Exploring the role of mitochondria transfer/transplant and their long-non-coding RNAs in regenerative therapies for skin aging.

Advancing age and environmental stressors lead to mitochondrial dysfunction in the skin, inducing premature aging, impaired regeneration, and greater risk of cancer. Cells rely on the communication between the mitochondria and the nucleus by tight regulation of long non-coding RNAs (lncRNAs) to avoid premature aging and maintain healthy skin. LncRNAs act as key regulators of cell proliferation, differentiation, survival, and maintenance of skin structure. However, research on how the lncRNAs are dysregulated during aging and due to stressors is needed to develop therapies to regenerate skin's function and structure. In this article, we discuss how age and environmental stressors may alter lncRNA homeodynamics, compromising cell survival and skin health, and how these factors may become inducers of skin aging. We describe skin cell types and how they depend on mitochondrial function and lncRNAs. We also provide a list of mitochondria localized and nuclear lncRNAs that can serve to better understand skin aging. Using bioinformatic prediction tools, we predict possible functions of lncRNAs based on their subcellular localization. We also search for experimentally determined protein interactions and the biological processes involved. Finally, we provide therapeutic strategies based on gene editing and mitochondria transfer/transplant (AMT/T) to restore lncRNA regulation and skin health. This article offers a unique perspective in understanding and defining the therapeutic potential of mitochondria localized lncRNAs (mt-lncRNAs) and AMT/T to treat skin aging and related diseases.

Is bariatric surgery improving mitochondrial function in the renal cells of patients with obesity-induced kidney disease?

The role of mitochondria in health and disease has dramatically changed in the last decade. Its complex integration into cell physiology is comprised of key metabolic functions of great importance in health maintenance. Treating obesity seems to improve overall mitochondria tissue malfunction; however, the extent of their impact on patients remains elusive due to the lack of follow-up studies. It has been observed that procedures such as bariatric surgery (BS) can modify how our body absorbs nutrients, influencing metabolic processes and mitochondrial function in several cells and tissues. In fact, tissue analysis performed in vivo and in patients support that BS mitigates mitochondrial dysfunction in obese subjects. BS has been observed to reduce the presence of comorbidities such as type 2 diabetes (T2D) and hypertension (HTN) in patients. It is still unclear how BS specifically affects mitochondrial dynamics in obesity-induced comorbidities such as kidney disease. This article provides insightful information regarding the amelioration of mitochondrial dynamics in renal cells and systems after BS. Understanding the multiple pathways that lead to mitochondrial dysregulation in obesity-related kidney disease and relating them to the positive molecular changes after BS may lead to the development of adjuvant therapies to control this and other conditions with similar pathophysiological backgrounds.

Factors Associated with Vaccination Intention against the COVID-19 Pandemic: A Global Population-Based Study.

Several vaccines have been developed for COVID-19 since the pandemic began. This study aimed to evaluate the factors associated with COVID-19 vaccination intention. A global survey was conducted across 26 countries from October, 2020 to December, 2021 using an online self-administered questionnaire. Demographic information, socio-economic status, and clinical information were collected. A logistic regression examined the associations between vaccine intention and factors such as perceptions and the presence of chronic physical and mental conditions. The sample included 2459 participants, with 384 participants (15.7%) expressing lower COVID-19 vaccination intent. Individuals who identified as female; belonged to an older age group; had a higher level of education; were students; had full health insurance coverage; or had a previous history of influenza vaccination were more willing to receive vaccination. Conversely, those who were working part-time, were self-employed, or were receiving social welfare were less likely to report an intention to get vaccinated. Participants with mental or physical health conditions were more unwilling to receive vaccination, especially those with sickle cell disease, cancer history within the past five years, or mental illness. Stronger vaccination intent was associated with recommendations from the government or family doctors. The presence of chronic conditions was associated with lower vaccine intention. Individuals with health conditions are especially vulnerable to health complications and may experience an increased severity of COVID-19 symptoms. Future research should evaluate the effectiveness of interventions targeting the vaccine perceptions and behaviours of at-risk groups. As such, public awareness campaigns conducted by the government and proactive endorsement from health physicians may help improve COVID-19 vaccination intention.

Mesenchymal stem cell-mediated transfer of mitochondria: mechanisms and functional impact.

