Twin pregnancy with incomplete hydatidiform mole and coexistent normal live fetus: A case report and review of the literature.

RATIONALE: A pregnancy with incomplete mole is very rare case. Hydatidiform mole (HM) with live fetus is associated with a risk of a wide variety to maternal and fetal complications. The incidence of a normal live fetus and an incomplete mole such as the case we describe is extremely rare. PATIENT CONCERN: We report a case of multiparous 34-year-old at Culiacan Mexico woman with incomplete mole coexisting with normal fetus, pregnant 35.3 weeks who presented anemia grade II. DIAGNOSIS: The initial diagnosis of the mole was by ultrasound. INTERVENTIONS: KERR-type cesarean section and bilateral tubal occlusion. The newborn was morphologically normal, and she did not require intervention or treatment. OUTCOMES: The newborn was feminine, morphologically normal, weighing 2380 g and 47 cm, APGAR score 8 to 9, delivered prematurely, and there was a large placental plate. The blood loss on surgery was estimated at 1000 mL. Histopathology report of an incomplete hydatidiform mole, negative for malignancy. Histopathology diagnostic was confirmed by immunohistochemistry staining for p57KIP2. LESSONS: Although the incidence of this pregnancy is very rare, early recognition, diagnosis and divulge of the cases of medical community is very important for patient care.

The Role of ncRNAs in the Immune Dysregulation of Preeclampsia.

The main complications causing practically 75% of all maternal deaths are severe bleeding, infections, and high blood pressure during pregnancy (preeclampsia (PE) and eclampsia). The usefulness of ncRNAs as clinical biomarkers has been explored in an extensive range of human diseases including pregnancy-related diseases such as PE. Immunological dysregulation show that the Th1/17:Th2/Treg ratio is "central and causal" to PE. However, there is evidence of the involvement of placenta-expressed miRNAs and lncRNAs in the immunological regulation of crucial processes of placenta development and function during pregnancy. Abnormal expression of these molecules is related to immune physiopathological processes that occur in PE. Therefore, this work aims to describe the importance of miRNAs and lncRNAs in immune dysregulation in PE. Interestingly, multiple ncRNAS are involved in the immune dysregulation of PE participating in type 1 immune response regulation, immune microenvironment regulation in placenta promoting inflammatory factors, trophoblast cell invasion in women with Early-Onset PE (EOPE), placental development, and angiogenesis, promotion of population of M1 and M2, proliferation, invasion, and migration of placental trophoblast cells, and promotion of invasion and autophagy through vias such as PI3K/AKT/mTOR, VEGF/VEGFR1, and TLR9/STAT3.

SOX9 knockout decreases stemness properties in colorectal cancer cells.

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. SRY-box transcription factor 9 (SOX9) participates in organogenesis and cell differentiation in normal tissues but has been involved in carcinogenesis development. Cancer stem cells (CSCs) are a small population of cells present in solid tumors that contribute to increased tumor heterogeneity, metastasis, chemoresistance, and relapse. CSCs have properties such as self-renewal and differentiation, which can be modulated by many factors. Currently, the role of SOX9 in the maintenance of the stem phenotype has not been well elucidated, thus, in this work we evaluated the effect of the absence of SOX9 in the stem phenotype of CRC cells. Methods: We knockout (KO) SOX9 in the undifferentiated CRC cell line HCT116 and evaluated their stemness properties using sphere formation assay, differentiation assay, and immunophenotyping. Results: SOX9-KO affected the epithelial morphology of HCT116 cells and stemness characteristics such as its pluripotency signature with the increase of SOX2 as a compensatory mechanism to induce SOX9 expression, the increase of KLF4 as a differentiation feature, as well as the inhibition of the stem cell markers CD44 and CD73. In addition, SOX9-KO cells gain the epithelial-mesenchymal transition (EMT) phenotype with a significant upregulation of CDH2. Furthermore, our results showed a remarkable effect on first- and second-sphere formation, being SOX9-KO cells less capable of forming high-size-resistant spheres. Nevertheless, CSCs surface markers were not affected during the differentiation assay. Conclusions: Collectively, our findings supply evidence that SOX9 promotes the maintenance of stemness properties in CRC-CSCs.

