Evaluation of patients treated by telemedicine in the beginning of the COVID-19 pandemic in São Paulo, Brazil: A non-randomized clinical trial preliminary study.

We performed a pilot open-label, non-randomized controlled clinical trial in a clinic in São Paulo, Brazil in the beginning of the COVID-19 pandemic. "This medical pilot project was carried out during the pandemic of a new and unknown agent. It was necessary to find a new and safe therapeutic approach for pathogens with high potential for severity and contamination. The repositioning of safe and accessible pre-existing and approved medications and the telemedicine approach improved treated covid patients' symptoms and reduced the risk of disease transmission. The emergency application of a new medical technology was the major limitation of the study. This innovative care model is a low-cost safe strategy, and we understand that applicability can be expanded to other regions in emergency situations." The 187 patients of the study (mean age of 37.6 ± 15,6 years) were divided into four groups: (1) asymptomatic, (2) mild symptoms, (3) moderate symptoms and (4) severe symptoms and were followed up for five days. A drug intervention was performed in group 3 and the patients of Group 4 were oriented to seek hospital care. Of all the patients, 23.0% were asymptomatic, 29.4% reported mild symptoms, 43.9% moderate symptoms and 3.7% severe symptoms. Three patients were hospitalized and discharged after recovery. Our results indicate that the use of telemedicine with diagnosis and drug treatment is a safe and effective strategy to reduce overload of health services and the exposure of healthcare providers and the population. The patients that initiated the treatment in the early stages of the disease presented satisfactory clinical response, reducing the need of face-to-face consultations and hospitalizations. The patients who followed the protocol treatment for COVID-19 with hydroxychloroquine and azithromycin for five days presented statistically significant improvement of clinical symptoms when compared to moderate patients who opted for not following the protocol (p < 0.05) and to all no treatment patients (p < 0.001).

A Reductionist Approach Using Primary and Metastatic Cell-Derived Extracellular Vesicles Reveals Hub Proteins Associated with Oral Cancer Prognosis.

Oral squamous cell carcinoma (OSCC) has high mortality rates that are largely associated with lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Extracellular vesicles (EVs) are membrane-bound particles that play a role in intercellular communication and impact cancer development and progression. Thus, profiling EVs would be of great significance to decipher their role in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of EVs derived from human primary tumor (SCC-9) cells and matched lymph node metastatic (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 63 lipids differentially abundant between LN1 cell- and SCC-9 cell-derived EVs. A multi-omics integration identified 11 'hub proteins' significantly decreased at the metastatic site compared with primary tumor-derived EVs. We confirmed the validity of these findings with analysis of data from multiple public databases and found that low abundance of seven 'hub proteins' in EVs from metastatic lymph nodes (ALDH7A1, CAD, CANT1, GOT1, MTHFD1, PYGB, and SARS) is correlated with reduced survival and tumor aggressiveness in patients with cancer. In summary, this multi-omics approach identified proteins transported by EVs that are associated with metastasis and which may potentially serve as prognostic markers in OSCC.

Prognostic biomarkers in oral squamous cell carcinoma: A systematic review.

Over the years, several tumor biomarkers have been suggested to foresee the prognosis oral squamous cell carcinoma (OSCC) patients. Here, we present a systematic review to identify, evaluate and summarize the evidence for OSCC reported markers. Eligible studies were identified through a literature search of MEDLINE/PubMed until January 2016. We included primary articlesreporting overall survival, disease-free survival and cause-specific survival as outcomes. Our findings were analysed using REporting recommendations for tumor MARKer prognostic studies (REMARK), QuickGo tool and SciCurve trends. We found 41 biomarkers, mostly proteins evaluated by immunohistochemistry. The selected studies are of good quality, although, any study referred to a sample size determination. Considering the lack of follow-up studies, the molecules are still potential biomarkers. Further research is required to validate these biomarkers in well-designed clinical cohort-based studies.

Cytotoxicity of the coagulant Moringa oleifera lectin (cMoL) to B16-F10 melanoma cells.

Moringa oleifera seeds are used in alternative medicine to treat inflammation, tumors and bacterial and protozoan infections, for example. The seeds contain lectins, which are carbohydrate-binding proteins with several biological properties including cytotoxicity to cancer cells. In this work, we examined the cytotoxicity of the coagulant M. oleifera lectin (cMoL) on B16-F10 murine melanoma cells. cMoL cytotoxic effects were evaluated through trypan blue assay and flow cytometry analysis. Mitochondrial superoxide levels and activation of caspases 3, 8 and 9 were measured. cMoL (1.5-16µM) reduced viability and caused cell death of B16-F10 cells with an IC50 of 9.72µM. Flow cytometry analysis indicated induction of necrosis and suggested the presence of cells in late apoptosis. Specificity for tumor cells was observed since death of normal human fibroblasts (GN) was not higher than 20% in treatments with cMoL from 1.5 to 16µM. Microscopy images revealed rounded shape and reduction of volume in B16-F10 cells treated with cMoL. cMoL increased mitochondrial ROS production and promoted caspases 3, 8 and 9 activation in B16-F10 cells, indicating the activation of apoptosis-related pathway. In conclusion, this study demonstrates that cMoL is cytotoxic to B16-F10 cells, which stimulates more investigation on the anticancer potential of this lectin.

pCramoll and rCramoll lectins induce cell death in human prostate adenocarcinoma (PC-3) cells by impairment of mitochondrial homeostasis.

Lectins from Cratylia mollis seed have shown potential in vivo antitumor actions, however the mechanism have not yet been addressed. Here we evaluated the antitumor effects of native (pCramoll) and recombinant (rCramoll) lectins from C. mollis against human prostate adenocarcinoma (PC-3) cells. The viability of PC-3 cells was analyzed with the MTT assay and ANNEXIN V/propidium iodide staining. The actions of pCramoll or rCramoll on mitochondrial superoxide production, free cytosolic calcium concentration and mitochondrial membrane potential were evaluated using fluorescent probes (MitoSox Red, Fura 2-AM and safranin O, respectively). pCramoll and rCramoll reduced the viability of PC-3 cells in a dose-dependent manner. Both lectins increased the generation of mitochondrial superoxide as well as the concentration of cytosolic calcium. These changes led to a decrease in oxidative phosphorylation, which impaired the formation of ATP. The resulting cell death was not blocked by MPT (mitochondrial permeability transition) inhibitors (Debio 025 or bongkrekic acid). Thus pCramoll and rCramoll promote PC-3 cell death through calcium signaling, leading to mitochondrial collapse. This work provides more insights into the action of pCramoll and rCramoll against cancer cells. These lectins represent valuable tools for biomedical research.