There is a steadily growing interest in the use of mitochondria as therapeutic agents. The use of mitochondria derived from mesenchymal stem/stromal cells (MSCs) for therapeutic purposes represents an innovative approach to treat many diseases (immune deregulation, inflammation-related disorders, wound healing, ischemic events, and aging) with an increasing amount of promising evidence, ranging from preclinical to clinical research. Furthermore, the eventual reversal, induced by the intercellular mitochondrial transfer, of the metabolic and pro-inflammatory profile, opens new avenues to the understanding of diseases' etiology, their relation to both systemic and local risk factors, and also leads to new therapeutic tools for the control of inflammatory and degenerative diseases. To this end, we illustrate in this review, the triggers and mechanisms behind the transfer of mitochondria employed by MSCs and the underlying benefits as well as the possible adverse effects of MSCs mitochondrial exchange. We relay the rationale and opportunities for the use of these organelles in the clinic as cell-based product.

Identification of key proteins in the signaling crossroads between wound healing and cancer hallmark phenotypes.

Wound healing (WH) and cancer seem to share common cellular and molecular processes that could work in a tight balance to maintain tissue homeostasis or, when unregulated, drive tumor progression. The "Cancer Hallmarks" comprise crucial biological properties that mediate the advancement of the disease and affect patient prognosis. These hallmarks have been proposed to overlap with essential features of the WH process. However, common hallmarks and proteins actively participating in both processes have yet to be described. In this work we identify 21 WH proteins strongly linked with solid tumors by integrated TCGA Pan-Cancer and multi-omics analyses. These proteins were associated with eight of the ten described cancer hallmarks, especially avoiding immune destruction. These results show that WH and cancer's common proteins are involved in the microenvironment modification of solid tissues and immune system regulation. This set of proteins, between WH and cancer, could represent key targets for developing therapies.

Breast cancer, screening and diagnostic tools: All you need to know.

Breast cancer is one of the most frequent malignancies among women worldwide. Methods for screening and diagnosis allow health care professionals to provide personalized treatments that improve the outcome and survival. Scientists and physicians are working side-by-side to develop evidence-based guidelines and equipment to detect cancer earlier. However, the lack of comprehensive interdisciplinary information and understanding between biomedical, medical, and technology professionals makes innovation of new screening and diagnosis tools difficult. This critical review gathers, for the first time, information concerning normal breast and cancer biology, established and emerging methods for screening and diagnosis, staging and grading, molecular and genetic biomarkers. Our purpose is to address key interdisciplinary information about these methods for physicians and scientists. Only the multidisciplinary interaction and communication between scientists, health care professionals, technical experts and patients will lead to the development of better detection tools and methods for an improved screening and early diagnosis.

Mesenchymal stem cell repression of Th17 cells is triggered by mitochondrial transfer.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells with broad immunosuppressive capacities. Recently, it has been reported that MSCs can transfer mitochondria to various cell types, including fibroblast, cancer, and endothelial cells. It has been suggested that mitochondrial transfer is associated with a physiological response to cues released by damaged cells to restore and regenerate damaged tissue. However, the role of mitochondrial transfer to immune competent cells has been poorly investigated. METHODS AND RESULTS: Here, we analyzed the capacity of MSCs from the bone marrow (BM) of healthy donors (BM-MSCs) to transfer mitochondria to primary CD4+CCR6+CD45RO+ T helper 17 (Th17) cells by confocal microscopy and fluorescent-activated cell sorting (FACS). We then evaluated the Th17 cell inflammatory phenotype and bioenergetics at 4 h and 24 h of co-culture with BM-MSCs. We found that Th17 cells can take up mitochondria from BM-MSCs already after 4 h of co-culture. Moreover, IL-17 production by Th17 cells co-cultured with BM-MSCs was significantly impaired in a contact-dependent manner. This inhibition was associated with oxygen consumption increase by Th17 cells and interconversion into T regulatory cells. Finally, by co-culturing human synovial MSCs (sMSCs) from patients with rheumatoid arthritis (RA) with Th17 cells, we found that compared with healthy BM-MSCs, mitochondrial transfer to Th17 cells was impaired in RA-sMSCs. Moreover, artificial mitochondrial transfer also significantly reduced IL-17 production by Th17 cells. CONCLUSIONS: The present study brings some insights into a novel mechanism of T cell function regulation through mitochondrial transfer from stromal stem cells. The reduced mitochondrial transfer by RA-sMSCs might contribute to the persistence of chronic inflammation in RA synovitis.

Primary allogeneic mitochondrial mix (PAMM) transfer/transplant by MitoCeption to address damage in PBMCs caused by ultraviolet radiation.

