PHF6 loss reduces leukemia stem cell activity in an acute myeloid leukemia mouse model.

Acute myeloid leukemia (AML) is a malignant hematologic disease caused by gene mutations and genomic rearrangements in hematologic progenitors. The PHF6 (PHD finger protein 6) gene is highly conserved and located on the X chromosome in humans and mice. We found that PHF6 was highly expressed in AML cells with MLL rearrangement and was related to the shortened survival time of AML patients. In our study, we knocked out the Phf6 gene at different disease stages in the AML mice model. Moreover, we knocked down PHF6 by shRNA in two AML cell lines and examined the cell growth, apoptosis, and cell cycle. We found that PHF6 deletion significantly inhibited the proliferation of leukemic cells and prolonged the survival time of AML mice. Interestingly, the deletion of PHF6 at a later stage of the disease displayed a better anti-leukemia effect. The expressions of genes related to cell differentiation were increased, while genes that inhibit cell differentiation were decreased with PHF6 knockout. It is very important to analyze the maintenance role of PHF6 in AML, which is different from its tumor-suppressing function in T-cell acute lymphoblastic leukemia (T-ALL). Our study showed that inhibiting PHF6 expression may be a potential therapeutic strategy targeting AML patients.

Preparation of liquid silicon-based carbon dots and application for luminescent solar concentrators.

Liquid silicon-based carbon dots (CDs) with a photoluminescence quantum yield (PLQY) of 50% were prepared using N-[3-(trimethoxysilyl)propyl]ethylenediamine (DAMO), citric acid, and n-butylamine as raw materials. Firstly, the optimized characters have been determined, namely, the optimal DAMO, citric acid, and n-butylamine addition amounts of 1 mL, 0.9 g, and 1 mL, a reaction time of 3 h, and a reaction temperature of 160°C. Further research has confirmed that the increase in fluorescence intensity of CDs is mainly due to the introduction of DAMO, in which the two amino groups in DAMO play a major role. In addition, the Si-O-Si group generated by the hydrolysis of siloxane groups is connected to the surface of the CDs and forms a core-shell structure, which modifies the defects on the surface and enhances the fluorescence intensity of the CDs. Finally, luminescent solar concentrators (LSCs) based on liquid silicon-based CDs were assembled by spin coating. The obtained device has a transparency of up to 80% and an optical efficiency of 2.4%.

Persistence of Chronic Lymphocytic Leukemia Stem-like Populations under Simultaneous In Vitro Treatment with Curcumin, Fludarabine, and Ibrutinib: Implications for Therapy Resistance.

Leukemic stem cells (LSCs) possess similar characteristics to normal hematopoietic stem cells, including self-renewal capacity, quiescence, ability to initiate leukemia, and drug resistance. These cells play a significant role in leukemia relapse, persisting even after apparent remission. LSCs were first described in 1994 by Lapidot et al. Although they have been extensively studied in acute leukemia, more LSC research is still needed in chronic lymphocytic leukemia (CLL) to understand if reduced apoptosis in mature cells should still be considered as the major cause of this disease. Here, we provide new evidence suggesting the existence of stem-like cell populations in CLL, which may help to understand the disease as well as to develop effective treatments. In this study, we identified a potential leukemic stem cell subpopulation using the tetraploid CLL cell line I83. This subpopulation is characterized by diploid cells that were capable of generating the I83 tetraploid population. Furthermore, we adapted a novel flow cytometry analysis protocol to detect CLL subpopulations with stem cell properties in peripheral blood samples and primary cultures from CLL patients. These cells were identified by their co-expression of CD19 and CD5, characteristic markers of CLL cells. As previously described, increased alkaline phosphatase (ALP) activity is indicative of stemness and pluripotency. Moreover, we used this method to investigate the potential synergistic effect of curcumin in combination with fludarabine and ibrutinib to deplete this subpopulation. Our results confirmed the effectiveness of this ALP-based analysis protocol in detecting and monitoring leukemic stem-like cells in CLL. This analysis also identified limitations in eradicating these populations using in vitro testing. Furthermore, our findings demonstrated that curcumin significantly enhanced the effects of fludarabine and ibrutinib on the leukemic fraction, exhibiting synergistic effects (combination drug index, CDI 0.97 and 0.37, respectively). Our results lend support to the existence of potential stem-like populations in CLL cell lines, and to the idea that curcumin could serve as an effective adjuvant in therapies aimed at eliminating these populations and improving treatment efficacy.

