A first-in-class, first-in-human, phase I trial of CIGB-552, a synthetic peptide targeting COMMD1 to inhibit the oncogenic activity of NF-κBin patients with advanced solid tumors. Vallespi MG, Mestre B, Marrero MA, Uranga R, Rey D, Lugiollo M, et al. Int J Cancer. 2021 Sep 15;149(6):1313–21.
CIGB-552 is a synthetic peptide that interacts with COMMD1 and upregulates its protein levels. The objectives of this phase I study were safety, pharmacokinetic profile, evaluation of the lymphocytes CD4+ and CD8+ and preliminary activity in patients with advanced tumors. A 3 + 3 dose-escalation design with seven dose levels was implemented. Patients were included until a grade 3 related adverse event occurred and the maximum tolerated dose was reached. The patients received subcutaneous administration of CIGB-552 three times per week for 2 weeks. Single-dose plasma pharmacokinetics was characterized at two dose levels, and tumor responses were classified by RECIST 1.1. Twenty-four patients received CIGB-552. Dose-limiting toxicity was associated with a transient grade 3 pruritic maculopapular rash at a dose of 7.0 mg. The maximum tolerated dose was defined as 4.7 mg. Ten patients were assessable for immunological status. Seven patients had significant changes in the ratio CD4/CD8 in response to CIGB-552 treatment; three patients did not modify the immunological status. Stable disease was observed in five patients, including two metastatic soft sarcomas. We conclude that CIGB-552 at dose 4.7 mg was well tolerated with no significant adverse events and appeared to provide some clinical benefits.
Body mass-index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants. Armas Rojas NB, Lacey B, Soni M, Charles S, Carter J, Varona-Pérez P, et al. BMC Public Health. 2021 May27;21(1):963.
DOI: 10.1186/s12889-021-10911-9.
Background Cardiovascular disease accounts for about one-third of all premature deaths (ie, age < 70) in Cuba. Yet, the relevance of major risk factors, including systolic blood pressure (SBP), diabetes, and body-mass index (BMI), to cardiovascular mortality in this population remains unclear. Methods In 1996-2002, 146,556 adults were recruited from the general population in five areas of Cuba. Participants were interviewed, measured (height, weight and blood pressure) and followed up by electronic linkage to national death registries until Jan 1, 2017; in 2006-08, 24,345 participants were resurveyed. After excluding all with missing data, cardiovascular disease at recruitment, and those who died in the first 5 years, Cox regression (adjusted for age, sex, education, smoking, alcohol and, where appropriate, BMI) was used to relate cardiovascular mortality rate ratios (RRs) at ages 35-79 years to SBP, diabetes and BMI; RR were corrected for regression dilution to give associations with long-term average (ie, ‘usual’) levels of SBP and BMI. Results After exclusions, there were 125,939 participants (mean age 53 [SD12]; 55% women). Mean SBP was 124 mmHg (SD15), 5% had diabetes, and mean BMI was 24.2 kg/m2 (SD3.6); mean SBP and diabetes prevalence at recruitment were both strongly related to BMI. During follow-up, there were 4112 cardiovascular deaths (2032 ischaemic heart disease, 832 stroke, and 1248 other). Cardiovascular mortality was positively associated with SBP (>=120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88-2.18]), as did diabetes (2.15, 1.95-2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64-2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively. Conclusions This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.
Bone Mass in Young Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Espinosa-Reyes TM, Leyva González G, Domínguez Alonso E, Falhammar H. Hor Res Paediatr. 2021;94(1–2):1–8. DOI: 10.1159/000515833. Epub 2021 May 27
Background The effects of hyperandrogenism and steroid treatment on bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH) are controversial. Objectives The objectives of this study were to characterize BMD and fractures in patients with CAH and to identify whether there is an association between alterations in BMD, nutritional status, and variables related to the disease. Methods A cross-sectional descriptive study was conducted to explore clinical, hormonal, dairy consumption, physical activity, and BMD variables in patients with CAH due to 21-hydroxylase deficiency and controls matched by age, gender, skin color, body mass index, and Tanner scale. Results Fifty subjects (CAH n = 25; females n = 42 [84%]) with a mean age of 15.9 ± 5.8 years were included in the study. White skin color predominated in 34 subjects (68%), mestizo in 11 (22%), and black in 5 (10%). In patients with CAH, BMD lumbar spine was decreased compared to that in controls (0.83 ± 0.23 vs. 0.98 ± 0.26 g/cm3, p = 0.004). BMD femur was also decreased in patients with CAH; however, this was not significant (0.95 ± 0.20 vs. 1.04 ± 0.24 g/cm3, p = 0.17). There was a positive relationship between age at diagnosis, age of initiation of glucocorticoid treatment, and testosterone levels with all measurements of BMD. The daily glucocorticoid dose was negatively related to BMD. No fractures were found. Conclusions Patients with CAH had decreased BMD, especially in lumbar spine. Increased androgen exposure seemed to improve, while increased glucocorticoid dose impaired BMD.