National sex- and age-specific burden of blindness and vision impairment by cause in Mexico in 2019: a secondary analysis of the Global Burden of Disease Study 2019.

Background: Reliable national estimations for blindness and vision impairment are fundamental to assessing their burden and developing public health policies. However, no comprehensive analysis is available for Mexico. Therefore, in this observational study we describe the national burden of blindness and vision loss by cause and severity during 2019. Methods: Using public data from the Global Burden of Disease (GBD) study 2019, we present national prevalence and years lived with disability (YLDs) counts and crude and age-standardized rates (per 100,000 people) of total, severity- and cause-specific blindness and vision impairment with 95% uncertainty intervals (UIs) by sex and age group. Findings: In Mexico, the burden of blindness and vision impairment was estimated at 11.01 million (95% UI, 9.25-13.11) prevalent cases and 384.96 thousand (259.57-544.24) YLDs during 2019. Uncorrected presbyopia caused the highest burden (6.06 million cases, 4.36-8.08), whereas severe vision loss and blindness affected 619.40 thousand (539.40-717.73) and 513.84 thousand (450.59-570.98) people, respectively. Near vision loss and refraction disorders caused 78.7% of the cases, whereas neonatal disorders and age-related macular degeneration were among the least frequent. Refraction disorders were the main cause of moderate and severe vision loss (61.44 and 35.43%), and cataracts were the second most frequent cause of blindness (26.73%). Females suffered an overall higher burden of blindness and vision impairment (54.99% and 52.85% of the total cases and YLDs), and people >50 years of age suffered the highest burden, with people between 70 and 74 years being the most affected. Interpretation: Vision loss represents a public health problem in Mexico, with women and older people being the most affected. Although the causes of vision loss contribute differentially to the severity of visual impairment, most of the impairment is avoidable. Consequently, a concerted effort at different levels is needed to alleviate this burden. Funding: This study received no funding.

National Burden and Trends for 29 Groups of Cancer in Mexico from 1990 to 2019: A Secondary Analysis of the Global Burden of Disease Study 2019.

The global burden of cancer is on the rise, with varying national patterns. To gain a better understanding and control of cancer, it is essential to provide national estimates. Therefore, we present a comparative description of cancer incidence and mortality rates in Mexico from 1990 to 2019, by age and sex for 29 different cancer groups. Based on public data from the Global Burden of Disease Study 2019, we evaluated the national burden of cancer by analyzing counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and trends using the annual percentage change from 1990 to 2019. In 2019, cancer resulted in 222,060 incident cases and 105,591 deaths. In 2019, the highest incidence of cancer was observed in non-melanoma skin cancer, prostate cancer, and breast cancer. Additionally, 53% of deaths were attributed to six cancer groups (lung, colorectal, stomach, prostate, breast, and pancreatic). From 1990 to 2019, there was an increasing trend in incidence and mortality rates, which varied by 10-436% among cancer groups. Furthermore, there were cancer-specific sex differences in crude and age-standardized rates. The results show an increase in the national cancer burden with sex-specific patterns of change. These findings can guide national efforts to reduce health loss due to cancer.

Extracellular matrix hydrogel derived from bovine bone is biocompatible in vitro and in vivo.

BACKGROUND: Nowadays, biomaterials used as a scaffold must be easy to deliver in the bone defect area. Extracellular matrix (ECM) hydrogels are highly hydrated polymers that can fill irregular shapes and act as bioactive materials. OBJECTIVE: This work aims to show the effects of ECM hydrogels derived from bovine bone (bECMh) on proliferation, cytotoxicity and expression of pro-inflammatory cytokines in three cells types involved in tissue regeneration, as well as biocompatibility in vivo. METHODS: In vitro, we used an extract of bECMh to test it on macrophages, fibroblasts, and adipose-derived mesenchymal stem cells (AD-MCSs). Cell proliferation was measured using the MTT assay, cytotoxicity was measured by quantifying lactate dehydrogenase release and the Live/Dead Cell Imaging assays. Concentrations of IL-6, IL-10, IL-12p70, MCP-1 and TNF-α were quantified in the supernatants using a microsphere-based cytometric bead array. For in vivo analysis, Wistar rats were inoculated into the dorsal sub-dermis with bECMh, taking as reference the midline of the back. The specimens were sacrificed at 24 h for histological study. RESULTS: In vitro, this hydrogel behaves as a dynamic biomaterial that increases fibroblast proliferation, induces the production of pro-inflammatory cytokines in macrophages, among which MCP-1 and TNF-α stand out. In vivo, bECMh allows the colonization of host fibroblast-like and polymorphonuclear cells, without tissue damage or inflammation. CONCLUSIONS: The results indicate that bECMh is a biocompatible material that could be used as a scaffold, alone or in conjunction with cells or functional biomolecules, enhancing proliferation and allowing the filling of bone defects to its further regeneration.

