Environmental regulation of placental phenotype: implications for fetal growth

Environmental conditions during pregnancy determine birthweight, neonatal viability and adult phenotype in human and other animals. In part, these effects may be mediated by the placenta, the principal source of nutrients for fetal development. However, little is known about the environmental regulation of placental phenotype. Generally, placental weight is reduced during suboptimal conditions like maternal malnutrition or hypoxaemia but compensatory adaptations can occur in placental nutrient transport capacity to help maintain fetal growth. In vivo studies show that transplacental glucose and amino acid transfer adapt to the prevailing conditions induced by manipulating maternal calorie intake, dietary composition and hormone exposure. These adaptations are due to changes in placental morphology, metabolism and/or abundance of specific nutrient transporters. This review examines environmental programming of placental phenotype with particular emphasis on placental nutrient transport capacity and its implications for fetal growth, mainly in rodents. It also considers the systemic, cellular and molecular mechanisms involved in signalling environmental cues to the placenta. Ultimately, the ability of the placenta to balance the competing interests of mother and fetus in resource allocation may determine not only the success of pregnancy in producing viable neonates but also the long-term health of the offspring.

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Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

International Journal of Molecular Sciences ◽

10.3390/ijms22136663 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6663

Author(s):

Maurycy Jankowski ◽

Mariusz Kaczmarek ◽

Grzegorz Wąsiatycz ◽

Claudia Dompe ◽

Paul Mozdziak ◽

...

Keyword(s):

Stem Cells ◽

In Vitro Culture ◽

Osteogenic Differentiation ◽

Molecular Mechanisms ◽

Marker Genes ◽

P Value ◽

Illumina Platform

Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic differentiation of ASCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture and osteogenic differentiation of ASCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ASCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells’ application in regenerative medicine.

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Time-Programmed Delivery of Sorafenib and Anti-CD47 Antibody via a Double-Layer-Gel Matrix for Postsurgical Treatment of Breast Cancer

Nano-Micro Letters ◽

10.1007/s40820-021-00647-x ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Liping Huang ◽

Yiyi Zhang ◽

Yanan Li ◽

Fanling Meng ◽

Hongyu Li ◽

...

Keyword(s):

Breast Cancer ◽

Near Infrared ◽

Immune Escape ◽

Regulatory Protein ◽

In Vivo Studies ◽

Breast Cancer Patients ◽

Thermally Responsive ◽

Immunosuppressive Microenvironment

AbstractThe highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients. Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising, yet greatly challenging, to reverse postoperative immunosuppression. Here, an injectable hierarchical gel matrix, composed of dual lipid gel (DLG) layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios, was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy. The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide (GO) nanoparticles. GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages (TAMs) and promote an immunogenic tumor microenvironment. The inner layer, loaded with anti-CD47 antibody (aCD47), could maintain the gel state for a much longer time, enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory protein α (SIRPα) pathway for a long-term antitumor effect. In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape, thereby boosting the systemic immune responses.

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The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study

Cancers ◽

10.3390/cancers13133169 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3169

Author(s):

Kevin Doello ◽

Cristina Mesas ◽

Francisco Quiñonero ◽

Gloria Perazzoli ◽

Laura Cabeza ◽

...

Keyword(s):

Pancreatic Cancer ◽

Sodium Selenite ◽

Molecular Mechanisms ◽

Combined Therapy ◽

Significant Inhibition ◽

In Vivo Studies ◽

C57bl Mice ◽

Migration Capacity

Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.

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Unraveling the neurotoxicity of titanium dioxide nanoparticles: focusing on molecular mechanisms

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.7.57 ◽

2016 ◽

Vol 7 ◽

pp. 645-654 ◽

Cited By ~ 17

Author(s):

Bin Song ◽

Yanli Zhang ◽

Jia Liu ◽

Xiaoli Feng ◽

Ting Zhou ◽

...

Keyword(s):

Dna Methylation ◽

Titanium Dioxide ◽

Molecular Mechanisms ◽

Titanium Dioxide Nanoparticles ◽

Brain Dysfunction ◽

In Vivo Studies ◽

Cell Components ◽

New Perspective ◽

The Brain

Titanium dioxide nanoparticles (TiO2 NPs) possess unique characteristics and are widely used in many fields. Numerous in vivo studies, exposing experimental animals to these NPs through systematic administration, have suggested that TiO2 NPs can accumulate in the brain and induce brain dysfunction. Nevertheless, the exact mechanisms underlying the neurotoxicity of TiO2 NPs remain unclear. However, we have concluded from previous studies that these mechanisms mainly consist of oxidative stress (OS), apoptosis, inflammatory response, genotoxicity, and direct impairment of cell components. Meanwhile, other factors such as disturbed distributions of trace elements, disrupted signaling pathways, dysregulated neurotransmitters and synaptic plasticity have also been shown to contribute to neurotoxicity of TiO2 NPs. Recently, studies on autophagy and DNA methylation have shed some light on possible mechanisms of nanotoxicity. Therefore, we offer a new perspective that autophagy and DNA methylation could contribute to neurotoxicity of TiO2 NPs. Undoubtedly, more studies are needed to test this idea in the future. In short, to fully understand the health threats posed by TiO2 NPs and to improve the bio-safety of TiO2 NPs-based products, the neurotoxicity of TiO2 NPs must be investigated comprehensively through studying every possible molecular mechanism.