Collaborative digital platform France-Cuba: oncorehabilitation in reproductive and sexual health. Almont T, Bujan L, Joachim C, Joguet G, Vestris M, Houpert R, et al. BMC Med Educ. 2021 Jun 9;21(1):337.
Background In the French West-Indies, few studies have been performed on fertility and sexual problems in cancer survivors, which are frequent and recurring issues reported by surveys on unmet needs. Additionally, mutualizing human and material resources and promoting cooperation through a collaborative platform are the most appropriate response to complex health pathways in the Caribbean territories. Implementation of such a collaborative platform will help to launch a strategic Caribbean partnership to transfer theoretical and technical skills and care standards in oncofertility and oncosexuality. Methods We propose to set up a collaborative digital platform to strengthen, from the French expertise, Cuban health professionals’ knowledge, know-how, and skills in oncofertility and oncosexuality. The project will be coordinated by a coordinating, scientific, and supervisory committee, and the main activities will include: 1. Theoretical training in e-learning adapted to low-speed Internet. 2. Practical training in fertility preservation and sexual rehabilitation. 3. Digital multidisciplinary consultation meetings for medical decisions to be taken for complex clinical cases. The platform will benefit from a recurrent evaluation, by the two cancer registries of Martinique and Cuba, with the following performance indicators: number of Cuban professionals trained, number of professionals sensitized, hourly volumes (or number of training courses provided), satisfaction of trained professionals, number of e-RCPs carried out online and number of missionaries supported. These indicators will be set up and analyzed by the registers. This project meets the Cuban and French health policies (cancer plans and national sexual health strategies) and will be implemented in liaison with the Health Agencies of both countries and the Embassy of France in Cuba. Discussion This project aims to provide support through bilateral exchanges to improve reproductive and sexual health in Cuba’s cancer patients. This collaboration will be based on a long-lasting French expertise and a solid Cuban health system. Consequently, this collaborative digital platform will contribute to data collection for cancer surveillance, and the two participating countries will ultimately be identified in the Caribbean as having centers of competence and excellence in oncofertility and oncosexuality with care standards.
C-Phycocyanin-derived Phycocyanobilin as a Potential Nutraceutical Approach for Major Neurodegenerative Disorders and COVID-19-induced Damage to the Nervous System. Pentón-Rol, G, Marín-Prida J, McCarty MF. Curr Neuropharmacol. 2021 Apr 8.
DOI: 10.2174/1570159X19666210408123807
The edible cyanobacterium Spirulina platensis and its chief biliprotein C-Phycocyanin have shown protective activity in animal models of diverse human health diseases, often reflecting antioxidant and anti-inflammatory effects. The beneficial effects of C-Phycocyanin seem likely to be primarily attributable to its covalently attached chromophore Phycocyanobilin (PCB). Within cells, biliverdin is generated from free heme and it is subsequently reduced to bilirubin. Although bilirubin can function as an oxidant scavenger, its potent antioxidant activity reflects its ability to inactivate some isoforms of NADPH oxidase. Free bilirubin can also function as an agonist for the aryl hydrocarbon receptor (AhR); this may explain its ability to promote protective Treg activity in cellular and rodent models of inflammatory disease. AhR agonists also promote transcription of the gene coding for Nrf-2, and hence can up-regulate phase 2 induction of antioxidant enzymes such as HO-1. Hence, it is proposed that C-Phycocyanin/PCB chiefly exert their protective effects via inhibition of NADPH oxidase activity, as well as by AhR agonism that both induces Treg activity and up-regulates phase 2 induction. This simple model may explain their potent antioxidant/anti-inflammatory effects. Additionally, PCB might mimic biliverdin in activating anti-inflammatory signaling mediated by biliverdin reductase. This essay reviews recent research in which C-Phycocyanin and/or PCB, administered orally, parenterally, or intranasally, have achieved marked protective effects in rodent and cell culture models of Ischemic Stroke and Multiple Sclerosis, and suggests that these agents may likewise be protective for Alzheimer’s disease, Parkinson’s disease, and in COVID-19 and its neurological complications.
