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COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
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INTRODUCTION@#Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers.@*METHODS@#The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci.@*RESULTS@#Higher numbers of Mi foci were found in larger tumours (P = 0.031).@*CONCLUSION@#Greater extent of DCIS is associated with multifocal Mi.
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Humans , Female , Carcinoma, Intraductal, Noninfiltrating , Prognosis , Disease-Free Survival , Progression-Free Survival , Breast Neoplasms , Carcinoma, Ductal, Breast/pathology , Neoplasm InvasivenessABSTRACT
<p><b>Background</b>Excess mucus production is an important pathophysiological feature of chronic inflammatory airway diseases. Effective therapies are currently lacking. The aim of the study was to evaluate the effects of curcumin (CUR) on lipopolysaccharide (LPS)-induced mucus secretion and inflammation, and explored the underlying mechanism in vivo and in vitro.</p><p><b>Methods</b>For the in vitro study, human bronchial epithelial (NCI-H292) cells were pretreated with CUR or vehicle for 30 min, and then exposed to LPS for 24 h. Next, nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down with Nrf2 small interfering RNA (siRNA) to confirm the specific role of Nrf2 in mucin regulation of CUR in NCI-H292 cells. In vivo, C57BL/6 mice were randomly assigned to three groups (n = 7 for each group): control group, LPS group, and LPS + CUR group. Mice in LPS and LPS + CUR group were injected with saline or CUR (50 mg/kg) intraperitoneally 2 h before intratracheal instillation with LPS (100 μg/ml) for 7 days. Cell lysate and lung tissue were obtained to measured Mucin 5AC (MUC5AC) and Nrf2 mRNA and protein expression by a real-time polymerase chain reaction and Western blotting. Bronchoalveolar lavage fluid (BALF) was collected to enumerate total cells and neutrophils. Histopathological changes of the lung were observed. Data were analyzed by one-way analysis of variance. Student's t-test was used when two groups were compared.</p><p><b>Results</b>CUR significantly decreased the expression of MUC5AC mRNA and protein in NCI-H292 cells exposed to LPS. This effect was dose dependent (2.424 ± 0.318 vs. 7.169 ± 1.785, t = 4.534, and 1.060 ± 0.197 vs. 2.340 ± 0.209, t = 7.716; both P < 0.05, respectively) and accompanied by increased mRNA and protein expression of Nrf2 (1.952 ± 0.340 vs. 1.142 ± 0.176, t = -3.661, and 2.010 ± 0.209 vs. 1.089 ± 0.132, t = -6.453; both P < 0.05, respectively). Furthermore, knockdown of Nrf2 with siRNA increased MUC5AC mRNA expression by 47.7%, compared with levels observed in the siRNA-negative group (6.845 ± 1.478 vs. 3.391 ± 0.517, t = -3.821, P < 0.05). Knockdown of Nrf2 with siRNA also markedly increased MUC5AC protein expression in NCI-H292 cells. CUR also significantly decreased LPS-induced mRNA and protein expression of MUC5AC in mouse lung (1.672 ± 0.721 vs. 5.961 ± 2.452, t = 2.906, and 0.480 ± 0.191 vs. 2.290 ± 0.834, t = 3.665, respectively; both P < 0.05). Alcian blue/periodic acid-Schiff staining also showed that CUR suppressed mucin production. Compared with the LPS group, the numbers of inflammatory cells (247 ± 30 vs. 334 ± 24, t = 3.901, P < 0.05) and neutrophils (185 ± 22 vs. 246 ± 20, t = 3.566, P < 0.05) in BALF decreased in the LPS + CUR group, as well as reduced inflammatory cell infiltration in lung tissue.</p><p><b>Conclusion</b>CUR inhibits LPS-induced airway mucus hypersecretion and inflammation through activation of Nrf2 possibly.</p>