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An Update on the Role of Dietary Phytochemicals in Human Skin Cancer: New Insights into Molecular Mechanisms

Antioxidants ◽

10.3390/antiox9100916 ◽

2020 ◽

Vol 9 (10) ◽

pp. 916 ◽

Cited By ~ 1

Author(s):

Salman Ul Islam ◽

Muhammad Bilal Ahmed ◽

Haseeb Ahsan ◽

Mazharul Islam ◽

Adeeb Shehzad ◽

...

Keyword(s):

Skin Cancer ◽

Human Skin ◽

Cancer Progression ◽

Fruits And Vegetables ◽

Molecular Mechanisms ◽

In Vivo Studies ◽

Skin Malignancy ◽

Dietary Phytochemicals

Human skin is continuously subjected to environmental stresses, as well as extrinsic and intrinsic noxious agents. Although skin adopts various molecular mechanisms to maintain homeostasis, excessive and repeated stresses can overwhelm these systems, leading to serious cutaneous damage, including both melanoma and non-melanoma skin cancers. Phytochemicals present in the diet possess the desirable effects of protecting the skin from damaging free radicals as well as other benefits. Dietary phytochemicals appear to be effective in preventing skin cancer and are inexpensive, widely available, and well tolerated. Multiple in vitro and in vivo studies have demonstrated the significant anti-inflammatory, antioxidant, and anti-angiogenic characteristics of dietary phytochemicals against skin malignancy. Moreover, dietary phytochemicals affect multiple important cellular processes including cell cycle, angiogenesis, and metastasis to control skin cancer progression. Herein, we discuss the advantages of key dietary phytochemicals in whole fruits and vegetables, their bioavailability, and underlying molecular mechanisms for preventing skin cancer. Current challenges and future prospects for research are also reviewed. To date, most of the chemoprevention investigations have been conducted preclinically, and additional clinical trials are required to conform and validate the preclinical results in humans.

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Long Term Pharmacological Perturbation of Autophagy in Mice: Are HCQ Injections a Relevant Choice?

Biomedicines ◽

10.3390/biomedicines8030047 ◽

2020 ◽

Vol 8 (3) ◽

pp. 47 ◽

Cited By ~ 1

Author(s):

Jean-Daniel Masson ◽

Benoit Blanchet ◽

Baptiste Periou ◽

François-Jérôme Authier ◽

Baharia Mograbi ◽

...

Keyword(s):

Mouse Models ◽

In Vivo Studies ◽

Loss Of Function ◽

Evolutionarily Conserved ◽

Atg Genes ◽

Conditional Inhibition ◽

The Impact ◽

Catabolic Process

Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved catabolic process whose loss-of-function has been linked to a growing list of pathologies. Knockout mouse models of key autophagy genes have been instrumental in the demonstration of the critical functions of autophagy, but they display early lethality, neurotoxicity and unwanted autophagy-independent phenotypes, limiting their applications for in vivo studies. To avoid problems encountered with autophagy-null transgenic mice, we investigated the possibility of disturbing autophagy pharmacologically in the long term. Hydroxychloroquine (HCQ) ip injections were done in juvenile and adult C57bl/6j mice, at range doses adapted from the human malaria prophylactic treatment. The impact on autophagy was assessed by western-blotting, and juvenile neurodevelopment and adult behaviours were evaluated for four months. Quite surprisingly, our results showed that HCQ treatment in conditions used in this study neither impacted autophagy in the long term in several tissues and organs nor altered neurodevelopment, adult behaviour and motor capabilities. Therefore, we recommend for future long-term in vivo studies of autophagy, to use genetic mouse models allowing conditional inhibition of selected Atg genes in appropriate lineage cells instead of HCQ treatment, until it could be successfully revisited using higher HCQ doses and/or frequencies with acceptable toxicity.