Cuba’s contribution in the diagnosis of brain death/death by neurologic criteria. Machado C. Clin Neurol Neurosurg. 2021 Jul;206:106674. DOI: 10.1016/j.clineuro.2021.106674
I read with interest the paper by Lewis et al. to identify the countries in the Latin America/Caribbean Group of the United Nations (GRULAC) that have protocols for brain death/death by neurologic criteria (BD/DNC). Curiously, the authors don’t mention Cuba, which has been one of the most active countries in the area, since the early ’90s. The first kidney transplant in Cuba was performed on 24 February 1970, using a cadaveric donor. In September 1992, the First Symposium on Brain Death was held in Havana, with the attendance of the main and world-known authors at that time, like Cristopher Pallis, Earl Walker, among others. These conferences uninterruptedly continued over the years, and the last Symposium was held in December 2018. In the First Symposium, the Cuban Commission for Death Determination presented for the first time the Guidelines for the Determination of BD/DNC in Cuba. Since that time, Machado proposed a concept of death, based on the basic pathophysiological mechanism of consciousness generation. This author also proposed as ancillary tests in BD/DNC diagnosis the use of a test battery composed of multimodality evoked potentials (MEP) and electroretinography (ERG). Later, a Cuban Law for the determination of death was issued. The Cuban Commission The Commission stated that there is only one kind of death, based on the irreversible loss of brain functions based on the whole brain criteria. Furthermore, the Cuban law did not even mention the term ‘transplants’. It is clear the human beings die regardless bodies would be useful or not for transplantation.
Effect of Biomodulina-T® and VA-MENGOC-BC® on lymphocyte subpopulations in older adults. Hernández Ramos E, Marsán Suárez V, Casado Hernández I, Puga Gómez R, García Rivera D, Reyes Zamora MC, et al. Exp Gerontol. 2021 Jul 26;111497.
DOI: 10.1016/j.exger.2021.111497
Introduction The elderly population suffers from the natural process called immunosenescence, which may be related to the high mortality rates it has against the SARS-CoV2 virus, which is why therapies that improve the immune status are required. The combined treatment of the VA-MENGOC-BC® (V-BC) vaccine and the Biomodulina T® (BT) drug could achieve this purpose. This treatment could immunomodulate both the innate and adaptive branches of the immune system simultaneously. Objective To determine the effect of BT and V-BC on the immunomodulation of lymphocyte subpopulations in older adults. Methods Our study was carried out in 30 apparently healthy Cuban adults over 65 years of age. The study included three groups of 10 subjects per treatment: a combination of both and the monotherapies. Before and 7 days after treatment, 2 ml of peripheral blood was drawn from each subject. Multiparametric flow cytometry was used to identify lymphocyte subpopulations. For the comparison between the groups, point estimates and the confidence intervals of the Odds Ratio were made. Results We found that subpopulations of B lymphocytes and natural cytotoxic T (NKT) cells increased only with the administration of BT. Additionally, combination treatments and V-BC did not generate statistically significant immunomodulatory changes in any of the studied lymphocyte subpopulations. Conclusions BT presented an immunoenhancing effect on the B and NKT lymphocyte subpopulations of older adults. The three-dose treatment scheme a novel and specific treatment strategy for this formulation. We also were verified that the combined application of V-BC and BT did not have the expected benefits. All these findings suggest that BT administration is a promising approach for immune restoration and to offering protection in elderly patients against COVID-19.
Effect of the Addition of Alginate and/or Tetracycline on Brushite Cement Properties. Morilla C, Perdomo E, Hernández AK, Regalado R, Almirall A, Fuentes G, et al. Molecules. 2021 May 28;26(11):3272.
