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Analysis of High Molecular Mass Compounds from the Spider Pamphobeteus verdolaga Venom Gland. A Transcriptomic and MS ID Approach
(Universidad cooperativa de Colombia, sede Medellín, Medicina, 2021-06-29) Sebastian Estrada-Gómez, Leidy Johana Vargas-Muñoz; Cesar Segura Latorre, Monica Maria Saldarriaga-Cordoba; Claudia Marcela Arenas-Gómez
Nowadays, spider venom research focuses on the neurotoxic activity of small peptides. In this study, we investigated high-molecular-mass compounds that have either enzymatic activity or housekeeping functions present in either the venom gland or venom of Pamphobeteus verdolaga. We used proteomic and transcriptomic-assisted approaches to recognize the proteins sequences related to high-molecular-mass compounds present in either venom gland or venom. We report the amino acid sequences (partial or complete) of 45 high-molecular-mass compounds detected by transcriptomics showing similarity to other proteins with either enzymatic activity (i.e., phospholipases A2 , kunitz-type, hyaluronidases, and sphingomyelinase D) or housekeeping functions involved in the signaling process, glucanotransferase function, and beta-N-acetylglucosaminidase activity. MS/MS analysis showed fragments exhibiting a resemblance similarity with different sequences detected by transcriptomics corresponding to sphingomyelinase D, hyaluronidase, lycotoxins, cysteine-rich secretory proteins, and kunitz-type serine protease inhibitors, among others. Additionally, we report a probably new protein sequence corresponding to the lycotoxin family detected by transcriptomics. The phylogeny analysis suggested that P. verdolaga includes a basal protein that underwent a duplication event that gave origin to the lycotoxin proteins reported for Lycosa sp. This approach allows proposing an evolutionary relationship of high-molecular-mass proteins among P. verdolaga and other spider species.
Assessing the reporting of Dengue, Chikungunya and Zika to the National Surveillance System in Colombia from 2014–2017: A Capture-recapture analysis accounting for misclassification of arboviral diagnostics
(Faculty of Medicine, Universidad Cooperativa de Colombia, Villavicencio, Colombia,, 2021-02-04) Carabali, Mabel; Jaramillo-Ramirez, Gloria I; Rivera, Vivian; Mina, Neila-Julieth; Restrepo, Berta; Zinszer, Kate
Background. Chikungunya, dengue, and Zika are three different arboviruses which have similar symp- toms and are a major public health issue in Colombia. Despite the mandatory reporting of these arboviruses to the National Surveillance System in Colombia (SIVIGILA), it has been reported that the system captures less than 10% of diagnosed cases in some cities. Methodology/Principal findings. To assess the scope and degree of arboviruses reporting in Colombia between 2014–2017, we conducted an observational study of surveillance data using the capture-recapture approach in three Colombian cities. Using healthcare facility registries (capture data) and surveillance-notified cases (recapture data), we estimated the degree of reporting by clinical diagnosis. We fit robust Poisson regressions to identify predictors of reporting and estimated the predicted probability of reporting by disease and year. To account for the potential mis- classification of the clinical diagnosis, we used the simulation extrapolation for misclassifica- tion (MC-SIMEX) method. A total of 266,549 registries were examined. Overall arboviruses’ reporting ranged from 5.3% to 14.7% and varied in magnitude according to age and year of diagnosis. Dengue was the most notified disease (21–70%) followed by Zika (6–45%). The highest reporting rate was seen in 2016, an epidemic year. The MC-SIMEX corrected rates indicated underestimation of the reporting due to the potential misclassification bias. Conclusions. These findings reflect challenges on arboviruses’ reporting, and therefore, potential chal- lenges on the estimation of arboviral burden in Colombia and other endemic settings with similar surveillance systems.
