Idiopathic pulmonary fibrosis (IPF) is characterized by fibroblast expansion and extracellular matrix accumulation. However, the mechanisms involved in matrix remodeling have not been elucidated. In this study, the authors aimed to evaluate the expression of the tissue inhibitors of matrix metalloproteinases (TIMPs) in human fibroblasts and whole tissues from IPF and normal lungs. They also determined the role of mitogen-activated protein kinase (MAPK) in TIMP3 expression. TIMP1, TIMP2, and TIMP3 were highly expressed in lung fibroblasts. Transforming growth factor (TGF)-β1, a profibrotic mediator, induced strong up-regulation of TIMP3 at the mRNA and protein levels. The authors examined whether the MAPK pathway was involved in TGF-β1–induced TIMP3 expression. TGF-β1 induced the phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2. Biochemical blockade of p38 by SB203580, but not of the ERK MAPK pathway, inhibited the effect of this factor. The effect was also blocked by the tyrosine kinase inhibitor genistein and by antagonizing TGF-β1 receptor type I (activin-linked kinase [ALK5]). In IPF tissues TIMP3 gene expression was significantly increased and the protein was localized to fibroblastic foci and extracellular matrix. Our findings suggest that TGF-β1–induced TIMP3 may be an important mediator in lung fibrogenesis.

AIM: To assess expression of matrix metalloproteinases 2 (MMP2) and MMP9 in gastric cancer, superficial gastritis and normal mucosa, and to measure metalloproteinase activity. METHODS: MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction. Normalization was carried out using three different factors. Proteins were analyzed by quantitative gelatin zymography (qGZ). RESULTS: 18S ribosomal RNA (18SRNA) was very highly expressed, while hypoxanthine ribosyltransferase-1 (HPRT-1) was moderately expressed. MMP2 was highly expressed, while MMP9 was not detected or lowly expressed in normal tissues, moderately or highly expressed in gastritis and highly expressed in cancer. Relative expression of 18SRNA and HPRT-1 showed no significant differences. Significant differences in MMP2 and MMP9 were found between cancer and normal tissue, but not between gastritis and normal tissue. Absolute quantification of MMP9 echoed this pattern, but differential expression of MMP2 proved conflictive. Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2, total MMP-9, 250 and 110 kDa bands. CONCLUSION: MMP9 expression is enhanced in gastric cancer compared to normal mucosa; interpretation of differential expression of MMP2 is difficult to establish.

Background: The disease Zika is considered as emergent. The infection can be acquired through different routes: a bite from the Aedes mosquito, sexual contact, from mother to child during pregnancy and by blood transfusion. The possibility of Zika transmission through human lactation has been considered. Zika is a disease of great concern for public health because it has been associated with neonatal and postnatal microcephaly, among other birth defects. Objectives: To review published evidence of the probable transmission of Zika through human lactation. Data sources: Electronic databases: Cochrane Central Register of Controlled Trials, EBSCO, Gale, Science Direct, Scopus, US National Library of Medicine (PubMed) and Web of Science. World Health Organization and Centers for Disease Control and Prevention web pages. Study eligibility criteria: To be eligible, studies of any design had to provide primary data of human breast milk as a potential fluid for the transmission of Zika, or primary or secondary follow-up data of infants with at least one previous published study that complied with the first criterion of eligibility. Participants: Studies about women with suspected, probable or confirmed Zika during pregnancy, or the postnatal period and beyond. Studies about infants who breastfeed directly from the breast or where fed with the expressed breast milk of the suspected, probable or confirmed women with Zika. Results: This study only chose data from research papers; no patients were taken directly by the authors. A total of 1,146 were screened and nine studies were included in the qualitative synthesis, from which a total of 10 cases were identified, with documented follow-up in three of these cases. Through the timing of maternal Zika infection, five cases were classified as prenatal (time before delivery), one as immediate postnatal (period from 0 to 4 days after birth); no cases were classified as medium postnatal (period from 5 days to 8 weeks after birth); two were classified as long postnatal (period from 8 weeks to 6 months after birth) and two as beyond six months after birth. Conclusion: Human milk may be considered as a potentially infectious fluid, but we found no currently documented studies of the long-term complications in infants up to 32 months of age, with suspected, probable or confirmed Zika through human lactation, or evidence with respect to the human pathophysiology of the infection acquired through human lactation. In the light of the studies reviewed here, the World Health Organization recommendation of June 29th 2016, remains valid: “the benefits of breastfeeding for the infant and mother outweigh any potential risk of Zika virus transmission through breast milk.”