DOI: 10.3390/molecules26113272
Calcium phosphate cements have the advantage that they can be prepared as a paste that sets in a few minutes and can be easily adapted to the shape of the bone defect, which facilitates its clinical application. In this research, six formulations of brushite (dicalcium phosphate dihydrated) cement were obtained and the effect of the addition of sodium alginate was analyzed, such as its capacity as a tetracycline release system. The samples that contain sodium alginate set in 4 or 5 min and showed a high percentage of injectability (93%). The cements exhibit compression resistance values between 1.6 and 2.6 MPa. The drug was released in a range between 12.6 and 13.2% after 7 days. The antimicrobial activity of all the cements containing antibiotics was proven. All samples reached values of cell viability above 70 percent. We also observed that the addition of the sodium alginate and tetracycline improved the cell viability.
Evaluation of a Low-Cost Commercial Actigraph and Its Potential Use in Detecting Cultural Variations in Physical Activity and Sleep. Topalidis P, Florea C, Eigil ES, Kurapov A, Beltrán León CA, Schabus M. Sensors (Basel). 2021 May 29;21(11):3774.
DOI: 10.3390/s21113774
The purpose of the present study was to evaluate the performance of a low-cost commercial smartwatch, the Xiaomi Mi Band (MB), in extracting physical activity and sleep-related measures and show its potential use in addressing questions that require large-scale real-time data and/or intercultural data including low-income countries. We evaluated physical activity and sleep-related measures and discussed the potential application of such devices for large-scale step and sleep data acquisition. To that end, we conducted two separate studies. In Study 1, we evaluated the performance of MB by comparing it to the GT3X (ActiGraph, wGT3X-BT), a scientific actigraph used in research, as well as subjective sleep reports. In Study 2, we distributed the MB across four countries (Austria, Germany, Cuba, and Ukraine) and investigated physical activity and sleep among these countries. The results of Study 1 indicated that MB step counts correlated highly with the scientific GT3X device, but did display biases. In addition, the MB-derived wake-up and total-sleep-times showed high agreement with subjective reports, but partly deviated from GT3X predictions. Study 2 revealed similar MB step counts across countries, but significant later wake-up and bedtimes for Ukraine than the other countries. We hope that our studies will stimulate future large-scale sensor-based physical activity and sleep research studies, including various cultures.
Fungal populations in the bedroom dust of children in Havana, Cuba, and its relationship with environmental conditions. Sánchez Espinosa KC, Rojas Flores TI, Rodríguez Davydenko S, Venero Fernández SJ, Almaguer M. Environ Sci Pollut Res Int. 2021 May 22.
DOI: 10.1007/s11356-021-14231-8
The study of the fungal community composition in house dust is useful to assess the accumulative exposure to fungi in indoor environments. The objective of this research was to characterize the fungal diversity of house dust and its association with the environmental conditions of bedrooms. For this, the dust was collected from 41 bedrooms of children between the ages of 8 and 9 with a family history of asthma, residents of Havana, Cuba. The fungal content of each sample was determined by two methods: plate culture with malt extract agar and by direct microscopy. An ecological analysis was carried out from the fungal diversity detected. To describe the factors associated with the fungi detected, bivariate logistic regression was used. Through direct microscopy, between 10 and 2311 fragments of hyphae and spores corresponding mainly to Cladosporium, Coprinus, Curvularia, Aspergillus/Penicillium, Xylariaceae, and Periconia were identified. Through the culture, 0-208 CFU were quantified, where Aspergillus, Cladosporium, and Penicillium predominated. The culturability evidenced the differences between the quantification determined by both methods. A positive relationship was found between the type of cleaning of the furniture, the presence of trees in front of the bedroom, indoor relative humidity, indoor temperature, the presence of air conditioning, and natural ventilation with specific spore types and genera. The use of two different identification methods allowed to detect a greater fungal diversity in the residences evaluated. Monitoring the exposure to these fungal allergens in childhood can help to prevent sensitization in the allergic child, the development of asthma, and other respiratory diseases.