Atorvastatin Effectively Inhibits Ancestral and Two Emerging Variants of SARS-CoV-2 in vitro
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000, 2022-03-18) Hernández, Juan Carlos; Zapata-Cardona, María I; Flórez-Álvarez, Lizdany; Hernández, Juan Carlos; Zapata-Builes, Will; Guerra-Sandoval, Ariadna L; Hincapié-García, Jaime; Rugeles, Maria T
This article evaluated the in vitro antiviral effect of atorvastatin (ATV) against SARS-CoV-2 and identified the interaction affinity between this compound and two SARS-CoV-2 proteins. The antiviral activity of atorvastatin against this virus was evaluated by three different treatment strategies [(i) pre-post treatment, (ii) pre-infection treatment, and (iii) post-infection treatment] using Vero E6 and Caco-2 cells. The interaction of atorvastatin with RdRp (RNA-dependent RNA polymerase) and 3CL protease (3-chymotrypsin-like protease) was evaluated by molecular docking. The CC50s (half-maximal cytotoxic concentrations) obtained for ATV were 50.3 and 64.5 μM in Vero E6 and Caco-2, respectively. This compound showed antiviral activity against SARS-CoV-2 D614G strain in Vero E6 with median effective concentrations (EC50s) of 15.4, 12.1, and 11.1μM by pre-post, pre-infection, and post-infection treatments, respectively. ATV also inhibited Delta and Mu variants by pre-post treatment (EC50s of 16.8 and 21.1μM, respectively). In addition, ATV showed an antiviral effect against the D614G strain independent of the cell line (EC50 of 7.4μM in Caco-2). The interaction of atorvastatin with SARS-CoV-2 RdRp and 3CL protease yielded a binding affinity of −6.7kcal/mol and −7.5kcal/mol, respectively. Our study demonstrated the in vitro antiviral activity of atorvastatin against the ancestral SARS-CoV-2 D614G strain and two emerging variants (Delta and Mu), with an independent effect of the cell line. A favorable binding affinity between ATV and viral proteins by bioinformatics methods was found. Due to the extensive clinical experience of atorvastatin use, it could prove valuable in the treatment of COVID-19.
Calcitriol decreases HIV-1 transfer in vitro from monocyte-derived dendritic cells to CD4 + T cells, and downregulates the expression of DC-SIGN and SIGLEC-1
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000, 2021-09-09) Álvarez, Natalia; Gonzalez, Sandra M; Hernández, Juan Carlos; Rugeles, Maria T; Aguilar-Jimenez, Wbeimar
Characterization of a Lab-Scale Process to Produce Whole IgG Antivenom Covering Scorpion Stings by Genus Tityus and Centruroides of Colombia
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina, Medellín y Envigado, 2022-08-25) Vargas -Muñoz, Leidy johana; Estrada-Gómez, Sebastian; Núñez, Vitelbina; Vargas-Muñoz, Leidy Johana; Madrid-Bracamonte, Carlos A.; Preciado, Lina Maria; Estrada Gomez, Sebastian
Scorpion stings are a public health event in Colombia lacking official epidemiological data, and are considered a medical emergency. Despite the two local producers of antivenoms, neither of them is currently manufacturing scorpion antivenoms. We present the characterization of a lab-scale process to produce the first specific scorpion antivenom for Colombia, formulated to cover scorpion stings produced by Tityus pachyurus, Tityus asthenes, Tityus fuhrmanii, Centruroides spp. To do so, rabbits were immunized by subcutaneous injection with each venom using an immunization program of 3 months. After each rabbit reached the required IgG concentration, rabbits were bled, and plasma was separated by decantation under refrigeration. Immunoglobulins were purified from each hyperimmune plasma using a methodology including precipitation with ammonium sulfate, thermocoagulation, and purification through an ultrafiltration process using a ready-to-use and reusable laboratory crossflow tangential cassette with a polyethersulfone membrane. Each hyperimmune plasma was processed by being separated and freeze-dried at the end of the process. Rabbits were able to produce specific IgG antibodies recognizing the respective immunization venom; even an in vitro interspecies cross-recognition was detected. The separation and purification processes allowed us to obtain IgG products without considerable contaminants (except for albumin). The process was characterized, and critical stages were identified
