Quantitative measurement of CA 15-3 cancer biomarker using an electrochemical aptasensor based on the electrodeposition of Au thin film on cauliflower-like rGO-MoS2 nanocomposite.

The present research was conducted to design and construct an electrochemical aptasensor for evaluating carbohydrate antigen 15-3 (CA15-3) as a biomarker for breast cancer. The aptasensor has been fabricated by a gold thin film (AuTF) electrodeposited on a cauliflower-like reduced graphene oxide-molybdenum sulfide nanocomposite (rGO-MoS2). The modified electrode's surface was used to immobilize the thiolated aptamer, which was subsequently treated with CA 15-3 antigen. The aptasensor fabrication process was assessed using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). This research also applied EIS to the quantitative measurement of CA 15-3 antigen by the proposed aptasensor. The interfacial charge transfer resistance (Rct) alteration before and after incubation of CA 15-3 by the immobilized aptamer was considered a signal for the quantitative measurement of CA 15-3. A linear concentration ranging from 5.0 to 200.0 U mL-1 with a detection limit of 3.0 × 10-1 U mL-1 was obtained for CA 15-3 using the EIS method. This designed aptasensor indicates satisfactory repeatability and stability, good selectivity, and high sensitivity. Moreover, clinical samples were assayed by the prepared aptasensor and compared with the ELISA method, yielding acceptable results. The recovery and relative standard deviation (RSD) of CA 15-3 in human serum samples were in the range 95.0 to 107.0% and 3.5 to 7.5%, respectively.

Mechanism and antibacterial synergies of poly(Dabco-BBAC) nanoparticles against multi-drug resistant Pseudomonas aeruginosa isolates from human burns.

Multi-drug resistant bacteria are a major problem in the treatment of infectious diseases, such as pneumonia, meningitis, or even coronavirus disease 2019 (COVID-19). Cationic nanopolymers are a new type of antimicrobial agent with high efficiency. We synthesized and characterized cationic polymer based on 1,4-diazabicyclo [2.2.2] octane (DABCO) and Bis (bromoacetyl)cystamine (BBAC), named poly (DABCO-BBAC) nanoparticles(NPs), and produced 150 nm diameter NPs. The antibacterial activity of poly (DABCO-BBAC) against eight multi drug resistant (MDR) Pseudomonas aeruginosa isolates from human burns, its possible synergistic effect with gentamicin, and the mechanism of action were examined. Poly(DABCO-BBAC) could effectively inhibit and kill bacterial strains at a very low concentration calculated by minimum inhibitory concentration (MIC) assay. Nevertheless, its synergism index with gentamicin showed an indifferent effect. Moreover, transmission electron microscopy and lipid peroxidation assays showed that poly (DABCO-BBAC) distorted and damaged the bacterial cell wall. These results suggest that the poly (DABCO-BBAC) could be an effective antibacterial agent for MDR clinical pathogens.

Fetal Outcomes and Prognostic Factors After Radiofrequency Ablation for the Selective Reduction in Complicated Monochorionic Multiple Pregnancies.

RATIONALE AND OBJECTIVES: Monochorionic pregnancies are responsible for some severe complications, and selective reduction of a single fetus can improve pregnancy outcomes. This study evaluated the fetal outcomes and procedure-related prognostic factors after radiofrequency ablation (RFA) in complicated monochorionic multiple pregnancies. MATERIALS AND METHODS: This prospective cross-sectional study was conducted in an academic center from June 2020 to January 2022. The participants were 70 women with monochorionic multiple pregnancies who were candidates for selective fetal reduction by RFA. All participants' demographic data, RFA-related information, and pregnancy outcomes were evaluated and reported. RESULTS: The RFA procedure was successful in all participants. The most frequent RFA indications were twin-to-twin transfusion syndrome following selective intrauterine growth restriction. The mean gestational age at birth was 33.60 ± 5.62 weeks. Also, 11 (15.7%) of the cases had preterm delivery up to 30 days after RFA. The total pregnancy loss rate was 12 (17.14%), and the total fetal survival rate after RFA was 82.85%. The mean time of the RFA procedure was 130.8 ± 83.3 seconds. The procedure was conducted easily in 31 (44.2%) cases. Although the meantime of RFA procedure was longer in the not-easy group, the difference in surgery time was not significant (P = .296). There was no significant relationship (P = .623) between RFA indications and the gestational age of the remained fetus at delivery. The RFA needle was passed through the placenta in 18 (25.7%) cases. The mean gestational age at the delivery time was significantly lower in this group compared to their counterparts' gestational ages without needle placental passage (P = .030). Also, there was no significant correlation between gestational age at pregnancy termination and RFA cycles (P = .219). CONCLUSION: RFA is a relatively safe and minimally invasive procedure for the selective reduction of complicated monochorionic fetuses. Although mortality, premature membrane rupture, and preterm delivery are the potential risk factors for the remaining co-twin. According to this study, gestational age at the time of the procedure and passing the needle through the placenta can affect the outcome. Other procedure-related factors like easy- or hard-access procedures, and the number of RFA cycles are not significantly associated with gestational age at birth.