Gossypitrin, A Naturally Occurring Flavonoid, Attenuates Iron-Induced Neuronal and Mitochondrial Damage. Bécquer-Viart MA, Armentero-López A, Álvarez-Almiñaque D, Fernández-Acosta R, Matos-Peralta Y, D’Vries RF, et al. Molecules. 2021 Jun 2;26(11):3364.
The disruption of iron homeostasis is an important factor in the loss of mitochondrial function in neural cells, leading to neurodegeneration. Here, we assessed the protective action of gossypitrin (Gos), a naturally occurring flavonoid, on iron-induced neuronal cell damage using mouse hippocampal HT-22 cells and mitochondria isolated from rat brains. Gos was able to rescue HT22 cells from the damage induced by 100 µM Fe(II)-citrate (EC50 8.6 µM). This protection was linked to the prevention of both iron-induced mitochondrial membrane potential dissipation and ATP depletion. In isolated mitochondria, Gos (50 µM) elicited an almost complete protection against iron-induced mitochondrial swelling, the loss of mitochondrial transmembrane potential and ATP depletion. Gos also prevented Fe(II)-citrate-induced mitochondrial lipid peroxidation with an IC50 value (12.45 µM) that was about nine time lower than that for the tert-butylhydroperoxide-induced oxidation. Furthermore, the flavonoid was effective in inhibiting the degradation of both 15 and 1.5 mM 2-deoxyribose. It also decreased Fe(II) concentration with time, while increasing O2 consumption rate, and impairing the reduction of Fe(III) by ascorbate. Gos-Fe(II) complexes were detected by UV-VIS and IR spectroscopies, with an apparent Gos-iron stoichiometry of 2:1. Results suggest that Gos does not generally act as a classical antioxidant, but it directly affects iron, by maintaining it in its ferric form after stimulating Fe(II) oxidation. Metal ions would therefore be unable to participate in a Fenton-type reaction and the lipid peroxidation propagation phase. Hence, Gos could be used to treat neuronal diseases associated with iron-induced oxidative stress and mitochondrial damage.
Impact of smoking on COVID-19 outcomes: a HOPE Registry subanalysis. Espejo-Paeres C, Núñez-Gil IJ, Estrada V, Fernández-Pérez C, Uribe-Heredia G, Cabré-Verdiell C, et al. BMJ Nutr Prev Health. 2021 Jun 17;4(1):285–92.
Background Smoking has been associated with poore outcomes in relation to COVID-19. Smokers have higher risk of mortality and have a more severe clinical course. There is paucity of data available on this issue, and a definitive link between smoking and COVID-19 prognosis has yet to be established. Methods We included 5224 patients with COVID-19 with an available smoking history in a multicentre international registry Health Outcome Predictive Evaluation for COVID-19 (NCT04334291). Patients were included following an in-hospital admission with a COVID-19 diagnosis. We analysed the outcomes of patients with a current or prior history of smoking compared with the non-smoking group. The primary endpoint was all-cause in-hospital death. Results Finally, 5224 patients with COVID-19 with available smoking status were analysed. A total of 3983 (67.9%) patients were non-smokers, 934 (15.9%) were former smokers and 307 (5.2%) were active smokers. The median age was 66 years (IQR 52.0-77.0) and 58.6% were male. The most frequent comorbidities were hypertension (48.5%) and dyslipidaemia (33.0%). A relevant lung disease was present in 19.4%. In-hospital complications such sepsis (23.6%) and embolic events (4.3%) occurred more frequently in the smoker group (p<0.001 for both). All cause-death was higher among smokers (active or former smokers) compared with non-smokers (27.6 vs 18.4%, p<0.001). Following a multivariate analysis, current smoking was considered as an independent predictor of mortality (OR 1.77, 95% CI 1.11 to 2.82, p=0.017) and a combined endpoint of severe disease (OR 1.68, 95% CI 1.16 to 2.43, p=0.006). Conclusion Smoking has a negative prognostic impact on patients hospitalised with COVID-19.
Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy with Pegylated Interferon-Alpha. Marques Vieira da Silva A, Alvarado-Arnez LE, Azamor T, Batista-Silva LR, Leal-Calvo T, de Lima Bezerra OC, et al. Front Cell Infect Microbiol. 2021 Jul 7;11:656393.
DOI: 10.3389/fcimb.2021.656393
Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors’ genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).
