Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the main causes of death by cancer worldwide, representing about 80-90% of all liver cancers. Treatments available for advanced HCC include atezolizumab, bevacizumab, sorafenib, among others. Atezolizumab and bevacizumab are immunological options recently incorporated into first-line treatments, along with sorafenib, for which great treatment achievements have been reached. However, sorafenib resistance is developed in most patients, and therapeutical combinations targeting cancer hallmark mechanisms and intracellular signaling have been proposed. In this review, we compiled evidence of the mechanisms of cell death caused by sorafenib administered alone or in combination with valproic acid and metformin and discussed them from a molecular perspective.

The Placenta as a Target for Alcohol During Pregnancy: The Close Relation with IGFs Signaling Pathway.

Alcohol is one of the most consumed drugs in the world, even during pregnancy. Its use is a risk factor for developing adverse outcomes, e.g. fetal death, miscarriage, fetal growth restriction, and premature birth, also resulting in fetal alcohol spectrum disorders. Ethanol metabolism induces an oxidative environment that promotes the oxidation of lipids and proteins, triggers DNA damage, and advocates mitochondrial dysfunction, all of them leading to apoptosis and cellular injury. Several organs are altered due to this harmful behavior, the brain being one of the most affected. Throughout pregnancy, the human placenta is one of the most important organs for women's health and fetal development, as it secretes numerous hormones necessary for a suitable intrauterine environment. However, our understanding of the human placenta is very limited and even more restricted is the knowledge of the impact of toxic substances in its development and fetal growth. So, could ethanol consumption during this period have wounding effects in the placenta, compromising proper fetal organ development? Several studies have demonstrated that alcohol impairs various signaling cascades within G protein-coupled receptors and tyrosine kinase receptors, mainly through its action on insulin and insulin-like growth factor 1 (IGF-1) signaling pathway. This last cascade is involved in cell proliferation, migration, and differentiation and in placentation. This review tries to examine the current knowledge and gaps in our existing understanding of the ethanol effects in insulin/IGFs signaling pathway, which can explain the mechanism to elucidate the adverse actions of ethanol in the maternal-fetal interface of mammals.

Exploring knowledge of parents and caregivers on cancer symptoms in children: an observational study regarding the need for educational tools and health promotion in low- and middle-income countries.

BACKGROUND: Although most cases of childhood cancer are unlikely to be prevented, by today's standards, most children with cancer can now be cured. However, disparities about survival exist among countries; in Mexico, the overall survival is 49.6%, with 70% of childhood cancers diagnosed at advanced stages. Therefore, parents and caregivers must have optimal knowledge of the early signs and symptoms of childhood malignancies as they are largely non-specific. This study was designed to explore the current knowledge of childhood cancer among parents and caregivers in Mexico and identify the need for education and health promotion in low- and middle-income countries. METHODS: An online survey of 112 parents and caregivers was performed to assess their knowledge of childhood cancer, focusing on the signs and symptoms and early diagnostic strategies. RESULTS: Sixty-nine (61.6%) mothers, 23 (20.5%) fathers, 17 (15.2%) familiar caregivers, and 3 (2.7%) non-familiar caregivers responded. Forty-six (41.1%) respondents said that they knew a child diagnosed with cancer, 92.9% mentioned leukemia as the most common type of cancer among children, the most highly ranked option when asked which sign/symptom they considered as a warning for suspicion was growth/lump in any part of the body, 97.3% considered that an early diagnosis is related to a higher cure rate, and 92.9% expressed the desire to receive reliable information about childhood cancer. CONCLUSIONS: Although parents and caregivers have some knowledge of childhood cancer, there are concepts that should be reinforced to improve their understanding of this group of diseases, as they are the frontline for children to seek medical attention. In the future, the use of tools that help educate more caregivers will strengthen knowledge and contribution regarding this issue and promote the generation of public policies that support the early diagnosis of childhood cancer.

Genome editing in fruit, ornamental, and industrial crops.