Perfusion index to predict post spinal hypotension in lower segment caesarean section.

Background and Aims: It is important to predict and prevent post-spinal hypotension in lower segment cesarean section (LSCS). Peripheral vascular tone can be monitored as a perfusion index (PI) from a pulse oximeter. We aimed to study baseline PI as a predictor of post-spinal hypotension in LSCS. Material and Methods: Prospective observational study conducted in a tertiary care teaching public hospital on patients posted for elective LSCS under spinal anesthesia. Baseline PI and hypotension were compared. A receiver operating characteristic (ROC) curve was plotted and data were analyzed using SPSS version 20. Results: Among 90 females, 43 (47.8%) had a PI ≤3.5 and 47 (52.2%) had a PI >3.5. In the PI >3.5 group, 46 (97.9%) females had hypotension and required a high volume of IV fluids, and 29 (61.7%) required vasopressors, and the association with PI was statistically significant with Pearson's Chi-square values of 32.26 and 32.36, respectively (P = 0.001). In the ROC, the area under the curve (AUC) was 0.917, proving baseline PI >2.9 as an excellent classifier (P < 0.0001,95% confidence interval [CI] 0.840-0.965) and can predict hypotension with a sensitivity of 83.08% and specificity of 96.00%. Conclusion: Baseline PI >3.5 was associated with significant post-spinal hypotension and vasopressor administration in LSCS. We established baseline PI >2.9 can predict post-spinal hypotension with high sensitivity and specificity. PI is simple, quick, and non-invasive and can be used as a predictor for post-spinal hypotension in parturients undergoing LSCS so that prophylactic measures can be considered in at-risk patients for better maternal and fetal outcomes.

The Therapeutic Potential of a Strategy to Prevent Acute Myeloid Leukemia Stem Cell Reprogramming in Older Patients.

Acute myeloid leukemia (AML) is the most common and incurable leukemia subtype. Despite extensive research into the disease's intricate molecular mechanisms, effective treatments or expanded diagnostic or prognostic markers for AML have not yet been identified. The morphological, immunophenotypic, cytogenetic, biomolecular, and clinical characteristics of AML patients are extensive and complex. Leukemia stem cells (LSCs) consist of hematopoietic stem cells (HSCs) and cancer cells transformed by a complex, finely-tuned interaction that causes the complexity of AML. Microenvironmental regulation of LSCs dormancy and the diagnostic and therapeutic implications for identifying and targeting LSCs due to their significance in the pathogenesis of AML are discussed in this review. It is essential to perceive the relationship between the niche for LSCs and HSCs, which together cause the progression of AML. Notably, methylation is a well-known epigenetic change that is significant in AML, and our data also reveal that microRNAs are a unique factor for LSCs. Multiple-targeted approaches to reduce the risk of epigenetic factors, such as the administration of natural compounds for the elimination of local LSCs, may prevent potentially fatal relapses. Furthermore, the survival analysis of overlapping genes revealed that specific targets had significant effects on the survival and prognosis of patients. We predict that the multiple-targeted effects of herbal products on epigenetic modification are governed by different mechanisms in AML and could prevent potentially fatal relapses. Thus, these strategies can facilitate the incorporation of herbal medicine and natural compounds into the advanced drug discovery and development processes achievable with Network Pharmacology research.

Pathogenic Mechanisms in Acute Myeloid Leukemia.

