Ketoprofen suppresses triple negative breast cancer cell growth by inducing apoptosis and inhibiting autophagy.

BACKGROUND: Triple-negative breast cancer (TNBC) is an invasive phenotype with undesirable clinical features, poor prognosis, and therapy resistance. Ketoprofen is a Non-steroidal anti-inflammatory drug (NSAID) with anti-tumor properties. AIM: To investigate the effects of Ketoprofen on apoptosis and autophagy in TNBC cell line MDA-MB-231. METHODS: The cytotoxic activity of Ketoprofen was assayed by the MTS method. Flowcytometry was utilized to measure the number of apoptotic MDA-MB-231 cells. The expression levels of apoptosis and autophagy markers, JAK2 and STAT3 were determined using quantitative real time-PCR (qRT-PCR) and western blotting methods. RESULTS: Ketoprofen significantly decreased the proliferation of MDA-MB-231 cells compared to control cells. It also considerably induced apoptosis and apoptotic markers in these cells in comparison to controls. Treating the MADA-MB-231 cell line with Ketoprofen had an inhibitory effect on autophagy markers in this cell line. The use of FasL, as a death ligand, and ZB4, as an antibody that blocks the extrinsic pathway of apoptosis, revealed the involvement of the extrinsic pathway in the apoptosis-stimulating effect of Ketoprofen in the MADA-MB-231 cell line. Ketoprofen also hindered the phosphorylation and activation of JAK2 and STAT molecules leading to the inhibition of the JAK/STAT pathway in this TNBC cell line. CONCLUSION: The outcomes of this study uncovered the anti-TNBC activity of Ketoprofen by inducing apoptosis and inhibiting viability and autophagy in MADA-MB-231 cells. Our data also suggested that Ketoprofen impedes apoptosis in TNBC cells by two different mechanisms including the induction of the extrinsic apoptotic pathway and inhibition of the JAK/STAT signaling.

Roles of CCR10/CCL27-CCL28 axis in tumour development: mechanisms, diagnostic and therapeutic approaches, and perspectives.

Cancer is now one of the major causes of death across the globe. The imbalance of cytokine and chemokine secretion has been reported to be involved in cancer development. Meanwhile, CC chemokines have received considerable interest in cancer research. CCR10, as the latest identified CC chemokine receptor (CCR), has been implicated in the recruitment and infiltration of immune cells, especially lymphocytes, into epithelia such as skin via ligation to two ligands, CCL27 and CCL28. Other than homoeostatic function, several mechanisms have been shown to dysregulate CCR10/CCL27-CCL28 expression in the tumour microenvironment. As such, these receptors and ligands mediate T-cell trafficking in the tumour microenvironment. Depending on the types of lymphocytes recruited, CCR10/CCL27-CCL28 interaction has been shown to play conflicting roles in cancer development. If they were T helper and cytotoxic T cells and natural killer cells, the role of this axis would be tumour-suppressive. In contrast, if CCR10/CCL27-CCL28 recruited regulatory T cells, cancer-associated fibroblasts or myeloid-derived suppressor cells, it would lead to tumour progression. In addition to the trafficking of lymphocytes and immune cells, CCR10 also leads to the migration of tumour cells or endothelial cells (called angiogenesis and lymphangiogenesis) to promote tumour metastasis. Furthermore, CCR10 signalling triggers tumour-promoting signalling such as PI3K/AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase, resulting in tumour cell growth. Since CCR10/CCL27-CCL28 is dysregulated in the tumour tissues, it is suggested that analysis and measurement of them might predict tumour development. Finally, it is hoped using therapeutic approaches based on this axis might increase our knowledge to overcome tumour progression.

Clinical management and recommendations for children with more than four episodes of recurrent intussusception following successful reduction of each: an institutional review.