The advent of genome editing has opened new avenues for targeted trait enhancement in fruit, ornamental, industrial, and all specialty crops. In particular, CRISPR-based editing systems, derived from bacterial immune systems, have quickly become routinely used tools for research groups across the world seeking to edit plant genomes with a greater level of precision, higher efficiency, reduced off-target effects, and overall ease-of-use compared to ZFNs and TALENs. CRISPR systems have been applied successfully to a number of horticultural and industrial crops to enhance fruit ripening, increase stress tolerance, modify plant architecture, control the timing of flower development, and enhance the accumulation of desired metabolites, among other commercially-important traits. As editing technologies continue to advance, so too does the ability to generate improved crop varieties with non-transgenic modifications; in some crops, direct transgene-free edits have already been achieved, while in others, T-DNAs have successfully been segregated out through crossing. In addition to the potential to produce non-transgenic edited crops, and thereby circumvent regulatory impediments to the release of new, improved crop varieties, targeted gene editing can speed up trait improvement in crops with long juvenile phases, reducing inputs resulting in faster market introduction to the market. While many challenges remain regarding optimization of genome editing in ornamental, fruit, and industrial crops, the ongoing discovery of novel nucleases with niche specialties for engineering applications may form the basis for additional and potentially crop-specific editing strategies.

Fruit crops in the era of genome editing: closing the regulatory gap.

The conventional breeding of fruits and fruit trees has led to the improvement of consumer-driven traits such as fruit size, yield, nutritional properties, aroma and taste, as well as the introduction of agronomic properties such as disease resistance. However, even with the assistance of modern molecular approaches such as marker-assisted selection, the improvement of fruit varieties by conventional breeding takes considerable time and effort. The advent of genetic engineering led to the rapid development of new varieties by allowing the direct introduction of genes into elite lines. In this review article, we discuss three such case studies: the Arctic® apple, the Pinkglow pineapple and the SunUp/Rainbow papaya. We consider these events in the light of global regulations for the commercialization of genetically modified organisms (GMOs), focusing on the differences between product-related systems (the USA/Canada comparative safety assessment) and process-related systems (the EU "precautionary principle" model). More recently, genome editing has provided an efficient way to introduce precise mutations in plants, including fruits and fruit trees, replicating conventional breeding outcomes without the extensive backcrossing and selection typically necessary to introgress new traits. Some jurisdictions have reacted by amending the regulations governing GMOs to provide exemptions for crops that would be indistinguishable from conventional varieties based on product comparison. This has revealed the deficiencies of current process-related regulatory frameworks, particularly in the EU, which now stands against the rest of the world as a unique example of inflexible and dogmatic governance based on political expediency and activism rather than rigorous scientific evidence.

5-Aza-2'-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells.

A generation of induced pluripotent stem cells (iPSC) by ectopic expression of OCT4, SOX2, KLF4, and c-MYC has established promising opportunities for stem cell research, drug discovery, and disease modeling. While this forced genetic expression represents an advantage, there will always be an issue with genomic instability and transient pluripotency genes reactivation that might preclude their clinical application. During the reprogramming process, a somatic cell must undergo several epigenetic modifications to induce groups of genes capable of reactivating the endogenous pluripotency core. Here, looking to increase the reprograming efficiency in somatic cells, we evaluated the effect of epigenetic molecules 5-aza-2'-deoxycytidine (5AZ) and valproic acid (VPA) and two small molecules reported as reprogramming enhancers, CHIR99021 and A83-01, on the expression of pluripotency genes and the methylation profile of the OCT4 promoter in a human dermal fibroblasts cell strain. The addition of this cocktail to culture medium increased the expression of OCT4, SOX2, and KLF4 expression by 2.1-fold, 8.5-fold, and 2-fold, respectively, with respect to controls; concomitantly, a reduction in methylated CpG sites in OCT4 promoter region was observed. The epigenetic cocktail also induced the expression of the metastasis-associated gene S100A4. However, the epigenetic cocktail did not induce the morphological changes characteristic of the reprogramming process. In summary, 5AZ, VPA, CHIR99021, and A83-01 induced the expression of OCT4 and SOX2, two critical genes for iPSC. Future studies will allow us to precise the mechanisms by which these compounds exert their reprogramming effects.

Selenite Downregulates STAT3 Expression and Provokes Lymphocytosis in the Liver of Chronically Exposed Syrian Golden Hamsters.

