Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model.

Although the exact mechanism of the pathogenesis of coronavirus SARS-CoV-2 (COVID-19) is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the level of inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red photobiomodulation (PBM) as an attractive therapy to downregulate the cytokine storm caused by COVID-19 in a zebrafish model. RT-qPCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a and coa1) mRNA markers, with a pattern similar to those observed in COVID-19 cases in humans. On the other hand, PBM treatment was able to decrease the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most-impacted metabolic pathways between PBM and the rSpike treated groups were related to steroid metabolism, immune system, and lipid metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19 and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials can commence.

The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

OBJECTIVES: Activators of soluble guanylyl cyclase (sGC) act preferentially in conditions of enzyme oxidation or haem group removal. This study was designed to investigate the effects of the sGC activator BAY 60-2770 in murine airways inflammation and human eosinophil chemotaxis. METHODS: C57Bl/6 mice treated or not with BAY 60-2770 (1 mg/kg/day, 14 days) were intranasally challenged with ovalbumin (OVA). At 48 h, bronchoalveolar lavage fluid (BALF) was performed, and circulating blood, bone marrow and lungs were obtained. Human eosinophils purified from peripheral blood were used to evaluate the cell chemotaxis. RESULTS: OVA-challenge promoted marked increases in eosinophil number in BAL, lung tissue, circulating blood and bone marrow, all of which were significantly reduced by BAY 60-2770. The IL-4 and IL-5 levels in BALF were significantly reduced by BAY 60-2770. Increased protein expression of iNOS, along with decreases of expression of sGC (α1 and ß1 subunits) and cGMP levels were detected in lung tissue of OVA-challenged mice. BAY 60-2770 fully restored to baseline the iNOS and sGC subunit expressions, and cGMP levels. In human isolated eosinophils, BAY 60-2770 (1-5 µM) had no effects on the cGMP levels and eotaxin-induced chemotaxis; however, prior incubation with ODQ (10 µM) markedly elevated the BAY 60-2770-induced cyclic GMP production, further inhibiting the eosinophil chemotaxis. CONCLUSIONS: BAY 60-2770 reduces airway eosinophilic inflammation and rescue the sGC levels. In human eosinophils under oxidized conditions, BAY 60-2770 elevates the cGMP levels causing cell chemotaxis inhibition. BAY 60-2770 may reveal a novel therapeutic target for asthma treatment.

Ectopic Intrathyroidal Parathyroid Adenoma Presenting With Osteoporotic Fractures in a Young Man: A Case Report.

Primary hyperparathyroidism (PHPT) can be associated with osteoporosis (OP) and fractures. We present a case of a 49-year-old male referred to our osteoporosis outpatient clinic due to a right femur osteoporotic fracture. At the age of 38, a right plantar nodular lesion was excised, and its histology was compatible with a deep dermis nodule formed by mononuclear and giant osteoclast-like cells. He has reported osteoporotic fractures since age 39 and renal colic episodes since age 45. His father had lipomas and renal colic episodes, and his paternal grandmother had lipomas. The laboratory evaluation was compatible with PHPT. A cervical ultrasound showed a 10mm single solid nodule in the left thyroid lobe, strongly hypoechogenic, with microcalcifications. Its cytology showed parathyroid tissue without atypia. Parathyroid scintigraphy had no uptake. A dual-energy X-ray absorptiometry scan showed a femoral neck Z-score of -4.3. He started alendronate/cholecalciferol (70mg/5600IU) weekly. He was submitted to a left hemithyroidectomy. Its histology showed an intrathyroidal parathyroid adenoma. Ectopic parathyroid adenomas are rare, of which 0.7%-6% are intrathyroidal. The excised foot lesion could be a brown tumour. Furthermore, calcium metabolism evaluation at that time might have allowed a PHPT diagnosis and its morbidity prevention. Osteoporotic fractures in young men must alert to secondary OP.

Tamoxifen associated to the conservative CKD treatment promoted additional antifibrotic effects on experimental hypertensive nephrosclerosis.

CKD progression depends on the activation of an intricate set of hemodynamic and inflammatory mechanisms, promoting renal leukocyte infiltration, inflammation and fibrosis, leading to renal function loss. There are currently no specific drugs to detain renal fibrogenesis, which is a common end-point for different nephropathies. Clinical therapy for CKD is mostly based on the management of hypertension and proteinuria, partially achieved with renin-angiotensin-aldosterone system (RAAS) blockers, and the control of inflammation by immunosuppressive drugs. The aim of the present study was to verify if the administration of tamoxifen (TAM), an estrogen receptor modulator, clinically employed in the treatment of breast cancer and predicted to exert antifibrotic effects, would promote additional benefits when associated to a currently used therapeutic scheme for the conservative management of experimental CKD. Wistar rats underwent the NAME model of hypertensive nephrosclerosis, obtained by daily oral administration of a nitric oxide synthesis inhibitor, associated to dietary sodium overload. The therapeutic association of TAM to losartan (LOS), and mofetil mycophenolate (MMF) effectively reduced the severe hypertension, marked albuminuria and glomerular damage exhibited by NAME animals. Moreover, the association also succeeded in limiting renal inflammation in this model, and promoted further reduction of ECM interstitial accumulation and renal fibrosis, compared to the monotherapies. According to our results, the association of TAM to the currently used conservative treatment of CKD added significant antifibrotic effects both in vivo and in vitro, and may represent an alternative to slow the progression of chronic nephropathy.

Immunization with SARS-CoV-2 Nucleocapsid protein triggers a pulmonary immune response in rats.

The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection.

Promoting Self-Regulation in Health Among Vulnerable Brazilian Children: Protocol Study.

The Health and Education Ministries of Brazil launched the Health in School Program (Programa Saúde na Escola - PSE) in 2007. The purpose of the PSE is two-fold: articulate the actions of the education and health systems to identify risk factors and prevent them; and promote health education in the public elementary school system. In the health field, the self-regulation (SR) construct can contribute to the understanding of life habits which can affect the improvement of individuals' health. This research aims to present a program that promotes SR in health (SRH). This program (PSRH) includes topics on healthy eating and oral health from the PSE; it is grounded on the social cognitive framework and uses story tools to train 5th grade Brazilian students in SRH. The study consists of two phases. In Phase 1, teachers and health professionals participated in a training program on SRH, and in Phase 2, they will be expected to conduct an intervention in class to promote SRH. The participants were randomly assigned into three groups: the Condition I group followed the PSE program, the Condition II group followed the PSRH (i.e., PSE plus the SRH program), and the control group (CG) did not enroll in either of the health promotion programs. For the baseline of the study, the following measures and instruments were applied: Body Mass Index (BMI), Simplified Oral Hygiene Index (OHI-S), Previous Day Food Questionnaire (PFDQ), and Declarative Knowledge for Health Instrument. Data indicated that the majority are eutrophic children, but preliminary outcomes showed high percentages of children that are overweight, obese and severely obese. Moreover, participants in all groups reported high consumption of ultraprocessed foods (e.g., soft drinks, artificial juices, and candies). Oral health data from the CI and CII groups showed a prevalence of regular oral hygiene, while the CG presented good oral hygiene. The implementation of both PSE and PSRH are expected to help reduce health problems in school, as well as the public expenditures with children's health (e.g., Obesity and oral diseases).