AIM: To describe patterns and risk factors of multiple recurrences to optimise management for pediatric patients with more than four episodes of intussusception. MATERIALS AND METHODS: Following IRB approval, all sonographic evaluations for intussusception in patients <18 years over a 6-year period were reviewed. Data extracted included age at onset of first intussusception, gender, presenting symptoms, symptoms upon recurrence, presence of pathological lead points, and surgical findings. RESULTS: During a 6-year period, five cases had four or more instances of recurrence after enema reduction attempts. All patients were male with an average age of 16 months. Two of the five cases resolved after the fourth enema reduction and no lead points were identified. Two other cases involved surgical reduction with intraoperative findings of Meckel's diverticulum and juvenile polyp. The final case had five recurrence episodes and six separate enema reductions. Ultimately, lymphoid hyperplasia was discovered on colonoscopy and the patient never recurred after being treated with steroids. CONCLUSION: Given the favorable reduction rate in re-recurrent cases and complete lack of perforation observed, up to four attempts at enema reduction is recommended before considering an alternative strategy. If recurrence continues past the fourth reduction attempt, computed tomography (CT) is recommended to identify a lead point. If CT remains inconclusive, then consider exploratory laparotomy.

Exploring the Impact of Cigarette Smoke Extracts on Vitamin B12: Insights into the Transformation of Methylcobalamin and Hydroxycobalamin to Cyanocobalamin through In Vitro Evaluation.

Vitamin B12 (cobalamin) is a water-soluble molecule required for the proper functioning of metabolism, blood and DNA synthesis, and neurological development. Vitamin B12 exists in several forms: methylcobalamin (MeCbl), adenosylcobalamin (AdoCbl), hydroxycobalamin (OHCbl), and cyanocobalamin (CNCbl). This study aimed to evaluate the effect of cigarette smoke on the chemical structure of methylcobalamin and hydroxycobalamin forms of vitamin B12. MeCbl and OHCbl were markedly affected by exposure to cigarette smoke. The resemblance of the Rt between MeCbl and OHCbl and CNCbl indicates that exposure to cigarette smoke extracts chemically alters MeCbl and OHCbl to CNCbl, warranting in vivo research investigations.

Identification and characterization of a novel lytic peptidoglycan transglycosylase (MltC) in Shigella dysenteriae.

Shigellosis remains a worldwide health problem due to the lack of vaccines and the emergence of antibiotic-resistant strains. Shigella (S.) dysenteriae has rigid peptidoglycan (PG), and its tight regulation of biosynthesis and remodeling is essential for bacterial integrity. Lytic transglycosylases are highly conserved PG autolysins in bacteria that play essential roles in bacterial growth. However, their precise functions are obscure. We aimed to identify, clone, and express MltC, a unique autolysin in Escherichia (E.) coli C41 strain. The purification of recombinant MltC protein was performed using affinity chromatography and size-exclusion chromatography methods. The PG enzymatic activity of MltC was investigated using Zymogram and Fluorescein isothiocyanate (FITC)-labeled PG assays. Also, we aimed to detect its localization in bacterial fractions (cytoplasm and membrane) by western blot using specific polyclonal anti-MltC antibodies and its probable partners using immunoprecipitation and mass spectrometry applications. Purified MltC showed autolysin activity. Native MltC showed various locations in S. dysenteriae cells during different growth phases. In the Lag and early stationary phases, MltC was not found in cytoplasm and membrane fractions. However, it was detected in cytoplasm and membrane fractions during the exponential phase. In the late stationary phase, MltC was expressed in the membrane fraction only. Different candidate protein partners of MltC were identified that could be essential for bacterial growth and pathogenicity. This is the first study to suggest that MltC is indeed autolysin and could be a new drug target for the treatment of shigellosis by understanding its biological functions.

Behavior and anxiety levels in pediatric patient: The behavioral changes and anxiety of pediatric patient in dental clinic.