Arsenic is considered a worldwide pollutant that can be present in drinking water. Arsenic exposure is associated with various diseases, including cancer. Antioxidants as selenite and α-tocopherol-succinate have been shown to modulate arsenic toxic effects. Since changes in STAT3 and PSMD10 gene expression have been associated with carcinogenesis, the aim of this study was to evaluate the effect of arsenic exposure and co-treatments with selenite or α-tocopherol-succinate on the expression of these genes, in the livers of chronically exposed Syrian golden hamsters. Animals were divided into six groups: (i) control, (ii) chronically treated with 100 ppm arsenic, (iii) treated with 6 ppm α-tocopherol-succinate (α-TOS), (iv) treated with 8.5 ppm selenite, (v) treated with arsenic + α-TOS, and (vi) treated with arsenic + selenite. Urine samples and livers were collected after 20 weeks of continuous exposure. The urine samples were analyzed for arsenic species by atomic absorption spectrophotometry, and real-time RT-qPCR analysis was performed for gene expression evaluation. A reduction in STAT3 expression was observed in the selenite-treated group. No differences in PSMD10 expression were found among groups. Histopathological analysis revealed hepatic lymphocytosis in selenite-treated animals. As a conclusion, long-term exposure to arsenic does not significantly alter the expression of STAT3 and PSMD10 oncogenes in the livers of hamsters; however, selenite down-regulates STAT3 expression and provokes lymphocytosis.

Isotretinoin and Thalidomide Down-Regulate c-MYC Gene Expression and Modify Proteins Associated with Cancer in Hepatic Cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.

Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases.

Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy-Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.

CRISPR-associated nucleases: the Dawn of a new age of efficient crop improvement.

The world stands at a new threshold today. As a planet, we face various challenges, and the key one is how to continue to produce enough food, feed, fiber, and fuel to support the burgeoning population. In the past, plant breeding and the ability to genetically engineer crops contributed to increasing food production. However, both approaches rely on random mixing or integration of genes, and the process can be unpredictable and time-consuming. Given the challenge of limited availability of natural resources and changing environmental conditions, the need to rapidly and precisely improve crops has become urgent. The discovery of CRISPR-associated endonucleases offers a precise yet versatile platform for rapid crop improvement. This review summarizes a brief history of the discovery of CRISPR-associated nucleases and their application in genome editing of various plant species. Also provided is an overview of several new endonucleases reported recently, which can be utilized for editing of specific genes in plants through various forms of DNA sequence alteration. Genome editing, with its ever-expanding toolset, increased efficiency, and its potential integration with the emerging synthetic biology approaches hold promise for efficient crop improvement to meet the challenge of supporting the needs of future generations.

In Silico Analysis and In Vitro Characterization of the Bioactive Profile of Three Novel Peptides Identified from 19 kDa α-Zein Sequences of Maize.

In this study, we characterized three novel peptides derived from the 19 kDa α-zein, and determined their bioactive profile in vitro and developed a structural model in silico. The peptides, 19ZP1, 19ZP2 and 19ZP3, formed α-helical structures and had positive and negative electrostatic potential surfaces (range of -1 to +1). According to the in silico algorithms, the peptides displayed low probabilities for cytotoxicity (≤0.05%), cell penetration (10-33%) and antioxidant activities (9-12.5%). Instead, they displayed a 40% probability for angiotensin-converting enzyme (ACE) inhibitory activity. For in vitro characterization, peptides were synthesized by solid phase synthesis and tested accordingly. We assumed α-helical structures for 19ZP1 and 19ZP2 under hydrophobic conditions. The peptides displayed antioxidant activity and ACE-inhibitory activity, with 19ZP1 being the most active. Our results highlight that the 19 kDa α-zein sequences could be explored as a source of bioactive peptides, and indicate that in silico approaches are useful to predict peptide bioactivities, but more structural analysis is necessary to obtain more accurate data.

Antioxidant Activity of Zein Hydrolysates from Zea Species and Their Cytotoxic Effects in a Hepatic Cell Culture.

In recent years, food proteins with bioactivity have been studied for cancer treatment. Zein peptides have shown an important set of bioactivities. This work compares the cytotoxic activity of zein hydrolyzed, extracted from four Zea species: teosinte, native, hybrid, and transgenic (Teo, Nat, Hyb, and HT) in a hepatic cell culture. Zein fraction was extracted, quantified, and hydrolyzed. Antioxidant capacity and cytotoxicity assays were performed on HepG2 cells. The levels of expression of caspase 3, 8, and 9 were evaluated in zein-treated cell cultures. Zea parviglumis showed the highest zein content (46.0 mg/g) and antioxidant activity (673.40 TE/g) out of all native zeins. Peptides from Hyb and HT showed high antioxidant activity compared to their native counterparts (1055.45 and 724.32 TE/g, respectively). Cytotoxic activity was observed in the cell culture using peptides of the four Zea species; Teo and Nat (IC50: 1781.63 and 1546.23 ng/mL) had no significant difference between them but showed more cytotoxic activity than Hyb and HT (IC50: 1252.25 and 1155.56 ng/mL). Increased expression of caspase 3 was observed in the peptide-treated HepG2 cells (at least two-fold more with respect to the control sample). These data indicate the potential for zein peptides to prevent or treat cancer, possibly by apoptosis induction.