Comparison among plaque assay, tissue culture infectious dose (TCID ) and real-time RT-PCR for SARS-CoV-2 variants quantification
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000, 2022-06) Hernández, Juan Carlos; Zapata-Cardona, Isabel; Flórez-Álvarez, Lizdany; Gómez-Gallego, Diana Maryory; Moncada-Díaz, Maria Juliana; Hernandez, Juan Carlos; Díaz, Francisco; Rugeles, Maria Teresa; Aguilar-Jiménez, Wbeimar; Zapata, Wildeman
Background and Objectives: SARS-CoV-2 variants of concern (VOC) and interest (VOI) pose a significant threat to public health because the rapid change in the SARS-CoV-2 genome can alter viral phenotypes such as virulence, transmissibility and the ability to evade the host response. Hence, SARS-CoV-2 quantification techniques are essential for timely diagnosis and follow-up. Besides, they are vital to understanding viral pathogenesis, antiviral evaluation, and vaccine development. Materials and Methods: Five isolates of SARS-CoV-2: D614G strain (B.1), three VOC (Alpha, Gamma and Delta), and one VOI (Mu) were used to compare three techniques for viral quantification, plaque assay, median tissue culture infectious dose (TCID ) and real-time RT-PCR. Results: Plaque assay showed viral titers between 0.15 ± 0.01×107 and 1.95 ± 0.09×107 PFU/mL while viral titer by TCID assay was between 0.71 ± 0.01×106 to 4.94 ± 0.80×106 TCID /mL for the five SARS-CoV-2 isolates. The PFU/mL titer obtained by plaque and the calculated from TCID assays differed by 0.61 log10, 0.59 log10, 0.59 log10 and 0.96 log10 for Alfa, Gamma, Delta, and Mu variants (p≤0.0007), respectively. No differences were observed for the D614G strain. Real-time PCR assay exhibited titers ranging from 0.39 ± 0.001×108 to 3.38 ± 0.04×108 RNA copies/µL for all variants. The relation between PFU/mL and RNA copies/mL was 1:29800 for D614G strain, 1:11700 for Alpha, 1:8930 for Gamma, 1:12500 for Delta, and 1:2950 for Mu. Conclusion: TCID assay was comparable to plaque assay for D614G but not for others SARS-CoV-2 variants. Our data demonstrated a correlation among PFU/mL and E gene RNA copies/µL, units of measure commonly used to quantify the viral load in diagnostic and research fields. The results suggest that the proportion of infectious virions in vitro changes depending on the SARS-CoV-2 variant, being Mu, the variant reaching a higher viral titer with fewer viral copies.
Efectos adversos de la exposición prenatal al material particulado del aire sobre el feto y el recién nacido
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina, Medellín y Envigado, 2022-05-09) Gómez, Diana M.; Hernandez, Juan C.; Mendivil, Jose A.
Particulate matter (PM) is a group of solid and liquid elements produced by different anthropogenic and natural activities, which are emitted directly into the air. It has different physicochemical and thermodynamic properties and according to its aerodynamic diameter, it can be classified asPM10 (<10 μm), PM2.5 (<2.5 μm) and PM0.1 (<0.1 μm). It can be inhaled and reach other organs from the lungs, causing respiratory, cardiovascular and neurological diseases, among others. Considering that the foetus is susceptible to air pollutants such as PM through gestational exposure and that early life disturbances are crucial for development, PM can cause various disorders or complications, including premature birth, low birth weight and neuropsychological damage, among others. This review summarizes the epidemiological evidence that demonstrates the relationship between maternal exposure to PM and adverse outcomes in foetal development, birth, and childhood, as well as some molecular mechanisms that could explain these associations.