AIM: The aim of this study is to evaluate the behavioral patterns and anxiety levels of pediatric patients in dental clinics, discern their behavioral expectations, and investigate the associations between these factors and the patient's age and gender. METHODS: In this cross-sectional study, 150 pediatric patients visiting Sharjah Thumbay Dental Hospital for treatment were recruited over a study period of 23 weeks (February 12, 2022 to July 23, 2022). The patient's age ranged from 2 to 14 years. Guardians were informed about the study and their written consent was taken. EXCLUSION CRITERIA: Children over 14 years old, children whose guardians refused to participate in the study, and medically compromised children. Frankl's behavior rating scale, Categorical rating scale, and Venham anxiety and behavioral rating scales were used to evaluate the pediatric patient's behavior and anxiety at the end of the dental visit, the evaluation was done by the same trained dental student for all the patients. RESULTS: When the Mann-Whitney U test was used for gender, no significant differences were observed in behavior and anxiety between male and female patients across all scales employed in this study. Conversely, when examining various age groups for behavior and anxiety using the Kruskal-Wallis test, significant findings emerged across nearly all scales. In the categorical rating scale, the age group of 11-14 years exhibited the most notable results in subscales of crying (p = .034), cooperativeness (p = .002), and apprehensiveness (p = .003). CONCLUSION: The pediatric patients who took part in this study exhibited heightened anxiety when attending dental clinics. This study underscores the importance of understanding child behavior and utilizing effective communication with children and their guardians. Dental professionals should consider implementing strategies to manage child behavior during visits. Further research is required to develop sufficient strategies tailored to different pediatric populations, aiming to enhance dental care outcomes for pediatric patients.

A microfluidic biosensor for the diagnosis of chronic wasting disease.

Cervids are affected by a neurologic disease that is always fatal to individuals and has population effects. This disease is called chronic wasting disease (CWD) and is caused by a misfolded prion protein. The disease is transmitted via contact with contaminated body fluids and tissue or exposure to the environment, such as drinking water or food. Current CWD diagnosis depends on ELISA screening of cervid lymph nodes and subsequent immunohistochemistry (IHC) confirmation of ELISA-positive results. The disease has proven to be difficult to control in part because of sensitivity and specificity issues with the current test regimen. We have investigated an accurate, rapid, and low-cost microfluidic microelectromechanical system (MEMS) biosensing device for the detection of CWD pathologic prions in retropharyngeal lymph nodes (RLNs), which is the current standard type of CWD diagnostic sample. The device consists of three novel regions for concentrating, trapping, and detecting the prion. The detection region includes an array of electrodes coated with a monoclonal antibody against pathologic prions. The experimental conditions were optimized using an engineered prion control antigen. Testing could be completed in less than 1 hour with high sensitivity and selectivity. The biosensor detected the engineered prion antigen at a 1:24 dilution, while ELISA detected the same antigen at a 1:8 dilution. The relative limit of detection (rLOD) of the biosensor was a 1:1000 dilution of a known strong positive RLN sample, whereas ELISA showed a rLOD of 1:100 dilution. Thus, the biosensor was 10 times more sensitive than ELISA, which is the currently approved CWD diagnostic test. The biosensor's specificity and selectivity were confirmed using known negative RPLN samples, a negative control antibody (monoclonal antibody against bovine coronavirus BCV), and two negative control antigens (bluetongue virus and Epizootic hemorrhagic disease virus). The biosensor's ability to detect pathogenic prions was verified by testing proteinase-digested positive RLN samples.

Evaluation of Cholesterol Thickness of Blood Vessels Using Photoacoustic Technology.