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<p><b>BACKGROUND</b>Chronic intermittent hypoxia (CIH) has been associated with abnormalities in the liver, which is the most important organ for drug metabolism. This study aimed to investigate the effect of CIH on theophylline metabolism in mouse liver.</p><p><b>METHODS</b>Eight C57BL/6J mice were exposed to CIH for 12 weeks. Eight C57BL/6J mice were exposed to room air as a control group. Serum levels of alanine aminotransferase and aspartate aminotransferase were measured. Liver histology was observed by light and electron microscopy. Total hepatic cytochrome P450 concentration was measured. Hepatocytes were isolated and incubated with 15 mg/ml theophylline for four hours. After incubation, the theophylline concentration in the supernatant was measured and the theophylline metabolism rate was calculated.</p><p><b>RESULTS</b>CIH did not affect the serum transaminase levels. Livers from mice exposed to CIH showed hepatocellular edema, and liver cells had fuzzy rough endoplasmic reticulum under the electron microscope. The theophylline metabolism rate was significantly inhibited by CIH compared with controls; (16.60 ± 2.43)% vs. (21.58 ± 4.52)% (P = 0.02). The total liver cytochrome P450 concentration in the CIH group was significantly lower than in the control group; (0.83 ± 0.08) vs. (1.13 ± 0.21) mol/mg microsomal protein (P = 0.004).</p><p><b>CONCLUSION</b>CIH decreases theophylline metabolism by mouse hepatocytes, which may correlate with the downregulation of cytochrome P450 expression by CIH.</p>
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Animals , Male , Mice , Chronic Disease , Cytochrome P-450 Enzyme System , Physiology , Hepatocytes , Metabolism , Hypoxia , Metabolism , Liver , Metabolism , Mice, Inbred C57BL , Theophylline , MetabolismABSTRACT
<p><b>BACKGROUND</b>Chronic intermittent hypoxia is the most important pathophysiologic feature of sleep apnea syndrome. The present study aimed to determine whether chronic intermittent hypoxia, which is associated with sleep apnea syndrome, can cause or increase damage to liver cell ultrastructure induced by isoniazid and rifampicin in mice.</p><p><b>METHODS</b>Based on a 2 × 2 full factorial design consisting of two factors of chronic intermittent hypoxia and isoniazid plus rifampicin, 32 male C57B6J mice were randomized into the control group, the chronic intermittent hypoxia group, the isoniazid plus rifampicin group, and the chronic intermittent hypoxia + isoniazid plus rifampicin group. Twelve weeks after treatment, we examined the ultrastructure of liver cells and quantitatively analyzed mitochondrial morphology in C57B6J mice.</p><p><b>RESULTS</b>Chronic intermittent hypoxia did not significantly affect the ultrastructure of liver cells. The main effect of chronic intermittent hypoxia did not lead to an increase of mean profile area or mean perimeter of mitochondria, and a decrease of numerical density on area of mitochondria (all P > 0.05). Isoniazid plus rifampicin significantly affected liver cell ultrastructure. The main effect of isoniazid plus rifampicin resulted in an increase of mean profile area and mean perimeter of mitochondria, and a decrease of numerical density on area of mitochondria (all P < 0.05). Moreover, there was a positive interaction among the chronic intermittent hypoxia and the isoniazid plus rifampicin groups for mean profile area, mean perimeter, and numerical density on area of mitochondria (all P < 0.05).</p><p><b>CONCLUSION</b>Chronic intermittent hypoxia and isoniazid plus rifampicin treatment lead to synergistic liver cell ultrastructural injury.</p>
Subject(s)
Animals , Male , Mice , Hypoxia , Drug Therapy , Isoniazid , Therapeutic Uses , Liver , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Rifampin , Therapeutic Uses , Sleep Apnea SyndromesABSTRACT
The Bacillus subtilis Sac B gene with the vacuolar targeting signal sequence driven by 35S promotor was transferred into Lespedeza thunbergii by Agrobacterium mediated method. Total 62 Kan-resistant plants were obtained, of which 5 plants were proved to be transgenic plants. The transgenic plants were characterized by PCR amplification, PCR-Southern hybridization and RT-PCR. The physiological assay results showed that the transgenic plants were more tolerant to stress than the controls under the condition of 200mmol/L NaCl and 5% PEG, respectively, and that the content of soluble sugar in trnsgenic plants was significantly higher than that of controls in the period of tests (5-15 days) under salt and PEG stress.