Lack of Effects of the Genetic Polymorphisms of Interleukin-10 in Clinical Outcomes of COVID-19.

Interleukin-10 (IL-10) gene polymorphisms have been associated with severity and outcomes in patients with respiratory and nonrespiratory viral infections. The aim of this study was to assess whether rs1800871 and rs1800872 polymorphisms of IL-10 gene are associated with the clinical outcomes of COVID-19 in a Mexican population. Study subjects were 193 COVID-19 patients. The genotyping was carried out with real-time PCR and serum IL-10 levels were measured with enzyme-linked immunosorbent assay. Logistic regression analysis was used for analysis association with clinical outcomes. There was no evidence of an association between alleles, genotypes, or haplotypes frequencies between patient groups according to severity and outcomes. The rs1800871 and rs1800872 polymorphisms might not be genetic risk factors for severity and mortality for COVID-19 in Mexican mestizos patients from northwest Mexico.

SOX9 is associated with advanced T-stages of clinical stage II colon cancer in young Mexican patients.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and includes colon cancer (CC) and rectal cancer (RC). Regarding CC, the development of novel molecular biomarkers for the accurate diagnosis and prognosis, as well as the identification of novel targets for therapeutic intervention, are urgently needed. SRY-related high-mobility group box 9 (SOX9), a transcription factor, is involved in development, and has been associated with the progression of human cancer. However, its underlying clinical and functional effects in CRC have not been fully understood. Therefore, the present study aimed to evaluate the clinical and functional relevance of SOX9 expression in CC. The expression of SOX9 in tumor tissues was evaluated in 97 biopsies from Mexican patients with CC with early-stage I and II disease by immunohistochemistry (IHC). In addition, SOX9 silencing in the HCT116 cell line was performed using specific small interfering RNAs, while downregulation efficiency was verified by reverse transcription-quantitative PCR and immunofluorescence. Spheroid-formation assay was carried out using ultra-low attachment plates. The IHC results showed that SOX9 was upregulated in patients with stage II (91%) and advanced T3 stage (67%) CC. Interestingly, higher SOX9 expression was associated with clinical stage, tumor size and tumor location. Furthermore, increased SOX9 expression was found in relapsed cases with local tumors; however, it was not associated with increased survival probability. Additionally, functional analysis indicated that SOX9 silencing significantly attenuated the sphere-formation capability of HCT116 cells. The present study was the first to evaluate the expression levels of SOX9 in Mexican patients diagnosed with early-stage CC. The aforementioned findings indicated that high SOX9 expression could play an important role in tumorigenesis and be associated with advanced T-stages of clinical-stage II patients, but not with relapse-free survival.

Refocusing the Use of Psychiatric Drugs for Treatment of Gastrointestinal Cancers.

Gastrointestinal cancers (GICs) are the most common human tumors worldwide. Treatments have limited effects, and increasing global cancer burden makes it necessary to investigate alternative strategies such as drug repurposing. Interestingly, it has been found that psychiatric drugs (PDs) are promising as a new generation of cancer chemotherapies due to their anti-neoplastic properties. This review compiles the state of the art about how PDs have been redirected for cancer therapeutics in GICs. PDs, especially anti-psychotics, anti-depressants and anti-epileptic drugs, have shown effects on cell viability, cell growth, inhibition of proliferation (cell cycle arrest), apoptosis promotion by caspases activation or cytochrome C release, production of reactive oxygen species (ROS) and nuclear fragmentation over esophageal, gastric, colorectal, liver and pancreatic cancers. Additionally, PDs can inhibit neovascularization, invasion and metastasis in a dose-dependent manner. Moreover, they can induce chemosensibilization to 5-fluorouracil and cisplatin and can act synergistically with anti-neoplastic drugs such as gemcitabine, paclitaxel and oxaliplatin. All anti-cancer activities are given by activation or inhibition of pathways such as HDAC1/PTEN/Akt, EGFR/ErbB2/ErbB3, and PI3K/Akt; PI3K-AK-mTOR, HDAC1/PTEN/Akt; Wnt/ß-catenin. Further investigations and clinical trials are needed to elucidate all molecular mechanisms involved on anti-cancer activities as well as adverse effects on patients.