One of the primary indicators of plaque vulnerability is the lipid composition of atherosclerotic plaques. Therefore, the medical industry requires a method to evaluate necrotic nuclei in atherosclerosis imaging with sensitivity. In this regard, photoacoustic imaging is a plaque detection method that provides chemical information on lipids and cholesterol thickness in the arterial walls of the patient. This aspect aims to increase the low-frequency axial resolution by developing a new photoacoustic-based system. A photoacoustic system has been developed to detect the cholesterol thickness of the blood vessels to observe the progression of plaque in the heart's blood vessels. The application of the coherent photoacoustic discontinuous correlation tomography technique, which is based on a novel signal processing, significantly increased the cholesterol oleate's sensitivity to plaque necrosis. By enhancing the quality of thickness detection, the system for measuring the thickness of cholesterol in blood vessels has been reduced to approximately 23 microns. The results show that the phase spectrum peaked at 100 Hz at 58.66 degrees, and at 400 Hz, the phase spectrum was 46.37 degrees. The minimum amplitude is 1.95 at 100 Hz and 17.67 at 400 Hz. In conclusion, it can be stated that photoacoustic imaging as a method based on new technologies is of great importance in medical research, which is based on the use of nonionizing radiation to perform diagnostic processes and measure different types of body tissues.

A microfluidic biosensor architecture for the rapid detection of COVID-19.

The lack of enough diagnostic capacity to detect severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has been one of the major challenges in the control the 2019 COVID pandemic; this led to significant delay in prompt treatment of COVID-19 patients or accurately estimate disease situation. Current methods for the diagnosis of SARS-COV-2 infection on clinical specimens (e.g. nasal swabs) include polymerase chain reaction (PCR) based methods, such as real-time reverse transcription (rRT) PCR, real-time reverse transcription loop-mediated isothermal amplification (rRT-LAMP), and immunoassay based methods, such as rapid antigen test (RAT). These conventional PCR methods excel in sensitivity and specificity but require a laboratory setting and typically take up to 6 h to obtain the results whereas RAT has a low sensitivity (typically at least 3000 TCID50/ml) although with the results with 15 min. We have developed a robust micro-electro-mechanical system (MEMS) based impedance biosensor fit for rapid and accurate detection of SARS-COV-2 of clinical samples in the field with minimal training. The biosensor consisted of three regions that enabled concentrating, trapping, and sensing the virus present in low quantities with high selectivity and sensitivity in 40 min using an electrode coated with a specific SARS-COV-2 antibody cross-linker mixture. Changes in the impedance value due to the binding of the SARS-COV-2 antigen to the antibody will indicate positive or negative result. The testing results showed that the biosensor's limit of detection (LoD) for detection of inactivated SARS-COV-2 antigen in phosphate buffer saline (PBS) was as low as 50 TCID50/ml. The biosensor specificity was confirmed using the influenza virus while the selectivity was confirmed using influenza polyclonal sera. Overall, the results showed that the biosensor is able to detect SARS-COV-2 in clinical samples (swabs) in 40 min with a sensitivity of 26 TCID50/ml.

Radiotherapy-associated sensorineural hearing loss in pediatric oncology patients.

During the radiotherapeutic treatment of pediatric oncology patients, they would be at a latent risk of developing ionizing radiation-induced ototoxicity when the cochlea or auditory nerve is located within the radiation field. Sensorineural hearing loss (SNHL) is an irreversible late complication of radiotherapy, and its incidence depends on various factors such as the patient's hearing sensitivity, total radiation dose to the cochlea, radiotherapy fractionation regimen, age and chemoradiation. Importantly, this complication exhibits serious challenges to adult survivors of childhood cancer, as it has been linked to impairments in academic achievement, psychosocial development, independent living skills, and employment in the survivor population. Therefore, early detection and proper management can alleviate academic, speech, language, social, and psychological morbidity arising from hearing deficits. In the present review, we have addressed issues such as underlying mechanisms of radiation-induced SNHL, audiometric findings of pediatric cancer patients treated with radiotherapy, and management and protection measures against radiation-induced ototoxicity.

Find new channel for overcoming chemoresistance in cancers: Role of stem cells-derived exosomal microRNAs.

