Drug Treatment Research Articles

Upregulation of key factors of viral entry of corona- and influenza viruses upon TLR3-signaling in cells from the respiratory tract and clinical treatment options by 1,8-Cineol.

At the end of the 2019 coronavirus pandemic (COVID-19), highly contagious variants of coronaviruses had emerged. Together with influenza viruses, different variants of the coronavirus currently cause most colds and require appropriate drug treatment. We have investigated the expression of important factors for the replication of these viruses, namely transmembrane protease serine subtype 2 (TMPRSS2), neuropilin1 (NRP1), and angiotensin converting enzyme 2 (ACE2) or tumor necrosis factor-α (TNF-α) after toll like receptor-3 (TLR-3) stimulation using RT-qPCR and flow cytometry (FC) analysis. As model served primary fibroblasts derived from the lung and nasal cavity, as well as epidermal stem cells and fully matured respiratory epithelium. The stimulated cell cultures were treated with pharmaceuticals (Dexamethasone and Enzalutamide) and the outcome was compared with the phytomedicine 1,8-Cineol. The stimulation of TLR3 is sufficient to induce the expression of exactly those targets that were highly expressed in the corresponding culture type, specifically ACE2 and TMPRSS2 in respiratory epithelial stem cells and NRP1 in fibroblast cells. It seems this self-perpetuating cycle of infection-driven upregulation of key viral replication factors by the innate immune system represents an evolutionary advantage for viruses using these transcripts as viral replication factors. Likewise, to the standard pharmaceuticals with proven clinical efficiency, 1,8-Cineol was able to disrupt this self-perpetuating cycle. Considering the minor side effects and negligible pharmacological interactions with other drugs, it is conceivable that an adjuvant or combinatorial therapy with 1,8-Cineol for respiratory diseases caused by corona- or influenza viruses would be beneficial.

Deciphering the Temporal-Spatial Interactive Heterogeneity of Long Non-Coding RNAs and RNA-Binding Proteins in Living Cells at Single-Cell Resolution.

The investigation of long noncoding RNAs (lncRNAs) and RNA binding proteins (RBPs) interactions in living cell holds great significance for elucidating their critical roles in a variety of biological activities, but limited techniques are available to profile the temporal-spatial dynamic heterogeneity. Here, we introduced a molecular beacon-functionalized nanoneedle array designed for spatially resolved profiling of lncRNA-RBP interactions (Nano-SpatiaLR). A nanoneedle array modified with a molecular beacon is employed to selectively isolate specific intracellular lncRNAs and their associated RBPs without affecting cell viability. The RBPs are then in situ analyzed with a fluorescent labeled antibody and colocalized with lncRNA signals to get a quantitative measurement of their dynamic interactions. Additionally, leveraging the spatial distribution and nanoscale modality of the nanoneedle array, this technique provides the spatial heterogeneity information on cellular lncRNA-RBPs interaction at single cell resolution. In this study, we tracked the temporal-spatial interactive heterogeneity dynamics of lncRNA-RBPs interaction within living cells across different biological progresses. Our findings demonstrated that the interactions between lncRNA HOTAIR and RBPs EZH2 and LSD1 undergo significant changes in response to drug treatments, particularly in tumor cells. Moreover, these interactions become more intensified as tumor cells aggregate during the proliferation process.

Intrinsically bioactive multifunctional Poly(citrate-curcumin) for rapid lung injury and MRSA infection therapy

Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.

Computer Aided Diagnostics and Local Drug Treatment (Case Reports)

Computer Aided Diagnostics and Local Drug Treatment (Case Reports)

Placebo treatment affects brain systems related to affective and cognitive processes, but not nociceptive pain

Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study (N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.

