THE ROLE OF HMGB1 IN THE IMMUNE RESPONSE TO SARS-COV-2 INFECTION: FROM PATHOGENESIS TOWARDS A NEW POTENTIAL THERAPEUTIC TARGET
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the most important emerging pathogen since it was discovered in late 2019, infecting millions of people worldwide. The human body's defence against this new viral respiratory infection depends on the immune response of each person with a crucial impact on the appearance of clinical signs. Therefore, it is important to identify endogenous molecules with a fundamental role in severe pulmonary inflammation associated with SARS-CoV-2 infection. The impact of high mobility group proteins (HMGBs) in the pathogenesis of coronavirus disease 2019 (COVID-19) was recently proposed. There is also recent evidence that HMGBs, particularly HMGB1–2, play important roles in the replication of viral genomes. Moreover, HMGB1–4 proteins appear to be associated with inflammatory processes in the pathogenesis of many other viral diseases and disorders, including lung disease, ischemia-reperfusion-injury, sepsis, coagulopathy, trauma, neurological disorders, and cancer. This article presents the possible roles of HMGB1 in SARS-CoV-2 replication and its involvement in the pathogenesis of clinical severe pulmonary manifestations;these data can be useful in further virologic studies and the finding of new potential therapeutic targets in COVID-19.
- Citations: 11
- Aug 23, 2021
KEY POINTS IN FERTILITY PRESERVATION TREATMENT STRATEGIES DURING COVID-19 PANDEMIC. AN UPDATE ON PHARMACOLOGICAL THERAPIES
The fertility preservation (FP) field has developed in the two decades and offers women the possibility to have genetic children at some point in life. Fertility preservation is urgent by definition, performed for social reasons or medical indications, such as impending gonadotoxic therapy or radical gynaecological surgery. One year after the pandemic was declared, the COVID-19 infection imposed several restrictions and limited access to health care for the infertile couple. Ovarian stimulation is a pharmacological treatment used to induce the development of ovarian follicles;FP guidelines provide different options for ovarian stimulation. We performed a systematic search on fertility preservation (FP) procedures during the COVID-19 pandemic using the keywords: FP, ovarian stimulation, assisted reproduction techniques (ART), and COVID-19. In order to update the different treatment strategies in ovarian stimulation on fertility preservation studied in the last ten years, we searched for randomized clinical trials (RCTs) focused on therapeutic agents used in current protocols, gonadotropins, gonadotropin releasing hormone (GnRH), clomiphene citrate (CC), letrozole, androgens, metformin, tamoxifen, glucocorticoids, aspirin, coenzyme Q10, and sildenafil. Fertility may be influenced by SARS-CoV-2 infection - especially in men;until more evidence confirms the effects on fertility, patients with COVID-19 positive should delay FP procedures if possible. Access to fertility conservation services decreased during the analysed period due to the medical services restrictions and the reorientation of medical resources on patients with COVID-19, without major changes in the current therapeutic protocols. In terms of pharmacotherapy in ovarian stimulation (OS) procedures, letrozole is first line therapy, superior to CC for OS. Similar ovulation and pregnancy rate can be obtained in letrozole - induced ovulation compared to gonadotropin protocol. Adjuvant therapies may be used for OS but lack proven efficacy. Further studies on adjuvant therapies and complementary support are needed, to ensure optimal condition in assisted reproductive interventions for fertility preservation, especially in gonadotoxic therapies.
- Citations: 3
- Apr 25, 2021
IN VITRO AND EX VIVO STUDIES ON ANGIOTENSIN-I CONVERTING ENZYME (ACE) INHIBITORY ACTIVITY OF SHORT SYNTHETIC PEPTIDES
In our days the interest in the studies of new angiotensin-converting-enzyme (ACE) inhibitors as modulators of the renin-angiotensin-system (RAS) is growing, not only because of their importance as drugs for arterial hypertension treatment, but also for their therapeutic potential during COVID-19 infection. This study presents data for the design and synthesis of short peptides by SPPS strategy and investigates in vitro and ex vivo their potential as ACE inhibitors in the light of structural changes. The obtained results give insight into the structure-activity relationship of peptide sequences and show differences regarding the effects of peptides in two experimental procedures (inhibitory potency on purified ACE activity and AT-I induced rat ileum contractions). Three of the newly synthesized peptides with terminal proline, LAP, LKP and VAP, showed relatively high inhibitory activities.
- Citations: 0
- Apr 20, 2021
HEALTH CARE DIGITALIZATION, THE STRAIGHTEST PATHWAY TO PERSONALIZATION
Digitalization appears as a full mutation in the entire world, including health care. From applications (apps) to sensors, the digital is now fully integrated in daily life for patients. Monitoring treatments more easily and improving the design for drug packaging remain the most challenging points for medicines and the digitalization appears as a useful alternative. An overview of some relevant proposals that integrates personalization to users and drug forms is proposed with a specific focus on cardiology treatments and COVID-19 innovations.
- Citations: 4
- Apr 20, 2021
GASTROPROTECTIVE ACTIVITY OF EQUISETUM HYEMALE IN EXPERIMENTAL GASTRIC ULCER RAT MODELS
Equisetum hyemale is traditionally used for dyspepsia and stomach pain. The aim of the present study was to evaluate the gastroprotective activity of the aqueous ethanolic extract of the aerial parts of Equisetum hyemale in gastric ulcer rat models. Gastric ulcer models were induced by ethanol (5 mL/kg bw), acetylsalicylic acid (ASA) (200 mg/kg bw) and pylorus ligation separately. The pH, total acidity, ulcer scoring index and histopathological evaluation were performed. Oral administration of Equisetum hyemale extract (250 and 500 mg/kg bw) significantly reduced the development of gastric lesions in all gastric ulcer models. The pH, total acidity and ulcer scoring index also decreased significantly when compared with the Diseased control group. Histopathological studies are in good agreement with the biochemical findings. Equisetum hyemale might show its gastroprotective activity by decreasing oxidative damage, blockage of H2 receptors activation, increase prostaglandins secretion and formation of mucus layer in different gastric ulcer models. The findings of the present study validate the traditional use of Equisetum hyemale to treat stomach pain, however the determination of phytochemical compounds responsible for gastroprotective activity is required for further confirmation.
- Citations: 1
- Apr 20, 2021