Blue photobiomodulation LED therapy impacts SARS-CoV-2 by limiting its replication in Vero cells

The study of any intervention able to counteract SARS-CoV-2 pandemic is considerably envisaged. It was previously shown, in in vitro models of infections, that the LED blue light is able to decrease the viral load of HSV-1 and ZIKV. In our study, LED photobiomodulation therapy (PBMT) at blue wavelengths (450, 454 and 470 nm) was tested in an in vitro model of SARS-CoV-2 infection, employing three experimental settings: SARS-CoV-2 was irradiated and then transferred to cells; already infected cells were irradiated; cells were irradiated prior to infection. A decrement of the viral load was observed when previously infected cells were irradiated with all three tested wavelengths and relevant effects were registered especially at 48 hours post-infection, possibly suggesting that the blue light could interfere with the intracellular viral replication machinery. Our in vitro findings could represent the starting point for translational applications of PBMT as a supportive approach to fight SARS-CoV-2.     

Breakdown of cartilage proteoglycan in a tissue culture model of rheumatoid arthritis

Proteoglycan breakdown was studied in a coculture model which mimics the confrontation between synovium and cartilage that occurs in rheumatoid arthritis. Bovine nasal-septum cartilage discs radioactively labeled (³⁵SO₄^2? with or without [³H]glucosamine) and ‘chased’ in non-radioactive medium were cultured in contact with minced rheumatoid synovial membranes for intervals up to 8 days. Synovium-stimulated (2–3 fold) cartilage breakdown was unaffected by ascorbate supplementation. Labeled products (small molecules plus proteoglycan complexes) in culture media were characterized by chromatographic, sedimentation and enzymic digestion methods. Breakdown was dominated by the release of a range of proteoglycan products, fully disaggregated and incapable of reaggregation with added hyaluronate. Because constituent glycosaminoglycans were of uniform size, proteoglycan polydispersity was attributed to differences in core protein length. Hydrocortisone inhibited degradation and partially prevented the shift of proteoglycans to lower average molecular weight. An additional breakdown pattern occasionally noted during the initial 48 h of coculture was characterized by release of a subpopulation of low charge-density proteoglycan bearing shortened glycosaminoglycan chains, consistent with glycosidase action. We conclude that rheumatoid synovia exhibit two distinct cartilage degradative potencies in vitro that may be important in vivo: (a) A variable hyaluronidase-like activity at early culture times, and (b) a dominant proteolytic activity generating an array of disaggregated proteoglycann products that differ largely on the basis of their core lengths. The response to hydrocortisone is consistent with inhibition of proteolysis through the stabilization of cellular membranes.     

Ceruloplasmin serum level in post-menopausal women treated with oral estrogens administered at different times.

The liver is an estrogen-responsive organ and the administration of estrogens in humans increases the hepatic synthesis of many proteins. The existence of a circadian rhythm of estrogen receptors in the liver has been proved by different authors. We studied the presence of a different responsiveness of the human liver to the estrogens in two groups of post-menopausal women by evaluating the changes in ceruloplasmin serum level. Conjugated equine estrogens were administered at different times (A: 8 a.m. and B: 8 p.m.). The replacement therapy increased ceruloplasmin serum levels both in group A and B, but the increase was higher in group B than in group A. These data reflect indirectly the presence of a circadian rhythm of hepatic responsiveness to the estrogens.     

Immunoglobulin A Targets a Unique Subset of the Microbiota in Inflammatory Bowel Disease

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Adenocarcinoma of the human exocrine pancreas: presence of secretin and caerulein receptors

We have measured the cytochrome compositions of subfractions derived from appressed and non-appressed thylakoids by centrifugation and aqueous two-phase partition. Cytochrome $\text{b}$-559 (HP) was not detectable in the fraction derived from non-appressed thylakoids. Cytochromes $\text{f}\text{,}\text{b}$-563 and $\text{b}$-559 (LP) were all evenly distributed throughout the thylakoid membrane. This distribution points to plastocyanin as a possible lateral shuttle of reducing equivalents between spatially separated photosystems.Cytochrome $\text{f}$ was accessible to externally added plastocyanin in the inside-out vesicles but not in vesicles of normal sidedness. This strongly supports a location at the inner side of the thylakoid membrane. Cytochrome $\text{b}$-563 was slowly reduced by dithionite in vesicles with both normal and inside-out orientation suggesting a location within the membrane interior.     

Une forme de cryptorchidie d’origine génétique: le syndrome de persistance des canaux de Müller

Persistent Müllerian duct syndrome (PMDS), a rare form of male peudohermaphrodism, is characterized by lack of regression of Müllerian derivatives. These patients are externally phenotypic males in whom the presence of a uterus and Fallopian tubes is discovered during surgical correction of cryptorchidism and/or inguinal hernia. Molecular studies, in a total of 76 PMDS families, were performed by automatic sequencing after amplification by polymerase chain reaction (PCR) of different parts of the gene. AMH, synthesized by Sertoli cells, is a member of the Transforming Growth Factor-β superfamily. The 560 amino-acid glycoprotein is formed by two 70 kDa monomers linked by disulfide bonds. This hormone is cleaved at a proteolytic site 109 amino acids upstream of the C-terminus, yielding the bioactive C-terminal domain and a N-terminus which is not itself bioactive, but which enhances the bioactivity of the C-terminus. The gene, composed of five exons, is located on chromosome 19 (band p13.3). AMH gene mutations are present on the whole length of the gene in 47% of PMDS families. Sixty-one per cent were homozygous due to a high proportion of patients from Arabic or Mediterranean countries, characterized by a high rate of consanguinity. The serum AMH level, assessed by a commercially available enzyme immunoassay technique (ELISA), is extremely low in the great majority of patients, even before puberty when AMH levels are normally high. AMH binds to two distinct membrane-bound receptors, both serine/threonine kinases. The type II AMH receptor (AMHR-II) binds to the ligand, and this complex recruits receptor type I, which acts as a signal transducer by activating specific cytoplasmic substrates, the Smad molecules. AMHR-II, coded by a 8 kbp gene on chromosome 12 (band q13), contains 11 exons. Exons 1–3 encode the extracellular domain, exon 4 encodes the transmembrane part and exons 5–11 encode the intracellular serine/threonine kinase domain. An AMHR-II mutation was detected in 38% of PMDS families, characterized by a normal AMH level for the patient’s age. A particular mutation, a deletion of 27 bp in exon 10, was present in 45% of families of this group. No mutation of either AMH or the AMHR-II gene could be detected in 11 PMDS families.     

Effect of near-infrared and blue laser light on vero E6 cells SARS-CoV-2 infection model

Photobiomodulation therapy (PBMT) employing laser light has been emerging as a safe strategy to challenge viruses. In this study the effect of blue and near-infrared (NIR) laser light was assessed in an in vitro model of SARS-CoV-2 infection. PBMT at blue wavelength inhibited viral amplification when the virus was directly irradiated and then transferred to cell culture and when cells already infected were treated. The NIR wavelength resulted less efficacious showing a minor effect on the reduction of the viral load. The cells receiving the irradiated virus or directly irradiated rescued their viability to level comparable to not treated cells. Virion integrity and antigenicity were preserved after blue and NIR irradiation, suggesting that the PBMT antiviral effect was not correlated to viral lipidic envelope disruption. Our results suggested that PBMT can be considered a valid strategy to counteract SARS-CoV-2 infection, at least in vitro.