Differently increased volumes of multiple brain areas in Npc1 mutant mice following various drug treatments

BackgroundNiemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of Npc1−/− displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholesterol storage. Npc1−/− mice receiving a combined therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) showed prevention of Purkinje cell loss, improved motor function and reduced intracellular lipid storage. Although therapy of Npc1−/− mice with COMBI, MIGLU or HPßCD resulted in the prevention of body weight loss, reduced total brain weight was not positively influenced.MethodsIn order to evaluate alterations of different brain areas caused by pharmacotherapy, fresh volumes (volumes calculated from the volumes determined from paraffin embedded brain slices) of various brain structures in sham- and drug-treated wild type and mutant mice were measured using stereological methods.ResultsIn the wild type mice, the volumes of investigated brain areas were not significantly altered by either therapy. Compared with the respective wild types, fresh volumes of specific brain areas, which were significantly reduced in sham-treated Npc1−/− mice, partly increased after the pharmacotherapies in all treatment strategies; most pronounced differences were found in the CA1 area of the hippocampus and in olfactory structures.DiscussionVolumes of brain areas of Npc1−/− mice were not specifically changed in terms of functionality after administering COMBI, MIGLU, or HPßCD. Measurements of fresh volumes of brain areas in Npc1−/− mice could monitor region-specific changes and response to drug treatment that correlated, in part, with behavioral improvements in this mouse model.

Rifabutin loaded inhalable β-glucan microparticle based drug delivery system for pulmonary TB

Inhalable microparticle-based anti TB drug delivery systems are being investigated extensively for Tuberculosis [TB] treatment as they offer efficient and deep lung deposition with several advantages over conventional routes. It can reduce the drug dose, treatment duration and toxic effects and optimize the drug bioavailability. Yeast derived β-glucan is a β-[1–3/1–6] linked biocompatible polymer and used as carrier for various biomolecules. Due to presence of glucan chains, particulate glucans act as PAMP and thereby gets internalized via receptor mediated phagocytosis by the macrophages. In this study, β-glucan microparticles were prepared by adding l-leucine as excipient, and exhibited 70% drug [Rifabutin] loading efficiency. Further, the sizing and SEM data of particles revealed a size of 2–4 µm with spherical dimensions. The FTIR and HPLC data confirmed the β-glucan composition and drug encapsulations efficiency of the particles. The mass median aerodynamic diameter [MMAD] and geometric standard deviation [GSD] data indicated that these particles are inhalable in nature and have better thermal stability as per DSC thermogram. These particles were found to be non-toxic upto a concentration of 80 µg/ml and were found to be readily phagocytosed by human macrophage cells in-vitro as well as in-vivo by lung alveolar macrophage. This study provides a framework for future design of inhalable β-glucan particle based host-directed drug delivery system against pulmonary TB.

Role of Brown Adipose Tissue in Metabolic Health and Efficacy of Drug Treatment for Obesity

(1) Background: Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, and its activation has become a new object as both a determinant of metabolic health and a target for therapy. This study aimed to identify the relationships between the presence of BAT, parameters that characterize metabolic health (glucose, lipids, blood pressure (BP)), and the dynamics of body mass index (BMI) during weight-reducing therapy. (2) Methods: The study included 72 patients with obesity. We investigated metabolic parameters, anthropometric parameters, and BP. Dual-energy X-ray absorptiometry (DXA) and positron emission tomography and computed tomography (PET/CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) were performed. (3) Results: Before weight-reducing therapy, BAT was revealed only in 19% patients with obesity. The presence of BAT was associated with a lower risk of metabolic deviations that characterize metabolic syndrome: shorter waist circumference (WC) (p = 0.02) and lower levels of glucose (p = 0.03) and triglycerides (p = 0.03). Thereafter, patients were divided into four groups according to the type of therapy (only lifestyle modification or with Liraglutide or Reduxin or Reduxin Forte). We did not find a relationship between the presence of BAT and response to therapy: percent weight reduction was 10.4% in patients with BAT and 8.5% in patients without BAT (p = 0.78) during six months of therapy. But we noted a significant positive correlation between the volume of BAT and the effectiveness of weight loss at 3 months (r = 0.52, p = 0.016). The dynamic analysis of BAT after 6 months of therapy showed a significant increase in the volume of cold-induced metabolically active BAT, as determined by PET/CT with 18F-FDG in the Liraglutide group (p = 0.04) and an increase in the activity of BAT standardized uptake value (SUV mean and SUV max) in the Reduxin (p = 0.02; p = 0.01, respectively) and Liraglutide groups (p = 0.02 in both settings). (4) Conclusions: The presence of brown adipose tissue is associated with a lower risk of metabolic abnormalities. In general, our study demonstrated that well-established drugs in the treatment of obesity (Liraglutide and Reduxin) have one more mechanism for implementing their effects. These drugs have the ability to increase the activity of BAT. A significant positive relationship between the total volume of BAT and the percentage of weight loss may further determine the priority mechanism of the weight-reducing effect of these medicaments.