Molecular aspects concerning the use of SARS-CoV-2 receptor binding domain as a target for preventive vaccines. Valdés-Balbing Y, Santana-Mederos D, Paquet F, Fernández S, Climent Y, Chiodo F, et al. ACS Cent Sci. 2021 May 26;7(5):757–67.
The development of recombinant COVID-19 vaccines has resulted from scientific progress made at an unprecedented speed during 2020. The recombinant spike glycoprotein monomer, its trimer, and its recombinant receptor-binding domain (RBD) induce a potent anti-RBD neutralizing antibody response in animals. In COVID-19 convalescent sera, there is a good correlation between the antibody response and potent neutralization. In this review, we summarize with a critical view the molecular aspects associated with the interaction of SARS-CoV-2 RBD with its receptor in human cells, the angiotensin-converting enzyme 2 (ACE2), the epitopes involved in the neutralizing activity, and the impact of virus mutations thereof. Recent trends in RBD-based vaccines are analyzed, providing detailed insights into the role of antigen display and multivalence in the immune response of vaccines under development.
Nutraceutical and therapeutic potential of Phycocyanobilin for treating Alzheimer’s disease. Matamoros BP, Prida JM, Rol GP. J Biosci. 2021;46:42.
Alzheimer’s disease (AD) is a devastating neurodegenerative condition provoking the loss of cognitive and memory performances. Despite huge efforts to develop effective AD therapies, there is still no cure for this neurological condition. Here, we review the main biological properties of Phycocyanobilin (PCB), accounting for its potential uses against AD. PCB, given individually or released in vivo from C-Phycocyanin (C-PC), acts as a bioactive-molecule-mediating antioxidant, is anti-inflammatory and has immunomodulatory activities. PCB/C-PC are able to scavenge reactive oxygen and nitrogen species, to counteract lipid peroxidation and to inhibit enzymes such as NADPH oxidase and COX-2. In animal models of multiple sclerosis and ischemic stroke, these compounds induce remyelination as demonstrated by electron microscopy and the expression of genes such as Mal up-regulation of and Lingo-1 down-regulation. These treatments also reduce pro-inflammatory cytokines levels and induce immune suppressive genes. PCB/C-PC protects isolated rat brain mitochondria and inactivate microglia, astrocytes and neuronal apoptosis mediators. Such processes are all involved in the pathogenic cascade of AD, and thus PCB may effectively mitigate the injury in this condition. Furthermore, PCB can be administered safely by oral or parenteral routes and therefore, could be commercially offered as a nutraceutical supplement or as a pharmaceutical drug.
Scalable Bio Marker Combinations for Early Stroke Diagnosis: A Systematic Review. de la Caridad Baez S, García Del Barco D, Hardy-Sosa A, Guillén Nieto G, Bringas-Vegas ML, Llibre-Guerra JJ, et al. Frongt Neurol. 2021 May 28;12:638693.
DOI: 10.3389/fneur.2021.638693
Background Acute stroke treatment is a time-critical process in which every minute counts. Laboratory biomarkers are needed to aid clinical decisions in the diagnosis. Although imaging is critical for this process, these biomarkers may provide additional information to distinguish actual stroke from its mimics and monitor patient condition and the effect of potential neuroprotective strategies. For such biomarkers to be effectively scalable to public health in any economic setting, these must be cost-effective and non-invasive. We hypothesized that blood-based combinations (panels) of proteins might be the key to this approach and explored this possibility through a systematic review. Methods We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines for systematic review. Initially, the broader search for biomarkers for early stroke diagnosis yielded 704 hits, and five were added manually. We then narrowed the search to combinations (panels) of the protein markers obtained from the blood. Results Twelve articles dealing with blood-based panels of protein biomarkers for stroke were included in the systematic review. We observed that NR2 peptide (antibody against the NR2 fragment) and glial fibrillary acidic protein (GFAP) are brain-specific markers related to stroke. Von Willebrand factor (vWF), matrix metalloproteinase 9 (MMP-9), and S100β have been widely used as biomarkers, whereas others such as the ischemia-modified albumin (IMA) index, antithrombin III (AT-III), and fibrinogen have not been evaluated in combination. We herein propose the following new combination of biomarkers for future validation: panel 1 (NR2 + GFAP + MMP-9 + vWF + S100β), panel 2 (NR2 + GFAP + MMP-9 + vWF + IMA index), and panel 3 (NR2 + GFAP + AT-III + fibrinogen). Conclusions More research is needed to validate, identify, and introduce these panels of biomarkers into medical practice for stroke recurrence and diagnosis in a scalable manner. The evidence indicates that the most promising approach is to combine different blood-based proteins to provide diagnostic precision for health interventions. Through our systematic review, we suggest three novel biomarker panels based on the results in the literature and an interpretation based on stroke pathophysiology.