Isotopologue profiling of triterpene formation under physiological conditions. Biosynthesis of lupeol-3-(3'-R-hydroxy)-stearate in Pentalinon andrieuxii.

The biosynthesis of lupeol-3-(3'R-hydroxy)-stearate (procrim b, 1) was investigated in the Mexican medicinal plant Pentalinon andrieuxii by (13)CO2 pulse-chase experiments. NMR analyses revealed positional enrichments of (13)C2-isotopologues in both the triterpenoid and the hydroxystearate moieties of 1. Five of the six isoprene units reflected a pattern with [1,2-(13)C2]- and [3,5-(13)C2]-isotopologues from the respective C5-precursors, IPP and DMAPP, whereas one isoprene unit in the ring E of 1 showed only the [3,5-(13)C2]-connectivity of the original C5-precursor, due to rearrangement of the dammarenyl cation intermediate during the cyclization process. The presence of (13)C2-isotopologues was indicative of [(13)C2]acetyl-CoA being the precursor units in the formation of the fatty acid moiety and of the triterpene via the mevalonate route. The observed labeling pattern was in agreement with a chair-chair-chair-boat conformation of the (S)-2,3-oxidosqualene precursor during the cyclization process, suggesting that the lupeol synthase from P. andrieuxii is of the same type as that from Olea europea and Taraxacum officinale, but different from that of Arabidopsis thaliana. The study shows that (13)CO2 pulse-chase experiments are powerful in elucidating, under in vivo conditions and in a single experiment, the biosynthesis of complex plant products including higher terpenes.

Natural folates from biofortified tomato and synthetic 5-methyl-tetrahydrofolate display equivalent bioavailability in a murine model.

Folate deficiency is a global health problem related to neural tube defects, cardiovascular disease, dementia, and cancer. Considering that folic acid (FA) supply through industrialized foods is the most successful intervention, limitations exist for its complete implementation worldwide. Biofortification of plant foods, on the other hand, could be implemented in poor areas as a complementary alternative. A biofortified tomato fruit that accumulates high levels of folates was previously developed. In this study, we evaluated short-term folate bioavailability in rats infused with this folate-biofortified fruit. Fruit from tomato segregants hyperaccumulated folates during an extended ripening period, ultimately containing 3.7-fold the recommended dietary allowance in a 100-g portion. Folate-depleted Wistar rats separated in three groups received a single dose of 1 nmol of folate/g body weight in the form of lyophilized biofortified tomato fruit, FA, or synthetic 5-CH3-THF. Folate bioavailability from the biofortified tomato was comparable to that of synthetic 5-CH3-THF, with areas under the curve (AUC(0-∞)) of 2,080 ± 420 and 2,700 ± 220 pmol · h/mL, respectively (P = 0.12). Whereas, FA was less bioavailable with an AUC(0-∞) of 750 ± 10 pmol · h/mL. Fruit-supplemented animals reached maximum levels of circulating folate in plasma at 2 h after administration with a subsequent steady decline, while animals treated with FA and synthetic 5-CH3-THF reached maximum levels at 1 h. Pharmacokinetic parameters revealed that biofortified tomato had slower intestinal absorption than synthetic folate forms. This is the first study that demonstrates the bioavailability of folates from a biofortified plant food, showing its potential to improve folate deficiency.

Biomedical applications of synthetic peptides derived from venom of animal origin: A systematic review.

Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of ß-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.

Sleep Disturbances and Mental Well-Being of Preschool Children during the COVID-19 Pandemic in Mexico.