Features of diagnosis and treatment of a child with choledochal cyst IС type

Choledochal cysts are congenital cystic dilatations of the extrahepatic and/or intrahepatic bile ducts. Diagnosis and choice of treatment tactics for this pathology often cause difficulties. A case report of a choledochal cyst in a 2-year-old patient with symptoms of recurrent jaundice, cholangitis, and pancreatitis, which required laparoscopic cholecystostomy and cholangiography during preparation for radical surgery, was retrospectively analyzed. The child was re-admitted to the pediatric surgical department with complaints of hyperthermia up to 39°C, resumption of periodic abdominal pain, nausea, and increased icterus of the sclera and skin. Laboratory and ultrasound examination indicated biliary and pancreatic hypertension. Choledochal cyst, cholestasis syndrome, acute cholecystopancreatitis was diagnosed. Owing to the existing clinical symptoms and laboratory and ultrasound data, laparoscopic cholecystostomy was urgently performed. Against the background of conservative therapy, within 2 days after laparoscopic cholecystostomy, clinically, laboratory and according to control ultrasound examination, biliary and pancreatic hypertension were stopped. The child underwent cholangiography through a cholecystostomy without additional anesthesia, which revealed a fusiform dilatation of the common hepatic and bile ducts. After 2 weeks of drug treatment against the background of laparoscopic cholecystostomy, the child underwent excision of the common bile duct cyst, and cholecystectomy with hepatic enteroanastomosis on a Roux-en-Y loop. The postoperative period was smooth. No other complaints or complications were noted within 24 months. In the reported case, recurrent obstructive jaundice was caused by a choledochal cyst. Laparoscopic cholecystostomy enabled the quick and successful relief of biliary hypertension, preparation of the patient for radical surgical treatment, and safe informative cholangiography through cholecystostomy. Hepatic enteroanastomosis with a disconnected loop according to Roux-en-Y was an effective surgical treatment method for choledochal cyst.

CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there is no effective drug treatment. Atherosclerosis (AS) is caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, and NASH can also elevate the risk of AS, causing a higher morbidity and mortality rate for atherosclerotic heart disease. Therefore, timely detection and diagnosis of NASH and AS are particularly important. In this study, differential gene expression analysis and weighted gene co-expression network analysis were performed on the AS (GSE100927) and NASH (GSE89632) datasets to obtain common crosstalk genes, respectively. Then, candidate Hub genes were screened using four topological algorithms and externally validated in the GSE43292 and GSE63067 datasets to obtain Hub genes. Furthermore, immune infiltration analysis and gene set variation analysis were performed on the Hub genes to explore the underlying mechanisms. The DGIbd database was used to screen candidate drugs for AS and NASH. Finally, a NASH model was constructed using free fatty acid-induced human L02 cells, an AS model was constructed using lipopolysaccharide-induced HUVECs, and a co-morbidity model was constructed using L02 cells and HUVECs to verify Hub gene expression. The result showed that a total of 113 genes common to both AS and NASH were identified as crosstalk genes, and enrichment analysis indicated that these genes were mainly involved in the regulation of immune and metabolism-related pathways. 28 candidate Hub genes were screened according to four topological algorithms, and CXCL9, IL2RB, and SPP1 were identified as Hub genes after in vitro experiments and external dataset validation. The ROC curves and SVM modeling demonstrated the good diagnostic efficacy of these three Hub genes. In addition, the Hub genes are strongly associated with immune cell infiltration, especially macrophages and γ–δ T cell infiltration. Finally, five potential therapeutic drugs were identified. has-miR-185 and hsa-miR-335 were closely related to AS and NASH. This study demonstrates that CXCL9, IL2RB, and SPP1 may serve as potential biomarkers for the diagnosis of the co-morbidity patterns of AS and NASH and as potential targets for drug therapy.