OPINION STATEMENT: Acute myeloid leukemia (AML) is the most common form of leukemia in adults, leading to the highest number of annual leukemia-associated deaths in the USA. Although most AML patients initially enter remission following induction therapy, most eventually relapse, underscoring the unmet need for more effective therapies. In recent years, novel high-throughput sequencing techniques, and mouse and human models of disease have increased our understanding of the molecular mechanisms that lead to AML. Leukemogenic mechanisms can be broadly classified into two types-cell-intrinsic and cell-extrinsic. Cell-intrinsic mechanisms include an array of genetic and epigenetic alterations that lead to dysregulated gene expression and function in hematopoietic stem/progenitor cells, leading to their increased fitness and ultimately, malignant transformation. Extrinsic mechanisms include both hematopoietic and non-hematopoietic stromal components of the leukemic microenvironment that interact with pre-leukemic and leukemic clones to promote their survival, self-renewal, and/or resistance to therapy. Through the individual and concerted action of these factors, pre-leukemic clones acquire the changes necessary for leukemic transformation. In addition, following therapy, specific leukemic clones are selected for that eventually re-initiate disease. Improving our understanding of these cell-intrinsic and cell-extrinsic mechanisms will provide novel opportunities to treat AML as well as prevent the development of disease.

Efficacy of ondansetron and palonosetron in prevention of shivering under spinal anesthesia: A prospective randomized double-blind study in patients undergoing elective LSCS.

BACKGROUND AND AIMS: Postanesthesia shivering (PAS) is a common, distressing experience. Ondansetron, the classical 5HT3 antagonist has been in use for its prevention since long. Palonosetron, a newly introduced potent antiemetic drug with better pharmacodynamics is currently in use by clinicians. Hence, a study was conducted to compare the efficacy of ondansetron and palonosetron in preventing PAS in patients undergoing elective lower segment caesarean section (LSCS) under spinal anaesthesia. MATERIAL AND METHODS: A total of 84 patients scheduled for elective LSCS under spinal anesthesia were randomly allocated to one of the two study groups (Group O & P). Accordingly, 8 mg of ondansetron or 0.075 mg palonosetron was administered in the same volume intravenously 30 min preoperatively. Sublingual temperature was recorded regularly. All patients were observed for 90 min postspinal for PAS. Observations were analyzed statiscally. RESULTS: No statistically significant intergroup difference was observed in the duration of surgery, and sublingual temperature. However, statistically significant difference was recorded for PAS (23.8% in ondansetron group, 9.5% in palonosetron group). CONCLUSION: Prophylactic administration of palonosetron significantly reduced incidence of PAS compared to ondansetron. However, further studies with larger sample size and more heterogeneous groups are suggested.

Comparison of the time taken for subarachnoid block using ultrasound-guided method versus landmark technique for cesarean section - A randomized controlled study.

BACKGROUND AND AIMS: Spinal anesthesia is the regional technique preferred for cesarean section and is usually administered using the traditional landmark technique. Ultrasonography of the spine appears to be helpful in locating the puncture site and increasing the success rate. The primary objective of this study was to assess the use of ultrasonogram in locating the lumbar interspinous space for spinal anesthesia in laboring parturients brought for elective cesarean section. MATERIAL AND METHODS: Sixty parturients scheduled to undergo elective cesarean section under spinal anesthesia were included in this prospective randomized controlled trial, after obtaining the institutional ethical clearance. In Group I, 30 patients received spinal anesthesia by landmark technique and in Group II, 30 patients underwent ultrasound-guided spinal anesthesia. The statistical analysis was done using SPSS software version 17 (SPSS Inc., Chicago, Illinois, USA) for Microsoft windows. RESULTS: The time taken for spinal in Group I was longer than in Group II (62 ± 18s; 41 ± 11s; P = 0.0001). The number of attempts of needle insertion was significantly less in Group II (group I 1.86 ± 1.04: group II 1.06 ± 0.25). However, the total preparation time (28 8.30 ± 92 vs 804.73 ± 77; P = 0.0001) was more in the ultrasound-guided than in the landmark group. The patients had better satisfaction in group II. CONCLUSION: Preprocedural ultrasound is a useful tool for successful lumbar puncture in parturients as it minimizes the number of attempts of needle insertion and provides better patient satisfaction.