COVID-19 pandemic confinement caused changes in families and children's routines worldwide. Studies conducted at the beginning of the pandemic have examined the harmful effects of these changes on mental health, including sleep disturbances. As sleep is essential for optimal childhood development, this study was designed to determine preschool-aged (3-6 years old) children's sleep parameters and mental well-being during the COVID-19 pandemic in Mexico. Using a cross-sectional design, a survey was applied to parents of preschool children, inquiring about their children's confinement status, routine changes, and electronics use. The parents responded to the Children's Sleep Habits Questionnaire and the Strengths and Difficulties Questionnaire to assess children's sleep and mental well-being. To provide objective sleep data, the children wore wrist actigraphy for seven days. Fifty-one participants completed the assessment. The children's mean age was 5.2 years, and the prevalence of sleep disturbances was 68.6%. The use of electronic tablets in the bedroom near bedtime and symptoms of mental health deterioration (i.e., emotional distress and behavioral difficulties) were associated with sleep disturbances and their severity. The COVID-19 pandemic's confinement-related routine changes greatly impacted preschool children's sleep and well-being. We recommend establishing age-tailored interventions to manage children at higher risk.

Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine.

BACKGROUND: The generation of induced pluripotent stem cells has opened the field of study for stem cell research, disease modeling and drug development. However, the epigenetic signatures present in somatic cells make cell reprogramming still an inefficient process. This epigenetic memory constitutes an obstacle in cellular reprogramming. Here, we report the effect of hydralazine (HYD) and valproic acid (VPA), two small molecules with proven epigenetic activity, on the expression of pluripotency genes in adult (aHF) and neonatal (nbHF) human fibroblasts. METHODS: aHF and nbHF were treated with HYD and/or VPA, and viability and gene expression assays for OCT4, NANOG, c-MYC, KLF4, DNMT1, TET3, ARID1A and ARID2 by quantitative PCR were performed. aHF and nbHF were transfected with episomal plasmid bearing Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and exposed to HYD and VPA to determine the reprogramming efficiency. Methylation sensitive restriction enzyme (MSRE) qPCR assays were performed on OCT4 and NANOG promoter regions. Immunofluorescence assays were carried out for pluripotency genes on iPSC derived from aHF and nbHF. RESULTS: HYD upregulated the expression of OCT4 (2.5-fold) and NANOG (fourfold) genes but not c-Myc or KLF4 in aHF and had no significant effect on the expression of all these genes in nbHF. VPA upregulated the expression of NANOG (twofold) in aHF and c-MYC in nbHF, while it downregulated the expression of NANOG in nbHF. The combination of HYD and VPA canceled the OCT4 and NANOG overexpression induced by HYD in aHF, while it reinforced the effects of VPA on c-Myc expression in nbHF. The HYD-induced overexpression of OCT4 and NANOG in aHDF was not dependent on demethylation of gene promoters, and no changes in the reprogramming efficiency were observed in both cell populations despite the downregulation of epigenetic genes DNMT1, ARID1A, and ARID2 in nbHF. CONCLUSIONS: Our data provide evidence that HYD regulates the expression of OCT4 and NANOG pluripotency genes as well as ARID1A and ARID2 genes, two members of the SWI/SNF chromatin remodeling complex family, in normal human dermal fibroblasts.

Mental health outcomes and risk factors among female physicians during the COVID-19 pandemic.

The fast spread of the COVID-19 pandemic brought a huge workload burden. Health care workers have become a particular risk group for developing mental health symptoms, with women being the most affected group according to preliminary data. The aim of this study was to provide information about the prevalence of depression, anxiety, sleep disturbances, and post-traumatic stress disorder symptoms in female physicians during the COVID-19 pandemic and describe risk factors associated with them. Using a cross-sectional design, we applied an online questionnaire to 303 female physicians inquiring about COVID-19 changes in their social and professional dynamics. To assess the presence of depression, anxiety, sleep disturbances, and post-traumatic stress disorder symptoms, the participants responded the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the Pittsburgh Sleep Quality Index (PSQI), and the PTSD Checklist for DSM-5 (PCL-5). The prevalence for depression, anxiety, sleep quality disturbances and PTSD symptoms was 72.6%, 64.3%, 77.8%, and 19.4% respectively. The main risk factor associated with every outcome was having a previous history of any mental health disorder. Younger age and being at the frontline for COVID-19 attention were relevant to depression symptoms. Our results were in agreement with previous studies, confirming the need for specific age-tailored mental health interventions in female physicians, especially those with previous diagnoses of mental health disorders.