Synthesis and Evaluation of AlgNa-g-Poly(QCL-co-HEMA) Hydrogels as Platform for Chondrocyte Proliferation and Controlled Release of Betamethasone. García-Cource J, Vernhes M, Bada N, Agüero L, Valdés O, Álvarez-Barreto J, et al. Int J Mol Sci. 2021 May 27;22(11):5730. DOI: 10.3390/ijms22115730
Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.
Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300. Rosales M, Pérez GV, Ramón AC, Cruz Y, Rodríguez-Ulloa A, Besada V, et al. Biomedicines. 2021 Jul 1;9(7).
Protein kinase CK2 has emerged as an attractive therapeutic target in acute myeloid leukemia (AML), an advent that becomes particularly relevant since the treatment of this hematological neoplasia remains challenging. Here we explored for the first time the effect of the clinical-grade peptide-based CK2 inhibitor CIGB-300 on AML cells proliferation and viability. CIGB-300 internalization and subcellular distribution were also studied, and the role of B23/nucleophosmin 1 (NPM1), a major target for the peptide in solid tumors, was addressed by knock-down in model cell lines. Finally, pull-down experiments and phosphoproteomic analysis were performed to study CIGB-interacting proteins and identify the array of CK2 substrates differentially modulated after treatment with the peptide. Importantly, CIGB-300 elicited a potent anti-proliferative and proapoptotic effect in AML cells, with more than 80% of peptide transduced cells within three minutes. Unlike solid tumor cells, NPM1 did not appear to be a major target for CIGB-300 in AML cells. However, in vivo pull-down experiments and phosphoproteomic analysis evidenced that CIGB-300 targeted the CK2α catalytic subunit, different ribosomal proteins, and inhibited the phosphorylation of a common CK2 substrates array among both AML backgrounds. Remarkably, our results not only provide cellular and molecular insights unveiling the complexity of the CIGB-300 anti-leukemic effect in AML cells but also reinforce the rationale behind the pharmacologic blockade of protein kinase CK2 for AML-targeted therapy.
The paradox of haematopoietic cell transplant in Latin America. Jaimovich G, Gale RP, Hanesman I, Vázquez A, Hammerschlack N, Pinto Simoes B, et al. Bone Marrow Transplant. 2021 May 13. DOI: 10.1038/s41409-021-01321-x
Hematopoietic cells transplants are technically complex and expensive imposing a huge burden on health care systems, especially those in developing countries and regions. In 2017 > 4500 transplants were done in 13 Latin American countries with established transplant programmes. We interrogated data on transplant rate, cost, funding source, hospital type, Gini coefficient and the United Nations Development Programme Inequality-Adjusted Human Development Index to determine co-variates associated with transplant development. Transplant rates varied almost 30-fold between the 13 countries from 345 in Uruguay to 12 in Venezuela with a regional transplant rate 7-8-fold lower compared with the US and EU. We found significant correlations between higher transplant cost, public funding, transplants in private hospitals with transplant rate. Low cost per transplant regardless of payor and transplants done in public hospitals were associated with low transplant rates. In contrast, high cost per transplant funded by the government and transplants done in private hospitals were associated with high transplant rates. Surprisingly, we found transplant rates were higher when transplants cost more, when they were done in private for-profit hospitals and payed for with public funds. These data give insights how to increase transplant rates in Latin America and other developing regions.
The Health Equity Network of the Americas: inclusion, commitment, and action. Castro A, Sáenz R, Avellaneda X, Cáceres C, Galvão L, Mas Bermejo P, et al. Rev Panam Salud Pública. 2021 Jul 1;45:e79. DOI: 10.26633/RPSP.2021.79. Spanish, English.