[Ginsenoside Rg_1 induces leukemia stem cell senescence via SIRT1/TSC_2 signal axis].

The aim of this paper was to investigate the effect of SIRT1/TSC_2 signal axis on leukemia stem cell senescence induced by ginsenoside Rg_1. CD34~+CD38~- leukemia stem cells(CD34~+CD38~-LSCs) was isolated by magnetic cell sorting(MACS) and divided into two groups. The control group cells were routinely cultured, 40 µmol·L~(-1) ginsenoside Rg_1 was added to the control group for co-culture in Rg_1 group. The effect of Rg_l to induce CD34~+CD38~-LSCs senescence were evaluated by senescence-associated ß-Galactosidase(SA-ß-Gal) staining, cell cycle assay, CCK-8 and Colony-Assay. The expression of senescence associated SIRT1, TSC_2 mRNA and protein was examined by Real-time fluorescence quantitative PCR(FQ-PCR) and Western blot. The results showed that the CD34~+CD38~-LSCs could effectively be isolated by MACS, and the purity of CD34~+CD38~-LSCs is up to(95.86±3.04)%. Compared with the control group, the percentage of positive cells expressed SA-ß-Gal in the Rg_1 group is increased, the senescence morphological changes were observed in the CD34~+CD38~-LSCs in the Rg_1 group. The proliferation inhibition rate and the number of cells entered G_0/G_1 phase in the Rg_1 group were increased, but the colony-formed ability was decreased, Rg_1 could significantly inhibit the proliferation and self-renewal ability of CD34~+CD38~-LSCs. The expression of SIRT1 and TSC_2 mRNA and protein were down regulated in the Rg_1 group compared with the control group. Our research implied that Rg_1 may induce the senescence of CD34~+CD38~-LSCs and SIRT1/TSC_2 signal axis plays a significant role in this process.

Design, synthesis and evaluation of anti-CD123 antibody drug conjugates.

Leukemia stem cells (LSCs) account for the development of drug resistance and increased recurrence rate in acute myeloid leukemia (AML) patients. Targeted drug delivery to leukemia stem cells remains a major challenge in AML chemotherapy. Overexpressed interleukin-3 receptor alpha chain, CD123, on the surface of leukemia stem cells was reported to be a potential target in AML treatment. Here, we designed and developed an antibody drug conjugate (CD123-CPT) by integrating anti-CD123 antibody with a chemotherapeutic agent, Camptothecin (CPT), via a disulfide linker. The linker is biodegradable in the presence of Glutathione (GSH, an endogenous component in cells), which leads to release of CPT. Anti-CD123 antibody conjugates showed significant higher cellular uptake in CD123-overexpressed tumor cells. More importantly, CD123-CPT demonstrated potent inhibitory effects on CD123-overexpressed tumor cells. Consequently, these results provide a promising targeted chemotherapeutical strategy for AML treatment.

Phosphoinositide-dependent kinase 1 regulates leukemia stem cell maintenance in MLL-AF9-induced murine acute myeloid leukemia.

Although great efforts have been made to improve available therapies, the mortality rate of acute myeloid leukemia (AML) remains high due to poor treatment response and frequent relapse after chemotherapy. Leukemia stem cells (LSCs) are thought to account for this poor prognosis and relapse. Phosphoinositide-dependent kinase 1 (PDK1) is a critical regulator of the PI3K/Akt pathway and has been shown to be frequently activated in leukemia. However, the role of PDK1 in the regulation of LSCs in AML is still not clear. Using a PDK1 conditional deletion MLL-AF9 murine AML model, we revealed that the deletion of PDK1 prolonged the survival of AML mice by inducing LSC apoptosis. This was accompanied by the increased expression of the pro-apoptotic genes Bax and p53 and the reduced expression of Stat5, which has been shown to be constitutively activated in leukemia. Thus, our findings suggest that PDK1 plays an essential role in maintaining LSCs. Further delineating the function of PDK1 in LSCs may provide a new strategy for the improved treatment of AML relapse.

