Artesunate ameliorates irinotecan-induced intestinal injury by suppressing cellular senescence and significantly enhances anti-tumor activity.

Irinotecan (CPT-11) is a topoisomerase I inhibitor that was approved for cancer treatment in 1994. To date, this natural product derivative remains the world's leading antitumor drug. However, the clinical application of irinotecan is limited due to its side effects, the most troubling of which is intestinal toxicity. In addition, irinotecan has certain toxicity to cells and even causes cellular senescence. Committed to developing alternatives to prevent these adverse reactions, we evaluated the activity of artesunate, which has never been tested in this regard despite its biological potential. Irinotecan accelerated the process of aging in vivo and in vitro, and we found that this was mainly caused by activating mTOR signaling targets. Artesunate inhibited the activity of mTOR, thereby alleviating the aging process. Our study found that artesunate treatment improved irinotecan-induced intestinal inflammation by reducing the levels of TNF-α, IL1, and IL6; reducing inflammatory infiltration of the colonic ileum in mice; and preventing irinotecan-induced intestinal damage by reducing weight loss and improving intestinal length. In addition, in mouse xenograft tumor models, artesunate and irinotecan significantly inhibited tumor growth in mice.

MicroRNAs are potential regulators of the timed artificial insemination effect in gilt endometrium.

To determine effects of timed artificial insemination (TAI) hormonal treatments on reproductive performance of gilts/sows and explore molecular mechanisms, gilts (TAI: 90; Control:149; Total: 239) and sows (TAI: 370; Control: 492) were utilized. Results indicated the estrus/farrowing rate and number of piglets born alive and weaned in the TAI group were greater than in the control group for both gilts and sows. To explore the molecular mechanism for TAI hormonal effects, the small RNA of the gilt endometrium at 16 and 25 of gestation were sampled and sequenced to determine potential functions of microRNA (MiRNA); 358 known and 142 novel MiRNAs were detected. With comparison of TAI and control groups, there were 54 differentially abundant MiRNAs, and functional analysis results indicated "binding," "protein/ion binding," and "immune response" were mostly enriched. In addition, representative MiRNAs were selected based on criteria including being regulated on both day 16 and 25 of gestation (ssc-miR-10a-5p, ssc-miR-345-5p, ssc-miR-370) along with reproduction-related target genes (ssc-miR-424-5p, ssc-miR-142-5p). Furthermore, target genes of selected MiRNAs were screened, and functional enrichment of those genes also indicated that the "binding" and "immune response" were mainly enriched. Results from the present study confirmed TAI-hormonal treatments improved estrous/farrowing rate and number of piglets born alive/weaned of gilts/sows and that hormonal treatment regimens leading to behavioral estrus at timed artificial insemination in gilts results in microRNA patterns in the endometrium that are more supportive of pregnancy. Results contribute valuable information for future studies of effects of TAI hormonal treatments on pig reproductive performance.

Preliminary Study on Drug Susceptibility Profile and Resistance Mechanisms to Macrolides of Clinical Isolates of Non-tuberculous Mycobacteria from China.

OBJECTIVE: Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria (NTM) isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. METHODS: Four macrolides, including clarithromycin (CLAR), azithromycin (AZM), roxithromycin (ROX), and erythromycin (ERY), were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23S rRNA and erm, were analyzed with nucleotide sequence analysis. RESULTS: Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191A and T2221C on rrl were specific for the M. abscessus complex (MABC). Seven sites, G2140A, G2210C, C2217G, T2238C, T2322C, T2404C, and A2406G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192G, T2358G, and A2636G, were observed only in M. fortuitum and one site G2152A was specific for M. gordonae. The genes erm(39) and erm(41) were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar. CONCLUSION: The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23S rRNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.

[Molecular subtyping of Vibrio cholerae isolates from outbreaks of cholera by pulsed-field gel electrophoresis in Hainan in 2008].

OBJECTIVE: To analyze the molecular characteristics and genetic correlations of Vibrio cholerae isolates in Hainan in 2008, so as to provide pathogenic proof to diagnose the plague. METHODS: Seventy six cholera strains were isolated from this cholera epidemic.69 strains were obtained from patients, 7 were isolated from external environment, among which, one was from patient's toilet, one from water sample, three were isolated from fish pond near patient's home, one came from swab of the patient vomit on the ground of health center and one from swab of kitchen knife from Hainan University canteen respectively. With conventional aetiological methods, pulse-field gel electrophoresis was conducted and the patterns of the 76 isolates were analyzed. The PFGE image was analyzed using BioNumerics (Version4.0, Applied Maths BVBA, Belium). Image bands were identified and similarity coefficient was automatically generated. RESULTS: Seventy six strains were isolated from Vibrio cholerae outbreaks in Hainan in 2008.5 PFGE patterns of patient's isolates in June were the same, sharing a similarity coefficient of 100%. 70 PFGE patterns of patients and water in October and November were completely same, the similarity coefficient being 100%. But they were not same as that of June. 1 PFGE pattern of isolate from the sample in Hainan University was different, only sharing a similarity coefficient of 79.7%, which showed no correlation with the outbreak. CONCLUSION: Different outbreaks of Vibrio cholera occurred in Hainan in 2008. The epidemic in October and November at different counties was one outbreak. The pollution of water in environment was an important factor for outbreak.