A novel protective role for microRNA-3135b in Golgi apparatus fragmentation induced by chemotherapy via GOLPH3/AKT1/mTOR axis in colorectal cancer cells.

Chemotherapy activates a novel cytoplasmic DNA damage response resulting in Golgi apparatus fragmentation and cancer cell survival. This mechanism is regulated by Golgi phosphoprotein-3 (GOLPH3)/Myo18A/F-actin axis. Analyzing the functions of miR-3135b, a small non-coding RNA with unknown functions, we found that its forced overexpression attenuates the Golgi apparatus fragmentation induced by chemotherapeutic drugs in colorectal cancer (CRC) cells. First, we found that miR-3135b is downregulated in CRC cell lines and clinical tumors. Bioinformatic predictions showed that miR-3135b could be regulating protein-encoding genes involved in cell survival, resistance to chemotherapy, and Golgi dynamics. In agreement, ectopic transfection of miR-3135b in HCT-15 cancer cells significantly inhibited cell proliferation, sensitized cells to 5-fluoruracil (5-FU), and promoted late apoptosis and necrosis. Also, miR-3135b overexpression impaired the cell cycle progression in HCT-15 and SW-480 cancer cells. Because GOLPH3, a gene involved in maintenance of Golgi structure, was predicted as a potential target of miR-3135b, we studied their functional relationships in response to DNA damage induced by chemotherapy. Immunofluorescence and cellular ultrastructure experiments using antibodies against TGN38 protein, a trans-Golgi network marker, showed that 5-FU and doxorubicin treatments result in an apoptosis-independent stacks dispersal of the Golgi ribbon structure in both HCT-15 and SW-480 cells. Remarkably, these cellular effects were dramatically hindered by transfection of miR-3135b mimics. In addition, our functional studies confirmed that miR-3135b binds to the 3'-UTR of GOLPH3 proto-oncogene, and also reduces the levels of p-AKT1 (Ser473) and p-mTOR (Ser2448) signaling transducers, which are key in cell survival and autophagy activation. Moreover, we found that after treatment with 5-FU, TGN38 factor coimmunolocalizes with beclin-1 autophagic protein in discrete structures associated with the fragmented Golgi, suggesting that the activation of pro-survival autophagy is linked to loss of Golgi integrity. These cellular effects in autophagy and Golgi dispersal were reversed by miR-3135b. In summary, we provided experimental evidence suggesting for the first time a novel role for miR-3135b in the protection of chemotherapy-induced Golgi fragmentation via GOLPH3/AKT1/mTOR axis and protective autophagy in colorectal cancer cells.

Cell Survival Is Regulated via SOX9/BCL2L1 Axis in HCT-116 Colorectal Cancer Cell Line.

Colorectal cancer (CRC) is one of the most frequent types of malignancies and one of the major causes of cancer-related death worldwide. Sex-determining region Y (SRY)-box 9 protein (SOX9) is a member of the SOX family of transcription factors which are involved in the regulation of differentiation and development. Recently, several reports suggest an important role of SOX9 in tumorigenesis since its overexpression correlates with tumor progression and poor outcome in several types of cancer; however, its role in CRC is not clear until now. Therefore, in this work, we searched for novel SOX9-regulated genes involved in cell survival of CRC. We silenced SOX9 in the poorly differentiated HCT-116 cell line, using a specific siRNA, to identify differential expressed genes by DNA microarrays and analyzed the role or candidate genes in apoptosis and autophagy. Transcriptome analysis showed that diverse cellular pathways, associated with CRC carcinogenesis such as Wnt/ß-catenin, MAPK, TGF-ß, and mTOR, were modulated after SOX9 silencing. Interestingly, we found that SOX9 silencing promotes downregulation of BCL2L1 and overexpression of CASP3, proteins related to apoptosis, which was further confirmed in SW-480, a moderated-differentiated cell line, but not in HT-29, well-differentiated cell line. Moreover, inhibition of BCL2L1 by ABT-737 (BH3 mimetic) in SOX9-silenced HCT-116 cells resulted in an increased apoptosis percentage. However, downregulation of BCL2L1 was not enough to induce autophagy. This is the first report, suggesting that cell survival in poorly and moderated-differentiated CRC cells lines is regulated by SOX9/BCL2L1 axis, but not in well-differentiated cell lines.