Importance of pre-operative COVID-19 screening test in elective surgeries.

Background and Objectives: Since the COVID-19 pandemic initiation, more than 28 million elective surgeries were postponed with a cancellation rate of 72.3%. However, studies suggested that the patient treatment should be conducted within 12 weeks of diagnosis because delay in treatment might have had adverse impacts on patients' health status, prognosis, and pathologic stage. Hence, the current study aimed to assess the importance of a pre-operative COVID-19 screening test for the patients were candidates for elective surgery. Materials and Methods: This cross-sectional study was conducted on 141 patients who were candidates for any type of elective surgeries or cesarean section at a tertiary university-based hospital, between June 2020, and September 2020. Results: The mean age of participants was 41.38 ± 11.66 years. Of them, 91.5% were women and 8.5% were men. The COVID-19 polymerase chain reaction (PCR) screening tests were positive in 12 (8.5%) patients. From whose PCR tests were positive, only five people (less than half) had symptoms of COVID-19 such as fever (three patients), a distinctive smell (two patients), and cough (one patient). Suspected exposure to COVID-19 was reported in four of them. Conclusion: In this study, we found that more than half of PCR positive COVID-19 patients were asymptomatic. Therefore, to have a safe hospital environment, and improve patient health outcomes, the COVID-19 screening test should be applied before any interventions.

Smart Strategies for Precise Delivery of CRISPR/Cas9 in Genome Editing.

The emergence of CRISPR/Cas technology has enabled scientists to precisely edit genomic DNA sequences. This approach can be used to modulate gene expression for the treatment of genetic disorders and incurable diseases such as cancer. This potent genome-editing tool is based on a single guide RNA (sgRNA) strand that recognizes the targeted DNA, plus a Cas nuclease protein for binding and processing the target. CRISPR/Cas has great potential for editing many genes in different types of cells and organisms both in vitro and in vivo. Despite these remarkable advances, the risk of off-target effects has hindered the translation of CRISPR/Cas technology into clinical applications. To overcome this hurdle, researchers have devised gene regulatory systems that can be controlled in a spatiotemporal manner, by designing special sgRNA, Cas, and CRISPR/Cas delivery vehicles that are responsive to different stimuli, such as temperature, light, magnetic fields, ultrasound (US), pH, redox, and enzymatic activity. These systems can even respond to dual or multiple stimuli simultaneously, thereby providing superior spatial and temporal control over CRISPR/Cas gene editing. Herein, we summarize the latest advances on smart sgRNA, Cas, and CRISPR/Cas nanocarriers, categorized according to their stimulus type (physical, chemical, or biological).

An Investigation of the Pathology Report of Bladder Cancer Patients with Radical Cystectomy in Southern Iran, 2013-2018: A Cross-Sectional Study.