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3D-bioprinted tracheal reconstruction: an overview

Bioelectronic Medicine ◽

10.1186/s42234-019-0031-1 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Lidia Frejo ◽

Daniel A. Grande

Keyword(s):

In Vivo Studies ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Tracheal Reconstruction ◽

Airway Reconstruction ◽

Life Threatening ◽

Scaffold Materials ◽

Cellular Types

Abstract Congenital tracheomalacia and tracheal stenosis are commonly seen in premature infants. In adulthood, are typically related with chronic obstructive pulmonary disease, and can occur secondarily from tracheostomy, prolong intubation, trauma, infection and tumors. Both conditions are life-threatening when not managed properly. There are still some surgical limitations for certain pathologies, however tissue engineering is a promising approach to treat massive airway dysfunctions. 3D-bioprinting have contributed to current preclinical and clinical efforts in airway reconstruction. Several strategies have been used to overcome the difficulty of airway reconstruction such as scaffold materials, construct designs, cellular types, biologic components, hydrogels and animal models used in tracheal reconstruction. Nevertheless, additional long-term in vivo studies need to be performed to assess the efficacy and safety of tissue-engineered tracheal grafts in terms of mechanical properties, behavior and, the possibility of further stenosis development.

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Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Molecules ◽

10.3390/molecules25030596 ◽

2020 ◽

Vol 25 (3) ◽

pp. 596 ◽

Cited By ~ 3

Author(s):

María del Carmen Villegas-Aguilar ◽

Álvaro Fernández-Ochoa ◽

María de la Luz Cádiz-Gurrea ◽

Sandra Pimentel-Moral ◽

Jesús Lozano-Sánchez ◽

...

Keyword(s):

Energy Metabolism ◽

Phenolic Compounds ◽

Molecular Mechanisms ◽

Biological Effects ◽

Biological Properties ◽

In Vivo Studies ◽

Wide Range ◽

High Prevalence

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

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Yeast as a Model to Understand Actin-Mediated Cellular Functions in Mammals—Illustrated with Four Actin Cytoskeleton Proteins

Cells ◽

10.3390/cells9030672 ◽

2020 ◽

Vol 9 (3) ◽

pp. 672 ◽

Cited By ~ 1

Author(s):

Zain Akram ◽

Ishtiaq Ahmed ◽

Heike Mack ◽

Ramandeep Kaur ◽

Richard C. Silva ◽

...

Keyword(s):

Actin Cytoskeleton ◽

Molecular Mechanisms ◽

Budding Yeast ◽

Animal Cell ◽

Molecular Genetic ◽

In Vivo Studies ◽

Yeast Saccharomyces Cerevisiae ◽

Higher Eukaryotes

The budding yeast Saccharomyces cerevisiae has an actin cytoskeleton that comprises a set of protein components analogous to those found in the actin cytoskeletons of higher eukaryotes. Furthermore, the actin cytoskeletons of S. cerevisiae and of higher eukaryotes have some similar physiological roles. The genetic tractability of budding yeast and the availability of a stable haploid cell type facilitates the application of molecular genetic approaches to assign functions to the various actin cytoskeleton components. This has provided information that is in general complementary to that provided by studies of the equivalent proteins of higher eukaryotes and hence has enabled a more complete view of the role of these proteins. Several human functional homologues of yeast actin effectors are implicated in diseases. A better understanding of the molecular mechanisms underpinning the functions of these proteins is critical to develop improved therapeutic strategies. In this article we chose as examples four evolutionarily conserved proteins that associate with the actin cytoskeleton: (1) yeast Hof1p/mammalian PSTPIP1, (2) yeast Rvs167p/mammalian BIN1, (3) yeast eEF1A/eEF1A1 and eEF1A2 and (4) yeast Yih1p/mammalian IMPACT. We compare the knowledge on the functions of these actin cytoskeleton-associated proteins that has arisen from studies of their homologues in yeast with information that has been obtained from in vivo studies using live animals or in vitro studies using cultured animal cell lines.

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Nutraceuticals for the Treatment of Diabetic Retinopathy

Nutrients ◽

10.3390/nu11040771 ◽

2019 ◽

Vol 11 (4) ◽

pp. 771 ◽

Cited By ~ 20

Author(s):

Maria Grazia Rossino ◽

Giovanni Casini

Keyword(s):

Diabetic Retinopathy ◽

Molecular Mechanisms ◽

Treatment Options ◽

Vitreoretinal Surgery ◽

In Vivo Studies ◽

Early Diabetes ◽

Advanced Stages ◽

Endothelial Growth Factor

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and is characterized by degeneration of retinal neurons and neoangiogenesis, causing a severe threat to vision. Nowadays, the principal treatment options for DR are laser photocoagulation, vitreoretinal surgery, or intravitreal injection of drugs targeting vascular endothelial growth factor. However, these treatments only act at advanced stages of DR, have short term efficacy, and cause side effects. Treatment with nutraceuticals (foods providing medical or health benefits) at early stages of DR may represent a reasonable alternative to act upstream of the disease, preventing its progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DR, reducing both the neural and vascular damage typical of DR. Although most studies are limited to animal models and there is the problem of low bioavailability for many nutraceuticals, the use of these compounds may represent a natural alternative method to standard DR treatments.

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