LY3041658/ interleukin-8 complex structure as targets for IL-8 small molecule inhibitors discovery using a combination of in silico methods.

Since interleukin-8 (IL-8/CXCL8) and its receptor, CXCR1 and CXCR2, were known in the early 1990s, biological pathways related to these proteins were proven to have high clinical value in cancer and inflammatory/autoimmune conditions treatment. Recently, IL-8 has been identified as biomarker for severe COVID-19 patients and COVID-19 prognosis. Boyles et al. (mAbs 12 (2020), pp. 1831880) have published a high-resolution X-ray crystal structure of the LY3041658 Fab in a complex human CXCL8. They described the ability to bind to IL-8 and the blocking of IL-8/its receptors interaction by the LY3041658 monoclonal antibody. Therefore, the study has been designed to identify potential small molecules inhibiting interleukin-8 by targeting LY3041658/IL-8 complex structure using an in silico approach. A structure­based pharmacophore and molecular docking models of the protein active site cavity were generated to identify possible candidates, followed by virtual screening with the ZINC database. ADME analysis of hit compounds was also conducted. Molecular dynamics simulations were then performed to survey the behaviour and stability of the ligand-protein complexes. Furthermore, the MM/PBSA technique has been utilized to evaluate the free binding energy. The final data confirmed that one newly obtained compound, ZINC21882765, may serve as the best potential inhibitor for IL-8.

Development of Novel Riboswitches for Synthetic Biology in the Green Alga Chlamydomonas.

Riboswitches are RNA regulatory elements that bind specific ligands to control gene expression. Because of their modular composition, where a ligand-sensing aptamer domain is combined with an expression platform, riboswitches offer unique tools for synthetic biology applications. Here we took a mutational approach to determine functionally important nucleotide residues in the thiamine pyrophosphate (TPP) riboswitch in the THI4 gene of the model alga Chlamydomonas reinhardtii, allowing us to carry out aptamer swap using THIC aptamers from Chlamydomonas and Arabidopsis thaliana. These chimeric riboswitches displayed a distinct specificity and dynamic range of responses to different ligands. Our studies demonstrate ease of assembly as 5'UTR DNA parts, predictability of output, and utility for controlled production of a high-value compound in Chlamydomonas. The simplicity of riboswitch incorporation in current design platforms will facilitate the generation of genetic circuits to advance synthetic biology and metabolic engineering of microalgae.

Management of radiation-induced ulcers by singlestage reconstructive surgery: a prospective study.

Radiation-induced ulcers are a late-stage skin reaction after radiation therapy for cancer treatment. The present study examined the possibility of using a single-stage reconstructive procedure to manage radiation-related wounds. This prospective study recruited 30 participants who underwent radiation treatment for cancer or hemangioma. The patients ranged in age from 15 to 80 years. They were admitted to the Plastic, Reconstructive, and Regenerative Centre of Viet Nam National Burn Hospital from October 2013 to September 2017. For each patient, the surgeons discussed which reconstructive method would yield the best outcome. Patients' demographic data and information on the radiation-induced ulcer, the reconstructive method used, complications, and length of hospital stay were recorded. The mean age of all participants was 50 ± 36.3 years, and female patients were predominant (83.3%). Eighteen perforator flaps, five random-pattern flaps, three free flaps, three tissue expander flaps, and one full-thickness skin graft were employed, with no instances of recurrence or complications, except for total flap loss in two cases. The median length of stay was 43 days. These data suggest that immediate reconstruction may be a valuable option for managing radiation-induced ulcers.

Les radiodermites chroniques ulcéreuses sont une complication tardive des radiothérapies pour cancer. Cette étude prospective, réalisée dans le service de chirurgie plastique, reconstructive et régénérative de l'hôpital brûlologique national du Viêtnam d'octobre 2013 à septembre 2017, a examiné la possibilité de leur reconstruction en un seul temps chirurgical. Elle a concerné 30 patients irradiés pour cancer ou hémangiome, la meilleure méthode de reconstruction ayant à chaque fois été recherchée par le chirurgien. Les données démographiques, celles de la lésion, la méthode de reconstruction choisie, la durée de séjour et les complications ont été colligées. L'âge moyen était de 50 +/- 36,3 ans (15 ­ 80) et l'échantillon comprenait 83,3% de femmes. Nous avons réalisé 18 lambeaux perforants, 5 lambeaux au hasard, 3 lambeaux libres, 3 lambeaux après expansion et 1 greffe de peau totale. Deux lambeaux ont complétement nécrosé, il n'y a pas eu de récidive. La durée médiane de séjour était de 45 j. La reconstruction en 1 temps semble donc être possible dans le traitement des radiodermites chroniques.

Temporal and spatial association of Streptococcus suis infection in humans and porcine reproductive and respiratory syndrome outbreaks in pigs in northern Vietnam.

Porcine reproductive and respiratory syndrome (PRRS) outbreaks in pigs are associated with increased susceptibility of pigs to secondary bacterial infections, including Streptococcus suis - an important zoonotic pathogen causing bacterial meningitis in humans. This case-control study examined the association between human S. suis infection and PRRS outbreaks in pigs in northern Vietnam. We included 90 S. suis case-patients and 183 non-S. suis sepsis controls from a referral hospital in Hanoi in 2010, a period of major PRRS epizootics in Vietnam. PRRS exposure was determined using data from the National Centre of Veterinary Diagnosis. By univariate analysis, significantly more S. suis patients were reported residing in or adjacent to a PRRS district compared to controls [odds ratio (OR) 2·82, 95% confidence interval (CI) 1·35-5·89 and OR 3·15, 95% CI 1·62-6·15, respectively]. Only residency in adjacent districts remained significantly associated with risk of S. suis infection after adjusting for sex, occupation, and eating practices. SaTScan analysis showed a possible cluster of S. suis infection in humans around PRRS confirmed locations during the March-August period. The findings indicate an epidemiological association between PRRS in pigs and S. suis infections in humans. Effective strategies to strengthen control of PRRS in pigs may help reduce transmission of S. suis infection to humans.