Chemoresistance has remained a significant concern in tumor recurrence and elevated cancer-related mortalities. A deep insight into mechanisms by which cancerous cells resist administered drugs can pave the way to overcome chemotherapy-induced cell death and develop novel procedures to rescue patients. Regarding accumulated data, stem cell-derived exosomal microRNAs (miRNAs) can be deemed a novel and promising method to overcome chemoresistance. It seems exosomal miRNAs play a dual role in the cancer microenvironment. On the one hand, as a messenger, they are transferred between donor and recipient cells contributing to cancer chemoresistance. On the other hand, stem cell-derived exosomal miRNA significantly restrains tumorigenesis and inhibits or alleviates drug resistance in the tumor niche. Hence, our purpose in this review evaluating the roles of stem cells-derived exosomal microRNAs in overcoming chemoresistance in tumors.

A microfluidic biosensor for rapid simultaneous detection of waterborne pathogens.

A microfluidic based biosensor was investigated for rapid and simultaneous detection of Salmonella, Legionella, and Escherichia coli O157:H7 in tap water and wastewater. The biosensor consisted of two sets of focusing electrodes connected in parallel and three sets of interdigitated electrodes (IDE) arrays. The electrodes enabled the biosensor to concentrate and detect bacteria at both low and high concentrations. The focusing region was designed with vertical metal sidewall pairs and multiple tilted thin-film finger pairs to generate positive dielectrophoresis (p-DEP) to force the bacteria moving toward the microchannel centerline. As a result, the bacterial pathogens were highly concentrated when they reached the detection electrode arrays. The detection IDE arrays were coated with three different antibodies against the target bacterial pathogens and a cross-linker to enhance the binding of antibodies to the detection electrode. As the binding of bacterial pathogen to its specific antibodies took place, the impedance value changed. The results demonstrated that the biosensors were capable of detecting Salmonella, Legionella, and E. coli 0157:H7 simultaneously with a detection limit of 3 bacterial cells/ml in 30 - 40 min.

Detection of abemaciclib, an anti-breast cancer agent, using a new electrochemical DNA biosensor.

Detection of DNA molecules and possible chemotherapy-induced changes in its structure has been the goal of researchers using rapid, sensitive and inexpensive approaches. Therefore, the aim of this study was to fabricate a new electrochemical DNA biosensor using pencil graphite electrodes modified with polypyrrole/Ce doped hexagonal nickel oxide nanodisks or PP/Ce-doped H-NiO-ND composites for determination of Abemaciclib (AMC) and ds-DNA molecules. The DNA biosensor was prepared by immobilizing ds-DNA on the surface of PP/Ce-doped H-NiO-ND/PGE. Differential pulse voltammetry (DPV) was used to electrochemically detect AMC. The results elucidate the extremely high sensitivity of the ds-DNA/PP/Ce-doped H-NiO-ND/PGE biosensor to AMC, with a narrow detection limit of 2.7 nM and a lengthy linear range of 0.01-600.0 µM. The admirable performance of as-fabricated biosensor could be related to the active reaction sites and the unique electrochemical response related to the nanocomposites by enhancing ds-DNA stabilization and accelerating electron transfer on the surface of electrode.

Factors Affecting Compliance to Anti-Vascular Endothelial Growth Factor Treatment of Diabetic Macular Edema in a Cohort of Jordanian Patients.

PURPOSE: To determine compliance rates and characteristics and to investigate factors affecting patients' adherence to treatment with anti-vascular endothelial growth factors (anti-VEGFs) for diabetic macular edema (DME) in a cohort of Jordanian patients. METHODS: A retrospective case series wherein the files of DME patients treated with anti-VEGFs were reviewed and analyzed for factors affecting treatment compliance was undertaken. Demographic, clinical and ocular characteristics were recorded. All patients were also interviewed by phone using a structured questionnaire. Univariate and multivariate analyses were performed to determine factors associated with compliance. RESULTS: A total of 117 patients (65 males 52 females) were included in this study with a mean age of 62.93 years (±9.75). Approximately, 85% of patients were compliant to their treatment and follow-up plan during the first year of management. Subjective perception of visual improvement after receiving three loading doses was the only independent variable with a unique statistically significant contribution to compliance. All other studied factors in this group of patients were not significantly associated with patient compliance. CONCLUSION: VEGF suppression via the intravitreal route to treat DME is a long-term process that requires caregiver dedication but also proper patient compliance. Addressing real-life barriers in those patients may help guide future strategies to improve the treatment experience, lower the financial burden and contribute to better outcomes. Patients' perceptions of possible treatment outcomes at the short term may influence their long-term commitment to therapy.

