEN® Allergen-Specific IgE Assay from the 1st of January 2018 to the 31st of December 2022 were reviewed retrospectively. Statistical analyses were performed to determine the prevalence and distribution of allergens in our study population. Results: A total of 8,444 patients (3,784 males and 4,660 females) who attended the Asia University Hospital for allergen detection were enrolled in this study. Dermatophagoides farina (41.8%), Dermatophagoides pteronyssinus (37.9%), house dust (24.6%), cockroach mix (17.7%), crab (12.6%), clam (9.8%), shrimp (9.1%), cat dander (8.1%), pig weed (8%) and peanut (7.8%) were identified as the ten allergens that most commonly induced sensitization in our study population. Additionally, crab, clam, shrimp, peanut and beef were the five most common food allergens. Conclusion: In summary, our findings contribute significantly to the knowledge on allergen distribution in Central Taiwan. Our identification of prevalent allergens may contribute to an improved understanding of the epidemiology of allergies in this region.

Optimizing Blood Culture Volumes by Implementing PDCA Cycle Management.

BACKGROUND: The aim of this study was to optimize the mean volume of blood drawn by nurses to a level that is recommended by our hospital through the implementation of PDCA cycle management. The purpose of the current study was to match the mean volumes of blood drawn with the volume recommended by the manufacturer. METHODS: The adequacy of blood volume in a bottle of aerobic blood culture per venipuncture was evaluated for every month from January 2021 to March 2022 by using the Becton Dickinson BD blood volume monitoring system. Furthermore, the study compared changes in the mean blood volumes before and after the PDCA cycle management was implemented. RESULTS: The mean blood volumes calculated for Q1 2021 (January 2021 to March 2021) before the PDCA cycle management was 6.3 mL per culture bottle. After PDCA cycle management was implemented, the mean blood volumes for Q1 2022 (January 2022 to March 2022) were calculated as 8.6 mL (p < 0.01). In addition, the positive culture rate increased from 13% to 15%. CONCLUSIONS: Implementing the PDCA cycle management can improve the mean blood culture volumes effectively and match the volume recommended by the manufacturer. Additionally, our study indicated that a higher blood volume yielded a culture rate that was significantly positive.

Evaluation of Friedewald's Formula for Plasma LDL-Cholesterol Estimation.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) can contribute to atherosclerosis if it is oxidized within the walls of arteries. Therefore, LDL-C plays an important role in cardiovascular disease risk assessment and prevention. The current study aims to evaluate the validity of Friedewald's formula in the Taiwanese population. METHODS: In this analytical cross-sectional study, a data set containing 31,729 results was used and lipid profiles of all samples were measured using the Beckman Coulter AU680 clinical chemistry analyzer. This study was conducted from September 2016 to August 2019. RESULTS: The agreement between the direct and calculated LDL-C was significant with Pearson's correlation coefficient (r) of 0.904 (p < 0.001). Mean LDL-C levels were 99.3 ± 32.8 mg/dL and 95.3 ± 37.6 mg/dL for direct and calculated LDC-C, respectively. CONCLUSIONS: Good agreement was observed between direct and calculated LDC-C. Therefore, it can be concluded that Friedewald's formula is applicable in LDL-C estimation when the direct method is not affordable.

Interference of Blood Glucose Testing by an Increase in Serum IgM Levels.

BACKGROUND: An absurd result of plasma glucose test caused by increased serum IgM levels. METHODS: Serum immunoglobulin levels are determined by using an immunoturbidimetric assay. Additionally, serial dilutions were performed to assess the absurd results. RESULTS: Our results showed that an increase in serum IgM levels induces errors in the measurement of the plasma glucose level. CONCLUSIONS: This study simply presents a message that both medical technologists and physicians need to be aware of this because improper results of blood glucose levels may result in aggressive and invasive patient management. Additionally, physicians may be led to wrong interpretation due to false levels of glucose. In fact, we do not know how often this situation accidentally occurs in the laboratory. Therefore, all medical technologists must stay alert to absurd and unusual test results and reconfirm the reason for an absurd result.

Complete mitogenome of Antheraea formosana Sonan, 1937 (Lepidoptera: Saturniidae): an endemic silkmoth in Taiwan.

The complete mitogenome of an endemic silkmoth in Taiwan, Antheraea formosana, was determined using Illumina next-generation sequencing. The mitogenome is 15,318 bp in length and consists of 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs, and one non-coding control region. The overall base composition of the mitogenome showed a high A + T bias, and the A + T content (80.2%) was significantly higher than the G + C content (19.8%). All PCGs use the typical ATN as the initiation codon, with the exception of cox2, which begins with GTG, respectively. The complete mitogenome was used to reconstruct a phylogenetic tree, indicating that A. formosana is more closely related to Antheraea assamensis than other Antheraea species, with 93.19% nucleotide similarity.