BACKGROUND: Artificial Mitochondrial Transfer or Transplant (AMT/T) can be used to reduce the stress and loss of viability of damaged cells. In MitoCeption, a type of AMT/T, the isolated mitochondria and recipient cells are centrifuged together at 4 °C and then co-incubated at 37 °C in normal culture conditions, inducing the transfer. Ultraviolet radiation (UVR) can affect mitochondria and other cell structures, resulting in tissue stress, aging, and immunosuppression. AMT/T could be used to repair UVR cellular and mitochondrial damage. We studied if a mitochondrial mix from different donors (Primary Allogeneic Mitochondrial Mix, PAMM) can repair UVR damage and promote cell survival. RESULTS: Using a simplified adaption of the MitoCeption protocol, we used peripheral blood mononuclear cells (PBMCs) as the recipient cell model of the PAMM in order to determine if this protocol could repair UVR damage. Our results showed that when PBMCs are exposed to UVR, there is a decrease in metabolic activity, mitochondrial mass, and mtDNA sequence stability as well as an increase in p53 expression and the percentage of dead cells. When PAMM MitoCeption was used on UVR-damaged cells, it successfully transferred mitochondria from different donors to distinct PBMCs populations and repaired the observed UVR damage. CONCLUSION: Our results represent an advancement in the applications of MitoCeption and other AMT/T. We showed that PBMCs could be used as a PAMM source of mitochondria. We also showed that these mitochondria can be transferred in a mix from different donors (PAMM) to UVR-damaged, non-adherent primary cells. Additionally, we decreased the duration of the MitoCeption protocol.

Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy.

Intercellular communications play a major role in tissue homeostasis and responses to external cues. Novel structures for this communication have recently been described. These tunneling nanotubes (TNTs) consist of thin-extended membrane protrusions that connect cells together. TNTs allow the cell-to-cell transfer of various cellular components, including proteins, RNAs, viruses, and organelles, such as mitochondria. Mesenchymal stem cells (MSCs) are both naturally present and recruited to many different tissues where their interaction with resident cells via secreted factors has been largely documented. Their immunosuppressive and repairing capacities constitute the basis for many current clinical trials. MSCs recruited to the tumor microenvironment also play an important role in tumor progression and resistance to therapy. MSCs are now the focus of intense scrutiny due to their capacity to form TNTs and transfer mitochondria to target cells, either in normal physiological or in pathological conditions, leading to changes in cell energy metabolism and functions, as described in this review.

Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment.

Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors. As a result, CSCs can recurrently persist after therapy. In order to understand how the concept of stemness applies to cancer, this review will explore properties shared between normal and malignant Stem Cells. First, we provide an overview of properties of normal adult Stem Cells. We thereafter elaborate on how these features operate in CSCs. We then review the organization of microenvironment components, which enables CSCs hosting. We subsequently discuss Mesenchymal Stem/Stromal Cells (MSCs), which, although their stemness properties are limited, represent essential components of the Stem Cell niche and tumor microenvironment. We next provide insights of the therapeutic strategies targeting Stem Cell properties in tumors and the use of state-of-the-art techniques in future research. Increasing our knowledge of the CSCs microenvironment is key to identifying new therapeutic solutions.

Enfermedad de Chagas y su seroprevalencia en tres departamentos de la Amazonia colombiana / Chagas disease and its seroprevalence in three departments of the Colombian Amazon

Objetivo. Determinar la seroprevalencia de la enfermedad de Chagas en población general procedente de tres departamentos de la Amazonía colombiana: Vaupés, Amazonas y Guaviare y analizar variables de riesgo para la enfermedad. Métodos. Para determinar la seropositividad se analizaron 3429 muestras de suero obtenidas mediante previo consentimiento informado durante los años 2009 y 2010 a través de un muestreo probabilístico, de conglomerados, estratificado y trietápico para cada departamento, con probabilidades finales desiguales. Fueron analizadas en el Laboratorio de Parasitología del Instituto Nacional de Salud de Bogotá mediante dos técnicas de diagnóstico, Inmunoensayo enzimático (Elisa) e Inmunofluorescencia indirecta (IFI) empleando como antígeno una cepa de Trypanosoma cruzi colombiana previamente caracterizada como linaje TcI. Resultados. Se encontró una seroprevalencia general de 0,99%, 2,07% para el departamento del Guaviare, 0,79% para el departamento de Vaupés y 0,09% para el departamento de Amazonas. Estos resultados permitirán establecer una línea de base epidemiológica que contribuya a las estrategias de control de la enfermedad en esta zona.