MEIS inhibitors reduce the viability of primary leukemia cells and Stem cells by inducing apoptosis.

Leukemia stem cells (LSCs) exhibit self-renewal, resistance to standard treatments, and involvement in leukemia relapse. Higher Myeloid Ecotropic Integration Site-1 (MEIS1) expression in leukemic blast samples has been linked to resistance to conventional treatment. We studied the MEIS1 and associated factors in relapsed LSCs and assessed the effect of recently developed MEIS inhibitors (MEISi). Meis1 gene expression was found to be higher in patients with leukemia and relapsed samples. The majority of CD123+ and CD34+ LSCs demonstrated higher MEIS1/2/3 content. Depending on the patient chemotherapy regimen, Meis1 expression increased in relapsed samples. Although there are increased Meis2, Meis3, Hoxa9, Pbx1, or CD34 expressions in the relapsed patients, they are not correlated with Meis1 content in every patient or regimen. MEISi has reduced MEIS1 transcriptional activity and LSC cell survival by apoptosis. Pharmacological targeting with MEISi in LSCs could have a potential effect in limiting leukemia relapse and chemotherapeutic resistance.

Intracranial hypotension with subdural hematoma after spinal anesthesia in obstetric patient: A rare but fatal complication.

Intracranial bleed in the form of subdural hematoma (SDH) with intracranial hypotension after spinal anesthesia for cesarean section is a rare condition with an incidence of around 1 in 5,00,000 obstetric populations. As its presentation is similar to post-dural puncture headache (PDPH), it can be misdiagnosed sometimes. Persistent headache for more than 5 days, vomiting, blurring of vision, and convulsion can guide the diagnosis of intracranial bleed. Magnetic resonance imaging (MRI) helps to diagnose the location, size, and other abnormalities of bleed in such patients. The management ranges from conservative to surgical management in the form of craniotomy. Here, we present a case of a 19-year-old woman, who operated on for cesarean section under spinal anesthesia presented with SDH and intracranial hypotension on postoperative day (POD) 6. She was managed conservatively with plenty of intravenous (IV) fluids, bed rest, low head position, analgesics, and antiepileptics. A repeat computed tomography (CT) scan was performed after 14 days, which showed resolved SDH, and the patient was discharged.

Anesthetic Challenges Associated With Posterior Reversible Encephalopathy Syndrome in a Pregnant Woman Scheduled for a Caesarean Section.

Recently, there has been a rise in reports of posterior reversible encephalopathy syndrome (PRES), which is an uncommon neurologic illness. The precise cause of PRES syndrome is yet unknown, but there are certain illnesses that have been associated with it. Furthermore, because of advances in imaging methods and growing awareness, the connection between PRES and pre-eclampsia/eclampsia is becoming increasingly recognised. Pre-eclampsia/eclampsia by itself poses distinct perioperative difficulties; in addition, PRES makes anesthesia administration more difficult. Regretfully, there is a lack of knowledge regarding the anesthetic treatment provided to the extremely sick and medically complex patients, and it is uncertain whether the chosen anesthetic might exacerbate neurologic problems. Here, we discuss the implications for the anesthetic management of PRES presentations.

The diagnostic accuracy of preoperative perfusion index as a predictor of postspinal anesthesia hypotension in parturients undergoing cesarean delivery: A prospective non-blinded observational study.