Complete mitochondrial genome of Manispentadactylapentadactyla (Mammalia: Pholidota), an endemic subspecies of Chinese pangolin: mitogenome characterisation and phylogenetic implications.

The Chinese pangolin Manispentadactyla is critically endangered because of over-exploitation and illegal trafficking and includes three subspecies. However, the taxonomic status of the three subspecies of the Chinese pangolin has not been well resolved, which impedes regional conservation and illegal trade traces. In this study, the complete mitogenome sequence of M.p.pentadactyla, an endemic subspecies of the Chinese pangolin in Taiwan, was determined. The complete mitogenome of M.p.pentadactyla is 16,570 base pairs (bp) in length with 13 protein-coding genes (PCG), 23 transfer RNAs (tRNAs), two ribosomal RNAs and a 1164 bp control region. The overall base composition of the genome showed a slight A + T bias (59.9%), positive AT skew (0.1515) and negative GC skew (-0.3406), which is similar to that of other pangolins. All PCGs started with a typical ATN codon and all tRNAs were typical cloverleaf-shaped secondary structures, except for tRNA-Ser(GCU). Phylogenetic analysis indicated a monophyletic relationship for M.p.pentadactyla and M.p.aurita and was monophyletic for M.p.pentadactyla, but paraphyletic for M.p.aurita. The paraphyly of M.p.aurita resulted from an incomplete lineage sorting. This study enriched the mitogenome database of the Chinese pangolin and the molecular information obtained should be very useful for future research on mitogenome evolution and genetic diversification in M.pentadactyla.

Structure-guided development of purine amide, hydroxamate, and amidoxime for the inhibition of non-small cell lung cancer.

An 8-oxopurine-6-carboxamide compound (1a) was previously identified as an inhibitor of non-small cell lung cancer (NSCLC). In this study, more than 30 purine-6-carboxamide derivatives with variations at the C2, N7, C8, and N9 positions were synthesized to investigate the structure-activity relationship as a basis for the construction of an advanced pharmacophore model. This model suggests that purine-6-hydroxamate and purine-6-amidoxime analogs could form more hydrogen bonds with a target protein to enhance the inhibitory activities against H1975 cells. Among the series of analogs, hydroxamate 17 and amidoxime 19a exhibited excellent potency against H1975 cells (IC50 < 1.5 µM) and other lung cancer cells with either wild-type or mutated epidermal growth factor receptor (EGFR). Mouse experiments indicated that compounds 17 and 19a were efficient anticancer agents with no appreciable toxicity. The mechanisms of action for the induction of cell apoptosis were determined to involve microtubule fragmentation and p53-mediated signaling pathways.

Antifatigue properties of tanshinone IIA in mice subjected to the forced swimming test.

CONTEXT: Tanshinone IIA (Tan IIA) is a constituent of Danshen Salvia miltiorrhiza Bunge (Lamiaceae); however, its antifatigue activity remains unclear. OBJECTIVE: To study the antifatigue properties of Tan IIA and its underlying mechanisms. MATERIALS AND METHODS: In program I, three mouse groups were separately subjected to three gavages with 0, 1 and 6 mg/kg Tan IIA and forced swimming test (FST) weekly for 8 weeks; in program II, one gavage with 0, 2 and 10 mg/kg Tan IIA was administered plus FST weekly for 4 weeks. Serum glucose, lactate, superoxide dismutase (SOD), malondialdehyde (MDA) and blood urea nitrogen (BUN) were determined after final FST. RESULTS: Tan IIA significantly prolonged swimming durations in program I but not in program II. Swimming times were 3208 ± 1054 and 2443 ± 1054 s for the 1 and 6 mg/kg treatments and 856 ± 292 s for the vehicle control. The two doses significantly reduced serum glucose levels (40.3 ± 8.5 and 60.0 1 ± 11.8 mg/kg) and lactate levels (61.3 ± 27.5 and 68.8 ± 8.5 mg/kg) in treated mice compared with those in control mice (137.5 ± 38.6 mg/kg and 122.7 ± 18.2 mg/kg, respectively). However, no significant differences were observed regarding SOD, MDA or BUN levels. DISCUSSION AND CONCLUSIONS: Tan IIA has antifatigue activity and is associated with reductions in serum glucose and lactate levels. Further studies should assess muscle hypertrophy and efficient aerobic glycolysis caused by Tan IIA. Tan IIA has potential as a pharmacological agent for fatigue resistance.