Background: The oncological outcomes of bladder cancer are directly associated with disease pathology and surgical technique. Therefore, we investigated the pathologic factors of radical cystectomy (RC) specimens. Methods: In this retrospective study, 365 patients who underwent RC between March 2013 to March 2018 in hospitals affiliated to Shiraz University were enrolled. The patients' clinicopathological parameters, such as tumor type, tumor grade, carcinoma in situ, lymph node (LN) involvement, lymphovascular invasion (LVI), perineural invasion (PNI), and age, were recorded from their pathology reports. For comparison of variables, an independent t test was used. P < 0.05 was regarded as significant. The statistical software SPSS version 22 was used to examine the data. Results: The participants' mean age was 64.52 ± 11.54 years, and 320 (87.7%) patients were men and 45 (12.3%) were women. The mean dissected LN was 9.69 ± 8.70 nodes and 1.06 ±3.49 of the dissected LNs were involved by tumor. PNI and perivesical invasion were presented in 148 (40.5%) and 96 (26.3%) patients, respectively. Ureteral, urethral, and prostate involvements were seen in 23 (6.3%), 50 (13.7%), and 66 (18.1%) patients. Most patients had pathologic tumor stage 2 (36.4%). Factors such as LVI, PNI, perivesical invasion, and prostate involvement, were strongly correlated with positive LN (P ≤ 0.05). Conclusion: The examination of the RC specimen is critical for patient care, outcome, and justification of adjuvant therapy. Factors such as LVI, perineural invasion, perivesical invasion, and prostate involvement were strongly correlated with positive LN.

Dual Redox/pH-Sensitive Micelles Self-Assembled From Star-Like Amphiphilic Copolymers Based On Sucrose For Controlled Doxorubicin Delivery.

Novel dual redox/pH-sensitive star-like amphiphilic sucrose-oligo(butyl fumarate) (thioglycolic acid conjugate)-SS-poly(ethylene glycol) (Suc-OBF(TGA)-SS-PEG) copolymers and their self-assembled micelles were prepared and utilized for intracellular doxorubicin delivery. Importance of changing the hydrophobic chain length on micelles properties was investigated. Results showed that the micelles with longer hydrophobic chain exhibited smaller size and were more stable in aqueous solution. The redox and pH sensitivity of the micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic light scattering and the change of micellar morphology observed by scanning electron microscope. The micelles display a decent doxorubicin loading capacity. In vitro release studies showed that only 14.3% doxorubicin was released from doxorubicin-loaded micelles under physiological conditions in 30 h. The release of doxorubicin was accelerated at pH 5.5 or in the presence of 10 mM glutathione at pH 7.4 (46.9% and 76.9% of doxorubicin was released, respectively, in 30 h). The doxorubicin release was further expedited under pH 5.5 and 10 mM GSH conditions (91.4%). Suc-OBF(TGA)-SS-PEG micelles displayed no cytotoxicity toward HDF cells. MTT assays indicated that doxorubicin-loaded micelles had good cytotoxicity against MCF-7 cells. This work suggested that star-like amphiphilic Suc-OBF(TGA)-SS-PEG copolymer micelles may provide a promising platform for delivering doxorubicin and other hydrophobic anticancer drugs.

Comparison between novel star-like redox-sensitive amphiphilic block copolymer and its linear counterpart copolymer as nanocarriers for doxorubicin.

Linear and star-like redox-sensitive amphiphilic block copolymers have been studied as anticancer drug delivery systems. However, few reports directly compared the properties of those two structures especially when they are used as nanocarriers for antitumor drugs. To address this, a novel star-like copolymer and its linear counterpart were synthesized with a hydrophobic/redox-responsive/hydrophilic structure. The overall molecular weight of the star-shaped copolymer was nearly equal to that of the linear counterpart. The star-like micelles exhibit size of 90 nm, which was smaller than that of linear copolymers (151.6 nm) and critical micelle concentration of 1 mg/L, which was lower than that of the linear micelles (8.9 mg/L). The disassembly behaviors and the redox-sensitivity of the nanoparticles to reductive stimuli of glutathione was evaluated from the changes of the micellar size and morphology. Furthermore, doxorubicin was physically loaded into the hydrophobic part of the copolymers. The drug-loading capacities in the star-like and linear micelles were 15.94 and 7.53 wt%, respectively. Drug release studies carried out at two different glutathione concentrations. A cytotoxicity study of the micelles was performed by MTT assay. The prepared star copolymer showed no significant toxicity against HDF cells while enhanced cytotoxicity of the DOX-loaded micelles against MCF-7 cells was observed. Therefore, developing sucrose-PCL-SS-PEG copolymer reported in this paper as an effective reduction-responsive carrier with excellent properties and cell biocompatibility is promising for the efficient intracellular delivery of hydrophobic chemotherapeutic drugs. This work also indicates that modification of the nanocarrier structure is a potential strategy for optimizing drug delivery.