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Cloning and Characterization of the Gene Encoding HMGS Synthase in Polygonatum sibiricum
The saponins of Polygonatum sibiricum had many pharmacological activities such as antitumor, antioxidation, and blood sugar lowering, which were synthesized by two pathways: mevalonate (MVA) and methylerythritol phosphate (MEP). 3-Hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) was the key enzyme in the MVA synthesis pathway, and its expression level may affect the accumulation of saponins which were the main active ingredients of P. sibiricum. In this study, we successfully cloned HMGS1 and HMGS2 from P. sibiricum and their sequence similarity was 93.71% with 89 different sites. The multiple sequence alignment results indicated that the N-terminal sequences of HMGS were conserved. Phylogenetic analysis showed that P. sibiricum, A. officinalis, N. tazetta, D. nobile, and other relatives had a common evolutionary ancestor. The expression levels of both HMGSs and the total saponin content in different tissues revealed that HMGS expression in rhizomes was positively correlated with total saponin content. Further study of the abiotic stress effect of Methyl Jasmonate (MeJA) demonstrated that the expression of HMGS1 and HMGS2 genes was induced by MeJA, peaked at 24 h, and fell by 48 h. Our present findings would provide a blueprint for future studies of HMGS and its role in triterpenoid biosynthesis in P. sibiricum.
Reliability and Validity of Korean Version of Crohn’s and Ulcerative Colitis Questionnaire-8
Background. Patients with inflammatory bowel disease (IBD) have a decreased quality of life (QoL), the improvement of which is a treatment goal. The CUCQ-8 is a verified simple and effective QoL measurement tool. We validated the Korean version of CUCQ-8 with the approval of its developer. Methods. We investigated the correlation between the Korean version of CUCQ-8 and the IBDQ-32 in patients with IBD. Results. In all, 147 subjects (male, 97 (66.0%); female, 50 (34.0%); mean age years) were analyzed. Cronbach’s alpha coefficient of the CUCQ-8 was 0.833, indicating very high internal consistency. The Korean version of the CUCQ-8 showed a significant correlation with the IBDQ-32 and its subscales (correlation coefficient, >0.75). Conclusions. The Korean version of the CUCQ-8 has high reliability and construct validity and can be used to evaluate the QoL of patients with IBD.
Resveratrol Induces Apoptosis, Suppresses Migration, and Invasion of Cervical Cancer Cells by Inhibiting the Hedgehog Signaling Pathway
To investigate the effect and mechanism of resveratrol on the biological behavior of cervical cancer cells (HeLa cells), the apoptosis, migration, and invasion of HeLa cells were detected by flow cytometry, wound healing, and transwell assays. The expression levels of Hedgehog signal pathway proteins (smoothened (SMO), zinc finger transcription factors (Gli1), and sonic hedgehog homolog (Shh)) were detected by quantitative real-time PCR (qPCR) and western blotting. Compared with that control group, resveratrol (RES) significantly induced apoptosis, inhibited the migration and invasion of the HeLa cells. The expression of SMO, Gli1, and Shh were downregulated in the HeLa cells treated with RES. The Hedgehog agonist purmorphamine (PUR) reversed the RES-induced increase of apoptosis and reduction of migration and invasion in the HeLa cells. In conclusion, RES induced the apoptosis and suppressed the migration and invasion of HeLa cells by inhibiting Hedgehog signal pathway.
Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach
In this study, we consider pyridine-N-oxide alkaloids from Allium stipitatum and their synthetic disulfide analogs (PDAs) as candidates for next-generational antimycobacterial agents, in light of growing resistance to existing conventional therapies. In silico studies involving molecular docking simulations of 12 PDAs were carried out against 7 Mycobacterium tuberculosis target proteins (MTs) to determine their theoretical binding affinities. Compounds A3, A6, and B9 demonstrated stronger binding affinities on similar MTs. Molecular descriptors (MDs) describing structural and physicochemical properties of the compounds were also calculated using ChemDes, explored using Pearson’s correlation analysis, and principal component analysis (PCA) in comparison with MDs from conventional antitubercular medicines. The PDAs possessed similar scores as isoniazid and pyrazinamide. The MDs were also used to conduct a quantitative structure-binding affinity relationship (QSBAR) study by building good fit and significant models through principal component regression (PCR) and partial least squares regression (PLSR). Leave-one-out cross-validation was adopted in the PLSR, resulting in good predictive models on all MTs (range of ; range of ). Both PCR and PLSR models predicted the significant effects of ndonr, Hy, Mol wt, nhev, nring, ndb, Log P, W, Pol, ISIZ, TIAC, Getov, and UI on the binding of ligands to the MTs. In silico prediction of PDAs’ ADMET profiles was conducted with QikProp utility. The ADMET profiles of the compounds were favorable. The outcome of the current study strengthens the significance of these compounds as promising lead candidates for the treatment of multidrug-resistant tuberculosis.
Clinical Characteristics and Risk Factors among Patients with Positive COVID-19 Test Admitted to ICU
Background. Studies that show common characteristics among ICU-admitted patients due to COVID-19 are available on the net, but such studies in Saudi Arabia are limited. Methods. A descriptive cross-sectional study establishing common comorbidities and risk factors among critically ill patients who tested positive for COVID-19 at the National Guard Hospital from March 2, 2020, to March 20, 2021. The data were obtained from the BEST Care System of King Abdulaziz Medical City, computed, and analyzed using SPSS. Results. Three hundred eighty-five COVID-19 patients admitted to the intensive care unit (ICU) were included in this study. The mean age was , 60.85% were males, and 39.2% were females. There was statistically significant positive relationship between severity of the symptoms and age (). The mean duration of hospital stay in the sample was . More than one-third (37.4%) of cases admitted to the hospital died while about two-thirds of the cases were discharged after complete recovery. Two hundred ninety (75.3%) of the patients who were admitted to the National Guard Health Affairs (Riyadh, Saudi Arabia) had respiratory disease. Two hundred twelve patients (55.1%) had diabetes mellitus, while the number of hypertensive patients was 203 (52.7%). There was a significant positive relation among patients with gastrointestinal tract infection (GIT) risk factors and the severity of the symptoms of COVID-19 (). In addition, there was a strong significant relation between hypertension patients and the severity of the COVID-19 symptoms (). Conclusion. COVID-19 patients who have GIT and hypertension have been found to be at an increased risk of COVID-19 symptom severity. Old age was also found to have an increased risk for COVID-19 symptom severity.
SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway
Castration-resistant prostate cancer (CRPC) is still challenging to treat. Dissatisfaction with androgen signal-targeted therapy forces people to look for other treatment strategies. Therefore, this study is aimed at exploring the role of SOX8/Notch signaling in CRPC. The upregulation of SOX8, Notch4, and Hes5 indicated a poor progression-free survival (PFS) in CRPC patients. The expression of these proteins was also upregulated in enzalutamide-resistant LNCaP cells (Enza-R). Moreover, knocking down SOX8 inhibited malignant biological behaviors and decreased the activation of Notch signaling in Enza-R cells. Importantly, knocking down SOX8 obviously reversed the enzalutamide resistance in Enza-R cells, while RO0429097 (a γ secretase inhibitor inactivates Notch signaling) exerted similar effects. At last, we found that both SOX8 knockdown and/or RO0429097 suppressed tumor growth and bone metastasis in vivo. Altogether, our study indicated that the SOX8/Notch signaling is involved in CRPC and that these enzymes are possible targets to develop novel treatment for CRPC.