The Health Equity Network of the Americas (HENA) is a multidisciplinary network that promotes knowledge sharing and intersectoral action for equity in health and human rights in the Americas. The objectives of HENA are: 1) to share successful experiences in the development of interventions, considering the social determinants and determination of health, to achieve participatory and community-based health responses; 2) to analyze the health, social, political, environmental and economic impacts of the COVID-19 pandemic; 3) to identify the effects of pandemic care on populations most at risk because of their age and pre-existing health conditions; 4) examine the situation at borders and population movements in the spread of the pandemic and its effects on migrant populations; 5) propose strategies to ensure access to comprehensive care for pregnant women in order to reduce maternal and neonatal suffering, morbidity, and mortality; and 6) analyze violations of human rights and the right to health of historically marginalized populations, including street dwellers and other communities that depend on public spaces and the street for survival. The analytical and intervention models for health equity at HENA are based on various approaches, including social medicine, social epidemiology, medical anthropology, human ecology, and One Health.
The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer. Crombet Ramos T, Santos Morales O, Dy GK, León Monzón K, Lage Dávila A. Front Oncol. 2021 Jun 15;11:639745. DOI: 10.3389/fonc.2021.639745
Advanced non-small cell lung cancer (NSCLC) has faced a therapeutic revolution with the advent of tyrosine kinase inhibitors (TKIs) and immune checkpoints inhibitors (ICIs) approved for first and subsequent therapies. CIMAvax-EGF is a chemical conjugate between human-recombinant EGF and P64, a recombinant protein from Neisseria meningitides, which induces neutralizing antibodies against EGF. In the last 15 years, it has been extensively evaluated in advanced NSCLC patients. CIMAvax-EGF is safe, even after extended use, and able to keep EGF serum concentration below detectable levels. In a randomized phase III study, CIMAvax-EGF increased median overall survival of advanced NSCLC patients with at least stable disease after front-line chemotherapy. Patients bearing squamous-cell or adenocarcinomas and serum EGF concentration above 870 pg/ml had better survival compared to control patients treated with best supportive care as maintenance, confirming tumors’ sensitivity to the EGF depletion. This manuscript reviews the state-of-the-art NSCLC therapy and proposes the most promising scenarios for evaluating CIMAvax-EGF, particularly in combination with TKIs or ICIs. We hypothesize that the optimal combination of CIMAvax-EGF with established therapies can further contribute to transform advanced cancer into a manageable chronic disease, compatible with years of good quality of life.
Why We Are Losing the War Against COVID-19 on the Data Front and How to Reverse the Situation. Prieto Merino D, Da Providencia E Costa RB, Bacallao Gallestey J, Sofat R, Chung SC, Potts H. JMIRx Med. 2021 May 5;2(2):e20617. DOI: 10.2196/20617
With over 117 million COVID-19-positive cases declared and the death count approaching 3 million, we would expect that the highly digitalized health systems of high-income countries would have collected, processed, and analyzed large quantities of clinical data from patients with COVID-19. Those data should have served to answer important clinical questions such as: what are the risk factors for becoming infected? What are good clinical variables to predict prognosis? What kinds of patients are more likely to survive mechanical ventilation? Are there clinical subphenotypes of the disease? All these, and many more, are crucial questions to improve our clinical strategies against the epidemic and save as many lives as possible. One might assume that in the era of big data and machine learning, there would be an army of scientists crunching petabytes of clinical data to answer these questions. However, nothing could be further from the truth. Our health systems have proven to be completely unprepared to generate, in a timely manner, a flow of clinical data that could feed these analyses. Despite gigabytes of data being generated every day, the vast quantity is locked in secure hospital data servers and is not being made available for analysis. Routinely collected clinical data are, by and large, regarded as a tool to inform decisions about individual patients, and not as a key resource to answer clinical questions through statistical analysis. The initiatives to extract COVID-19 clinical data are often promoted by private groups of individuals and not by health systems, and are uncoordinated and inefficient. The consequence is that we have more clinical data on COVID-19 than on any other epidemic in history, but we have failed to analyze this information quickly enough to make a difference. In this viewpoint, we expose this situation and suggest concrete ideas that health systems could implement to dynamically analyze their routine clinical data, becoming learning health systems and reversing the current situation.