Objective. To estimate the prevalence of Chagas disease in population from Vaupés, Amazonas and Guaviare, three departments of the Colombian amazon. Risk factors were also assessed. Methods. For estimating seroprevalence, 3429 serum samples were taken according to a three-stage conglomerate sampling for each department. Those samples were analyzed in the Parasitology Laboratory of the National Health Institute (INS), through ELISA and IFAT techniques. Results. The prevalence for Amazonas, Guaviare and Vaupés departments was 0,09%, 2,07% and 0,79%, respectively. Those results will allow health policy makers towards prevention of Chagas disease.

IL-1ß produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production.

The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen-receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-κB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IκB dominant negative mutant, nuclear translocation of p65 and induction of NF-κB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL-1ß, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1ß secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA-MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL-1ß, which increases the production of chemokines by MSCs.

MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function.

Mitochondrial activity is central to tissue homeostasis. Mitochondria dysfunction constitutes a hallmark of many genetic diseases and plays a key role in tumor progression. The essential role of mitochondria, added to their recently documented capacity to transfer from cell to cell, obviously contributes to their current interest. However, determining the proper role of mitochondria in defined biological contexts was hampered by the lack of suitable experimental tools. We designed a protocol (MitoCeption) to directly and quantitatively transfer mitochondria, isolated from cell type A, to recipient cell type B. We validated and quantified the effective mitochondria transfer by imaging, fluorescence-activated cell sorting (FACS) and mitochondrial DNA analysis. We show that the transfer of minute amounts of mesenchymal stem/stromal cell (MSC) mitochondria to cancer cells, a process otherwise occurring naturally in coculture, results in cancer cell enhanced oxidative phosphorylation (OXPHOS) activity and favors cancer cell proliferation and invasion. The MitoCeption technique, which can be applied to different cell systems, will therefore be a method of choice to analyze the metabolic modifications induced by exogenous mitochondria in host cells.

Coxsackie and adenovirus receptor is a target and a mediator of estrogen action in breast cancer.

The involvement of the coxsackie and adenovirus receptor (CAR), an adhesion molecule known to be the main determinant of adenovirus transduction of the cells, in cancer is currently under investigation. Recent reports suggest that CAR levels are elevated in breast cancer, and this may have an impact on its use as means of delivery for gene therapy. In this study, we show that estradiol (E(2)) treatment of the estrogen receptor (ER)-positive breast cancer cell MCF-7 increases CAR levels and, in turn, enhances adenoviral transduction. Employing the transfection of CAR promoters in breast cancer cells, we show that this regulation of CAR expression occurs at the transcriptional level. In addition, and by chromatin immunoprecipitation, we have identified a crucial region of CAR promoter that controls E(2) responsiveness of CAR gene through the recruitment of ER. Moreover, utilizing CAR antibodies or CAR silencing by RNA interference repressed the estrogen-dependent growth of breast cancer cells, whereas the stable expression of CAR in MCF-7 or MDA-MB-231 cells led to an increased proliferation. Altogether, our data suggest that CAR is a novel estrogen-responsive gene, which is involved in the E(2)-dependent proliferation of breast cancer cells.

Colangiografía transoperatoria selectiva o rutinaria?

Se realiza un estudio prospectivo en 40 pacientes con diagnóstico de colecistolitiasis, en el Servicio de Cirugía General del Hospital Eugenio Espejo, de Quito, Ecuador, durante el período comprendido entre el 1ro de Agosto de 1991 y el 30 de abril de 1992, con el objeto de establecer si la colangiografía transoperatoria debe ser un procedimiento selectivo o rutinario. Los resultados obtenidos muestran diferencias con relación a la presencia de cálculos no sospechados en la vía biliar, entre los pacientes sometidos a colangiografía transoperatoria que tuvieron indicaciones y aquellos sin indicaciones. El análisis estadístico correspondiente reveló que los mismos son significativos. Los datos sugieren, que la colangiografía transoperatoria debe ser realizada sólo de manera selectiva. El método de estudio seleccionado fué optimo y no se encontró ninguna complicación en la realización de las colangiografías, ni en su posterior análisis, de manera que los resultados que se obtuvieron son seguros y confiables. Sería conveniente realizar en el futuro un estudio comparativo y prospectivo entre los diferentes hospitales de Quito.