Efectos del material particulado sobre las células endoteliales, epiteliales y del sistema inmune
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000, 2022-02-15) Hernández, Juan Carlos; Cano-Granada, Danna; Ramírez-Ramírez, Mariana; Gómez, Diana M; Hernández, Juan carlos
Estimación de la frecuencia de infección por Helicobacter pylori en pacientes con lesiones potencialmente malignas gástricas del municipio de Pasto-Nariño, 2016-2019.
(Grupo interdisciplinario de investigación en Salud - Enfermedad (GIISE). Facultad de Medicina. Universidad Cooperativa de Colombia, Pasto, Colombia, 2022-03) Mejia-Ortiz, L; Rosero-Galindo, CY; Carlosama-Rosero, YH; Castillo-Giraldo, A
Aim: To estimate the frequency of Helicobacter pylori infection in potentially malignant stomach lesions in patients of the city of Pasto- Nariño. Materials and methods: Retrospective study with secondary analysis of sociodemographic and histopathological information derived from pathology reports for gastric biopsies of patients from the department of Nariño, Colombia from year 2016-2019. Results: Patients from the city of Pasto (n=359) presented a percentage of detection for Helicobacter pylori of 35.6% and the infection was significantly higher in men than in women (p=0.037). The average age of men positive for Helicobacter pylori was 44 years and women 47 years (p<0.001). The average age of the cases of chronic atrophic gastritis in men and women was 49 and 54 years respectively (p<0.001) and for intestinal metaplasia cases, the average age was 59 years in men and 61 years in women (p<0.001). Conclusions: In the present study, the detection of Helicobacter pylori was higher in the male group compared to the female group (43.2% vs 31.6% respectively). The frequency of atrophic chronic gastritis and intestinal metaplasia in men was 37.9% and 23.1% respectively; in women was 35.2% and 15.1% respectively
Excess all-cause mortality and COVID-19-related mortality: a temporal analysis in 22 countries, from January until August 2020
(Faculty of Medicine, Universidad Cooperativa de Colombia, Villavicencio, Colombia,, 2022-02) Achilleos, Souzana; Annalisa, Quattrochi; Gabel, Jhon; Heraclides, Alexandros; Jaramillo Ramirez, Gloria Isabel; Martin Garzon, Oscar Dario; Mortensen, Laust; Critchley, Julia
Background: This study aimed to investigate overall and sex-specific excess all-cause mor- tality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. Methods: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015–2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015–2019 average and (ii) difference between observed and expected 2020 deaths. Results: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. Conclusions: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may ex- plain the observed variability in mortality changes.
Expresión de los componentes del inflamasoma y su relación con los marcadores de riesgo cardiovascular en personas con infección por HIV-1
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000, 2022-04-08) Hernández, Juan Carlos; León, Kevin; Marín-Palma, Damariz; Gallego, Salomón; Yepes, Cristina; Vélez, Jhonatan; Castro, Gustavo A.; Jaimes, Fabián; Taborda, Natalia; Rugeles, María Teresa; Hernández, Juan C.
Humoral Response to BNT162b2 Vaccine Against SARS-CoV-2 Variants Decays After Six Months
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000, 2022-05-02) Hernandez, Juan Carlos; Lopera, Tulio J.; Chvatal-Medina, Mateo; Flórez-Álvarez, Lizdany; Zapata-Cardona, Maria I.; Taborda, Natalia A.; Rugeles, Maria T.; Hernandez, Juan C.
Ivermectin in COVID-19. Argumentun ad ignorantiam?
(Grupo Interdisciplinario de Investigaciòn Salud-Enfermedad. Universidad Cooperativa de Colombia, 2020-10-01T00:00:00Z) Carlosama-Rosero, Y; Carlosama-Rosero, Yeison
Miocardiopatía de Takotsubo en paciente masculino joven. Reporte de caso.