Epileptic Patients are at Risk of Cardiac Arrhythmias: A Novel Approach using QT-nomogram, Tachogram, and Cardiac Restitution Plots.

BACKGROUND: Sudden death is reported in patients who had a history of epilepsy and some authors believed that is due to cardiac arrhythmias. OBJECTIVES: This study aimed to predict that the epileptic patients are at risk of serious cardiac arrhythmias by QT-nomogram, tachogram (Lorenz), and cardiac restitution plots. METHODS: A total number of 71 healthy subjects (Group I) and 64 newly diagnosed epileptic patients (Group II) were recruited from Al-Yarmouk and Baghdad Teaching hospitals in Baghdad from March 2015 to July 2015 and included in this study. The diagnosis of epilepsy achieved clinically, electroencephalograph record and radio-images including computerized tomography and magnetic image resonance. At the time of entry into the study, an electrocardiography (ECG) was done, and the determinants of each ECG record were calculated. The QT-nomogram, tachogram, and cardiac restitution plots were used to identify the patients at risk of cardiac arrhythmias. RESULTS: Significant prolonged corrected QT corrected (QTc) and JT corrected intervals were observed in female compared with male at age ≥50 years while the TQ interval was significantly prolonged in males of Group II. Eight patients of Group II had a significant pathological prolonged QTc interval compared with undetectable finding in Group I. QT nomogram did not disclose significant findings while the plots of Lorenz and restitution steepness disclose that the patients of Group II were vulnerable to cardiac arrhythmias. Abnormal ECG findings were observed in the age extremities (≤18 years and ≥50 years) in Group II compared with Group I. CONCLUSION: Utilization of QT-nomogram, restitution steepness, and tachogram plots is useful tools for detection subclinical vulnerable epileptic patient with cardiac arrhythmias.

Selectively bred male rat lines differ in naïve and experienced sexual behavior.

Ejaculatory behavior is facilitated by activating 5-hydroxytryptamine(1A) (5-HT(1A)) receptors. The present study examined male sexual behavior in rat lines that were selectively bred for their different hypothermic responses to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Sexual behavior was examined in naïve and experienced HDS (high 8-OH-DPAT sensitive), LDS (low 8-OH-DPAT sensitive), and RDS (randomly bred) rats lines. In addition, the effects of 8-OH-DPAT (0.05 mg/kg) and N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl)-cyclohexane-carboxamide (WAY 100,635; 1 mg/kg) were examined. Naïve HDS animals had diminished ejaculatory behavior (as indicated by a decreased number of intromissions, mounts and ejaculations, increased ejaculation and intromission latency, and longer inter-copulatory interval), compared to the LDS and RDS groups. In addition, the post-ejaculatory interval (PEI) was longer in the HDS group. With experience, the HDS group improved its ejaculatory behavior. Experienced HDS animals had a lower number of intromissions and a longer PEI compared to the LDS group. 8-OH-DPAT facilitated ejaculatory behavior in both HDS and LDS groups. This effect was more pronounced in the LDS group. WAY 100,635 did not alter sexual behavior in either group. In summary, alteration in forebrain 5-HT(1A) receptors in HDS animals may be involved in the ability of naïve rats to achieve ejaculation. 5-HT(1A) receptors are involved in the regulation of resumption of sexual behavior after ejaculation.

Prostate carcinoma metastatic to the cervical lymph nodes: report of two cases and review of the literature.

The cervical lymph nodes are a common site of metastasis for cancers originating in the upper aerodigestive tract. Rarely, cancers originating from sites other than the head and neck can metastasize to the cervical lymph node chain. We report on 2 recent patients with metastatic prostate cancer to the cervical lymph nodes.