Background and Objectives: Spinal anesthesia is the technique of choice for elective cesarean section with a prominent side effect of postspinal anesthesia hypotension (PSH). This needs an early prediction to avoid feto-maternal complication. This study aimed to assess the diagnostic accuracy of perfusion index (PI) and inferior vena cava collapsibility index (IVCCI) in the prediction of PSH. Material and Methods: Thirty parturients of American Society of Anesthesiologists Physical Status (ASA-PS) 1 and two undergoing cesarean delivery participated in the study. IVCCI, PI, baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and heart rate (HR) were noted in the preoperative period. The fall of MBP by 20% from baseline or below 65 mm Hg was considered PSH. After spinal anesthesia, SBP, DBP, MBP, and HR were noted again for diagnosing PSH. Results: It did not show any statistical difference when comparing the PI between the PSH and non-PSH groups in both the PSH definition groups. IVCCI was significantly higher when PSH was considered MBP <65 mm Hg (P = 0.01). However, IVCCI was found to be statistically insignificant if PSH was considered a 20% reduction in baseline MBP. The correlation matrix between IVCCI and PI showed Pearson's r-value of 0.525, indicating a substantial relationship between the two (P = 0.003). Multivariate logistic regression analysis had shown that neither IVCCI nor PI was a good predictor of PSH in parturients for both definition groups for PSH. Conclusion: Although there is a modest correlation between PI and IVCCI, both cannot be used to predict postspinal hypotension in parturients undergoing elective lower-segment cesarean section (LSCS).

A Comprehensive Case Report Emphasizing the Role of Caesarean Section, Antibiotic Prophylaxis, and Post-operative Care in Meconium-Stained Fetal Distress Syndrome.

Meconium-stained amniotic fluid (MSAF) presents a complex medical scenario with significant implications for maternal and neonatal health. This case report explores the intricacies surrounding MSAF, focusing on its diagnosis, treatment, and the associated meconium aspiration syndrome (MAS). The report emphasizes the critical role of antibiotic prophylaxis in lower segment cesarean sections (LSCS) in balancing infection prevention in the mother with neonatal considerations. Additionally, it highlights personalized pain management and post-operative care regimens, contributing to a comprehensive strategy for maternal and neonatal well-being. A 27-year-old primigravida (primi) underwent a cesarean section due to the presence of meconium in the amniotic fluid, indicating fetal distress. The report meticulously documents vital signs, laboratory findings, and the timeline of events. The case report underscores the importance of diagnosing and treating MAS, offering valuable insights into management strategies and their impact on maternal and neonatal health. This case report emphasizes the critical role of antibiotic prophylaxis in LSCS to prevent maternal infection while considering neonatal well-being. The personalized pain management approach and post-operative care regimens contribute significantly to a comprehensive strategy for maternal and neonatal well-being. The findings provide valuable insights into diagnosing and treating MAS, highlighting the importance of timely intervention in similar clinical scenarios.

Incidence of post-dural lumbar puncture headache (PDLPH) in comparison between emergency and elective lower segment cesarean section (LSCS) with 26G Quincke-Babcock cutting-beveled spinal needle.