Cancer Stem Cells and Its Role in Angiogenesis and Vasculogenic Mimicry in Gastrointestinal Cancers.

Cancer stem cells (CSCs) are able to promote initiation, survival and maintenance of tumor growth and have been involved in gastrointestinal cancers (GICs) such as esophageal, gastric and colorectal. It is well known that blood supply facilitates cancer progression, recurrence, and metastasis. In this regard, tumor-induced angiogenesis begins with expression of pro-angiogenic molecules such as vascular endothelial growth factor (VEGF), which in turn lead to neovascularization and thus to tumor growth. Another pattern of blood supply is called vasculogenic mimicry (VM). It is a reminiscent of the embryonic vascular network and is carried out by CSCs that have the capability of transdifferentiate and form vascular-tube structures in absence of endothelial cells. In this review, we discuss the role of CSCs in angiogenesis and VM, since these mechanisms represent a source of tumor nutrition, oxygenation, metabolic interchange and facilitate metastasis. Identification of CSCs mechanisms involved in angiogenesis and VM could help to address therapeutics for GICs.

LncRNAs as Regulators of Autophagy and Drug Resistance in Colorectal Cancer.

Colorectal cancer (CRC) is a common malignancy with 1. 8 million cases in 2018. Autophagy helps to maintain an adequate cancer microenvironment in order to provide nutritional supplement under adverse conditions such as starvation and hypoxia. Additionally, most of the cases of CRC are unresponsive to chemotherapy, representing a significant challenge for cancer therapy. Recently, autophagy induced by therapy has been shown as a unique mechanism of resistance to anticancer drugs. In this regard, long non-coding RNAs (lncRNAs) analysis are important for cancer detection, progression, diagnosis, therapy response, and prognostic values. With increasing development of quantitative detection techniques, lncRNAs derived from patients' non-invasive samples (i.e., blood, stools, and urine) has become into a novel approach in precision oncology. Tumorspecific GAS5, HOTAIR, H19, and MALAT are novels CRC related lncRNAs detected in patients. Nonetheless, the effect and mechanism of lncRNAs in cancer autophagy and chemoresistance have not been extensively characterized. Chemoresistance and autophagy are relevant for cancer treatment and lncRNAs play a pivotal role in resistance acquisition for several drugs. LncRNAs such as HAGLROS, KCNQ1OT1, and H19 are examples of lncRNAs related to chemoresistance leaded by autophagy. Finally, clinical implications of lncRNAs in CRC are relevant, since they have been associated with tumor differentiation, tumor size, histological grade, histological types, Dukes staging, degree of differentiation, lymph node metastasis, distant metastasis, recurrent free survival, and overall survival (OS).

SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer.

Transcriptional and epigenetic embryonic programs can be reactivated in cancer cells. As result, a specific subset of undifferentiated cells with stem-cells properties emerges and drives tumorigenesis. Recent findings have shown that ectoderm- and endoderm-derived tissues continue expressing stem-cells related transcription factors of the SOX-family of proteins such as SOX2 and SOX9 which have been implicated in the presence of cancer stem-like cells (CSCs) in tumors. Currently, there is enough evidence suggesting an oncogenic role for SOX9 in different types of human cancers. This review provides a summary of the current knowledge about the involvement of SOX9 in development and progression of cancer. Understanding the functional roles of SOX9 and clinical relevance is crucial for developing novel treatments targeting CSCs in cancer.