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina, Medellín y Envigado, 2022-09-27) Velásquez Restrepo, Rafael Santiago; Botero Franco, María Paula; Henao Pérez, Marcela; López Medina, Diana Carolina
The case of a 27-year-old male patient is described, who was referred to a highly complex hospital after an acute myocardial infarction (AMI) was suspected. After performing an angiography, a significant involvement of any vascular territory was ruled out, which led to the diagnosis of Takotsubo Syndrome (TTS). This disease is more prevalent in postmenopausal women. Although it is reported to a lesser extent in men, it has been seen that in them, there is a higher rate of complications, mainly when it occurs in young patients. In turn, the diagnosis in this population is usually delayed due to its severe forms of presentation and the little suspicion that exists precisely because of the limited data currently provided by epidemiology
Molecular detection of Leptospira in synanthropic and wild rodents from Villavicencio municipality, Colombia
(Universidad Cooperativa de Colombia, 2022-09-19) Sánchez Lerma, Liliana; Rojas Gulloso, Andres Camilo; Mattar, Salim; Cogollo, Veronica
Introduction: Rodents are potential transmitters of Leptospira spp. In the municipality of Villavicencio, Colombia, leptospirosis is a disease that, although notifiable, is still underreported. In this region, rodent species that can host pathogenic leptospira remain unknown. Objective: To detect the presence of Leptospira spp. through molecular analysis in rodents (Rodentia) from peri-urban and rural areas belonging to the municipality of Villavicencio in Colombia. Methods: Peri-urban and rural areas of the townships belonging to Villavicencio municipality were selected for sampling. These areas presented similar ecological conditions: they were near water bodies and peridomiciliary areas, and some of them included fields of agricultural crops. Rodents´ kidneys were removed and frozen in liquid nitrogen. DNA was extracted using a commercial kit and subsequently amplified through conventional polymerase chain reaction.Results: The rodent species collected were: Rattus rattus, Mus musculus, Zygodontomys brevicauda, Oligoryzomys sp, Hylaeamys (formerly Oryzomys) and Proechimys cf. oconnelli. Leptospira DNA was amplified in six rodents and the purified amplicons were sent to Macrogen Inc. (Seoul, Korea) for sequencing. The alignment analysis of the sequenced products demonstrated 98.64% of coverage and identity with Leptospira interrogans. Conclusions: This is the first study carried out on wild and synanthropic rodents in the municipality of Villavicencio. The incidence of leptospirosis raises the alarm due to the important role of these small mammals in the transmission of this zoonosis, which is considered the second cause, after dengue, of undifferentiated febrile illness in Villavicencio.
Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000, 2022-05-09) Hernandez, Juan Carlos; Valderrama, Andrés; Ortiz‑Hernández, Paul; Agraz‑Cibrián, Juan Manuel; Tabares‑Guevara, Jorge H.; Gómez, Diana M.; Zambrano‑Zaragoza, José Francisco; Taborda, NataliaA.; Hernandez, Juan C.
Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January–August 2020
(Faculty of Medicine, Universidad Cooperativa de Colombia, Villavicencio, Colombia,, 2022) Pagola Ugarte, Maider; Achilleos, Souzana; Quatrochi, Annalisa; Gabel, Jhon; Pinilla, Maria Angelica; Jaramillo, Gloria Isabel
Background: Understanding the impact of the burden of COVID‐19 is key to successfully navigating the COVID‐19 pandemic. As part of a larger investigation on COVID‐19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). Methods: Age‐ and sex‐specific COVID‐19 death numbers from primary national sources were collected by an inter‐ national research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. Results: As of August 2020, 442,677 (range: 18–185,083) deaths attributed to COVID‐19 were recorded in 17 coun‐ tries which translated to 4,210,654 (range: 112–1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. Conclusions: Our results highlight the role of PYLL as a tool to understand the impact of COVID‐19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pan‐ demic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID‐19 in terms of premature mortality.
Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2
(Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000, 2021-10-11) Hernández, Juan Carlos; Castillo, Jorge Andrés; Giraldo, Diana M; Hernández, Juan Carlos; M. Smit, Jolanda; Rodenhuis-Zybert, Izabela A.; Urcuqui-Inchima, Silvio
Reproducibility of rapid diagnostic tests for Trypanosoma cruzi infection in endemic areas of Colombia
(Universidad Cooperativa de Colombia, 2021-12-16) Sánchez Lerma, Liliana; Rojas Gulloso, Andres Camilo; Montenegro Lopez, Diego; Fragozo, Pedro; Universidad Cooperativa de Colombia
Introduction: Chagas disease is a neglected tropical disease of interest to public health because of its social and economic burden. Identifying infected and sick people with Chagas disease constitutes the first step towards achieving World Health Ooganization’s goals for 2020. Objective: To evaluate the reproducibility with gold standard of a rapid diagnostic test for detection of antibodies to T. cruzi; and to propose a diagnostic algorithm for Chagas disease under the point-of-care concept in an area with limited access to health care coverage. Material and Methods: A cross-sectional study was performed to detect antibodies to T. cruzi in 151 indigenous volunteers belonging to three ethnic groups of the Sierra Nevada de Santa Marta, Colombia. Rapid tests-PDR SD BIOLINE Chagas Ab were implemented in the field versus confirmation in the laboratory using two standardized serological methods (ELISAs). Results: The results show that 19,2 % seroreactivity for T. cruzi was found among the entire population screening. The highest rate of human infection with T. cruzi was detected in the Wiwa community. No significant differences between rapid diagnostic test and the standard techniques (ELISAs) were found. Sensitivity, specificity and concordance for RDT were 100 % (Kappa: 1,0). Conclusions: The Sierra Nevada de Santa Marta continues to be a hyperendemic area for Chagas disease. The area is difficult to access and has low or no primary health care coverage, making the assessed rapid diagnostic test a useful tool for screening programs and defining treatment and control plans, which represents the first approach at establishing a point-ofcare testing strategy for endemic countries for Chagas disease.
Sequential development of embryoblast-like memory entities in human cancer tissues: an evolutionary self-repair structure with pluripotentiality
(Universidad Cooperativa de Colombia, 2022-09-14) Sánchez Lerma, Liliana; Diaz Torres, Jairo; Diaz Torres, Luis
Hidden collective organization of cancer cells can partially or completely return to embryoid genotype-phenotype with the plasticity to transform their morphology on cell embryoblast-like memory entities by expression of dormant genes that arise from embryogenesis. After hundreds of driver mutations, cancer cells gain new abilities or attributes and recapitulate early stages of embryogenesis. Our findings document how malignant tissues reactivated ancestral storage memory and elaborate inside tumor glands spiral-pyramidal-fractal chiral crystals (Tc) as geometric attractor proteins and biomimicry the primitive cellular blastocyst embryoblast fluid-filled cavity. The resultant evolutionary embryoblast-like entity has higher survivability and spatial cephalic-caudal growth organization with pluripotentiality that carry the correct DNA instructions to repair, and regenerate. The isolation and manipulation of these order structures can guide and control the regenerative pathway mechanism in human tumors as follows: modify and reprogram the phenotype of the tumor where these entities are generated, establish a reverse primordial microscopic mold to use the swirlonic collective behavior of cellular building blocks to regenerate injured tissues, convert cancer cells to a normal phenotype through regeneration using the organizational level and scale properties of reverse genetic guidance, global control of mitotic activity and morphogenetic movements avoiding their spread and metastasis, determining a better life prognosis for patients who incubate these entities in their tumors compared to those who do not express them. An emergent self-repair order structure, biological template can develop targeted therapeutic alternatives not only in cancer but also in treatment of autoimmune, viral diseases, and in regenerative medicine and rejuvenation.

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