Background: C-section is usually performed under spinal anesthesia also known as a subarachnoid block (SAB) over general anesthesia. Because of the lesser amount of dose used, there is a lower risk of local anesthetic toxicity and minimal transfer of drugs to the fetus. Obstetric patients have a higher risk of having post-dural puncture headache (PDPH). PDPH occurs due to leakage of the cerebrospinal fluid (CSF) through the hole created by a spinal needle. There are many elements affecting the frequency of PDPH, these elements can also consist of age, female sex, needle size, and types, pregnancy, preceding records of PDPH, median-paramedian distinction in approach, a puncture level. PDPH is commonly in the form of a frontal, occipital, or retro-orbital headache that starts in 12-72 h after the dural puncture and will increase when standing and decrease when lying down or resting. We aimed to learn about headache frequency between elective and emergency lower segment cesarean section using 26-G Quincke spinal needle in full-term pregnant patients. Objectives: To study the incidence of PDPH using the 26G Quincke spinal needle. To analyze the causal factors/determinants such as adequate preloading of fluids, size of spinal needle, number of pricks, and technique of lumbar puncture effects on the incidence of PDPH. Methodology: This study is a prospective questionnaire-based comparative observational study using the convenience sampling method. The patients were interviewed with a structured questionnaire at the Symbiosis University Hospital and Research Centre, Lavale, Pune. The patients observed for the study were between 20 and 40 of age group, posted for emergency or elective lower segment cesarean section, with body mass index (BMI) less than 14.5 to 24.9 and with ASA I and II grades. Patients with any comorbidities, recurrent headaches, obesity, and spine deformity were excluded. According to the review of the literature and with the help of a formula, the sample size was calculated as 20; 10 patients for elective LSCS, and 10 patients for emergency LSCS. Results: Out of 20 patients, 10 patients were posted for elective LSCS, and the rest 10 patients were for emergency LSCS under spinal anesthesia. The incidence of PDPH was found only in 2 out of 10 emergency LSCS patients, and no patients from elective LSCS cases showed up with the incidence of PDPH.

Senescence Promotes the Recovery of Stemness among Cancer Cells via Reprograming.

Both the senescence of cancer cells and the maintenance of cancer stem cells seem to be mutually exclusive because senescence is considered a physiological mechanism that effectively suppresses tumor growth. Recent studies have revealed common signaling pathways between cellular senescence and the maintenance of stemness in cancer cells, thus challenging the conventional understanding of this process. Although the links between these processes have not yet been fully elucidated, emerging evidence indicates that senescent cancer cells can undergo reprograming to recover stemness. Herein, we provide a comprehensive overview of the close correlation between senescence and stemness reprograming in cancer cells, with a particular focus on the mechanisms by which senescent cancer cells recover their stemness in various tumor systems.

The Reliability of PCL/Anti-VEGF Electrospun Scaffolds to Support Limbal Stem Cells for Corneal Repair.

Since only few reported studies propose anti-vascular endothelial growth factor (anti-VEGF) delivery through electrospun scaffolds, this study greatly contributes to the potential prevention of patient's vision loss, as it explores electrospun polycaprolactone (PCL) coated with anti-VEGF for the blockage of abnormal cornea vascularization. In terms of physicochemical properties, the biological component increased the PCL scaffold fiber diameter (by ~24%) and pore area (by ~82%), while ut slightly reduced its total porosity as the anti-VEGF solution filled the voids of the microfibrous structure. The addition of the anti-VEGF increased the scaffold stiffness almost three-fold at both strains of 5 and 10%, as well as its biodegradation rate (~36% after 60 days) with a sustained release profile after Day 4 of phosphate buffered saline incubation. In terms of scaffold application function, the PCL/Anti-VEGF scaffold proved to be more favorable for the adhesion of cultured limbal stem cells (LSCs); this was confirmed by the SEM images, where the cells showed flat and elongated conformations. Further support of the LSC growth and proliferation was confirmed by the identified p63 and CK3 markers after cell staining. These results demonstrate the advantageous effect of the surface-adsorbed anti-VEGF to stop vision loss and help damaged corneal tissue repair.

Understanding the Wnt Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Feasible Key against Relapses.

Wnt signaling is a highly conserved pathway in evolution which controls important processes such as cell proliferation, differentiation and migration, both in the embryo and in the adult. Dysregulation of this pathway can favor the development of different types of cancer, such as acute myeloid leukemia and other hematological malignancies. Overactivation of this pathway may promote the transformation of pre-leukemic stem cells into acute myeloid leukemia stem cells, as well as the maintenance of their quiescent state, which confers them with self-renewal and chemoresistance capacity, favoring relapse of the disease. Although this pathway participates in the regulation of normal hematopoiesis, its requirements seem to be greater in the leukemic stem cell population. In this review, we explore the possible therapeutic targeting of Wnt to eradicate the LSCs of AML.