Growth hormone-releasing peptide 6 prevents cutaneous hypertrophic scarring: early mechanistic data from a proteome study.

Hypertrophic scars (HTS) and keloids are forms of aberrant cutaneous healing with excessive extracellular matrix (ECM) deposition. Current therapies still fall short and cause undesired effects. We aimed to thoroughly evaluate the ability of growth hormone releasing peptide 6 (GHRP6) to both prevent and reverse cutaneous fibrosis and to acquire the earliest proteome data supporting GHRP6's acute impact on aesthetic wound healing. Two independent sets of experiments addressing prevention and reversion effects were conducted on the classic HTS model in rabbits. In the prevention approach, the wounds were assigned to topically receive GHRP6, triamcinolone acetonide (TA), or vehicle (1% sodium carboxy methylcellulose [CMC]) from day 1 to day 30 post-wounding. The reversion scheme was based on the infiltration of either GHRP6 or sterile saline in mature HTS for 4 consecutive weeks. The incidence and appearance of HTS were systematically monitored. The sub-epidermal fibrotic core area of HTS was ultrasonographically determined, and the scar elevation index was calculated on haematoxylin/eosin-stained, microscopic digitised images. Tissue samples were collected for proteomics after 1 hour of HTS induction and treatment with either GHRP6 or vehicle. GHRP6 prevented the onset of HTS without the untoward reactions induced by the first-line treatment triamcinolone acetonide (TA); however, it failed to significantly reverse mature HTS. The preliminary proteomic study suggests that the anti-fibrotic preventing effect exerted by GHRP6 depends on different pathways involved in lipid metabolism, cytoskeleton arrangements, epidermal cells' differentiation, and ECM dynamics. These results enlighten the potential success of GHRP6 as one of the incoming alternatives for HTS prevention.

Pharmacodynamic of Recombinant Human Interferon Alpha-2b Nasal Drops and Effective Prophylaxis Against SARS-COV-2 Infection.

The recombinant human interferon alpha-2b (IFN-α2b) nasal drop formulation (Nasalferon) was studied as prophylaxis for SARS-CoV-2. Healthy volunteers between 19 and 80 years of age received 0.5 million international units of IFN in one drop (0.05 mL ) in each nostril, twice a day, for 10 consecutive days. The nondetection of SARS-CoV-2 by real-time polymerase chain reaction was the primary outcome variable. Several IFN-α biomarkers, including intranasal gene expression and innate immune effector activity, were increased in participants who received intranasal IFN-α2b. The study included 2,930 international travelers and 5,728 persons who were their close contacts. The subjects were treated with Nasalferon in January 2021, and 9,162 untreated travelers were included as controls. COVID-19 rate in treated subjects was significantly lower than in untreated subjects (0.05% vs. 4.84%). The proportion of travelers with COVID-19 decreased from 60.9% to 2.2% between December 2020 and February 2021. Furthermore, 1,719 tourism workers also received Nasalferon, and no cases of SARS-CoV-2 infection were detected, whereas 39 COVID-19 cases (10.6%) were reported in 367 untreated subjects. The main adverse events associated with the use of intranasal IFN-α2b were nasal congestion, headache, and rhinorrhea. Our prophylactic health interventions study demonstrates that the daily administration of Nasalferon for 10 days decreases the risk of developing COVID-19 in healthy volunteers. [Figure: see text].

BioHabana 2022: Preventive and Immunotherapeutic Strategies Against COVID-19 and Cancer in Cuba.

The convergence of life sciences with neurosciences, nanotechnology, data management, and engineering has caused a technological diversification of the biotechnology, pharmaceutical, and medical technology industries, including the phenomenon of digital transformation, which has given rise to the so-called Fourth Industrial Revolution (Industry 4.0). Confronting the COVID-19 pandemic revealed the outstanding response capacity of the scientific community and the biopharmaceutical industry, based on a multidisciplinary and interinstitutional approach that has achieved an unprecedented integration in the history of biomedical science. Cuba, a small country, with scarce material resources, has had remarkable success in controlling the disease, which also highlights the impact of social factors. This report presents a summary of the most relevant presentations of selected topics during the scientific meeting, "BioHabana 2022: Cancer Immunotherapy and the COVID-19 Pandemic," which was held in Havana Cuba in April 2022.

Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds.

In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6) proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmØ) were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit's ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 µg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit's model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARγ and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic.

Recombinant streptokinase vs phenylephrine-based suppositories in acute hemorrhoids, randomized, controlled trial (THERESA-3).

AIM: To compare the efficacy and safety of recombinant streptokinase (rSK) and phenylephrine-based suppositories in acute hemorrhoidal disease. METHODS: A multicenter (14 sites), randomized (1:1), open, parallel groups, active controlled trial was done. After inclusion, subjects with acute symptoms of hemorrhoids, who gave their written, informed consent to participate, were centrally randomized to receive, as outpatients, rSK (200000 IU) or 0.25% phenylephrine suppositories, which had different organoleptic characteristics. Treatment was administered by the rectal route, one unit every 6 h during 48 h for rSK, and up to a maximum of 5 d (20 suppositories) for phenylephrine. Evaluations were performed at 3, 5 and 10 d post-inclusion. The main end-point was the 5(th)-day complete clinical response (disappearance of pain and edema, and ≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were evaluated too. RESULTS: 5(th) day complete response rates were 83/110 (75.5%) and 36/110 (32.7%) with rSK and phenylephrine suppositories, respectively. This 42.7% difference (95%CI: 30.5-54.2) was highly significant (P < 0.001). The advantage was detected since the early 3(rd) day evaluation (37.3% vs 6.4% for the rSK and active control groups, respectively; P < 0.001) and was kept even at the late 10(th) day assessment (83.6% vs 58.2% for rSK and phenylephrine, respectively; P < 0.001). Time for complete response was significantly shorter (P = 0.031; log-rank test) in the rSK group (median: 4.9 d; 95%CI: 4.8-5.0) with respect to the active control (median: 9.8 d; 95%CI: 9.8-10.0). Thrombectomy was necessary in 1/59 and 8/57 patients with baseline thrombosis in the rSK and phenylephrine groups, respectively (P = 0.016). There were no adverse events attributable to the experimental treatment. CONCLUSION: rSK suppositories showed a significant advantage over a widely used over-the-counter phenylephrine preparation for the treatment of acute hemorrhoidal illness, with an adequate safety profile.