Antihypertensive drug treatment and the risk for intra-hemodialysis hypotension.

Antihypertensive medications are often prescribed to manage hypertension in hemodialysis (HD) patients, and intradialytic hypotension (IDH) is a common complication in these patients. We investigated the risk of IDH in incident HD patients who initiated treatment with antihypertensive drugs in monotherapy. The study was conducted as an emulation of a randomized clinical trial in 4072 incident HD patients who started anti-hypertensive drug treatment between January 2016 to December 2019. The primary outcome was the occurrence of IDH during HD sessions. The Gener alised Estimating Equation (GEE) analysis was adjusted by inverse probability treatment weighting (IPTW). Calcium channel blocker (CCB) use was associated with an IDH incidence rate of 7.4 events per person-year (95% CI: 6.2-8.6). Compared to CCB use, use of beta and alpha-beta blockers was strongly associated with a higher likelihood of IDH (OR [95% CI] 2.27 [1.50-3.43]). Use of angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (OR [95% CI] 1.71 [1.14-2.57]) and diuretics (OR [95% CI] 1.52 [1.07-2.16]) were also associated with higher likelihood of IDH compared to CCB use. The study suggests that using beta and alpha-beta blockers, ACE inhibitors or angiotensin II receptor blockers, and diuretics may increase the risk of IDH in HD patients compared to CCB use.

Examination of drug removal profiles in patients undergoing therapeutic plasma exchange: A retrospective study.

Therapeutic plasma exchange (TPE) eliminates disease-contributing substances but may also affect drug concentrations. This study aimed to assess the prevalence of prescription drugs removable via TPE by reviewing patient medication histories. A retrospective, single-center study was conducted from January 1, 2021 to December 31, 2022. The study included 244 patients undergoing 1087 TPE sessions. Drugs prescribed to patients on TPE days were categorized as "yes" (probably removable), "maybe" (possibly removable), and "no" (unlikely removable) regarding their removability via TPE. Among 3966 prescriptions, 556 (14.0%) were analyzed, with 21.8%, 36.5%, and 41.7% falling into the "yes," "maybe," and "no" categories for removability. Although only 14.0% were categorized, 83.6% of patients received at least one analyzable drug. Among them, 83.8% had at least one potentially removable drug. Real-world data highlights the need for caution in drug treatments during TPE to ensure optimal therapeutic outcomes, particularly for specific drugs.

Synthesis and Neurobehavioral Evaluation of a Potent Multitargeted Inhibitorfor the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) poses a significant health challenge worldwide, affecting millions of individuals, and projected to increase further as the global population ages. Current pharmacological interventions primarily target acetylcholine deficiency and amyloid plaque formation, but offer limited efficacy and are often associated with adverse effects. Given the multifactorial nature of AD, there is a critical need for novel therapeutic approaches that simultaneously target multiple pathological pathways. Targeting key enzymes involved in AD pathophysiology, such as acetylcholinesterase, butyrylcholinesterase, beta-site APP cleaving enzyme 1 (BACE1), and gamma-secretase, is a potential strategy to mitigate disease progression. To this end, our research group has conducted comprehensive in silico screening to identify some lead compounds, including IQ6 (SSZ), capable of simultaneously inhibiting the enzymes mentioned above. Building upon this foundation, we synthesized SSZ, a novel multitargeted ligand/inhibitor to address various pathological mechanisms underlying AD. Chemically, SSZ exhibits pharmacological properties conducive to AD treatment, featuring pyrrolopyridine and N-cyclohexyl groups. Preclinical experimental evaluation of SSZ in AD rat model showed promising results, with notable improvements in behavioral and cognitive parameters. Specifically, SSZ treatment enhanced locomotor activity, ameliorated gait abnormalities, and improved cognitive function compared to untreated AD rats. Furthermore, brain morphological analysis demonstrated the neuroprotective effects of SSZ, attenuating Aβ-induced neuronal damage and preserving brain morphology. Combined treatment of SSZ and conventional drugs (DON and MEM) showed synergistic effects, suggesting a potential therapeutic strategy for AD management. Overall, our study highlights the efficacy of multitargeted ligands like SSZ in combating AD by addressing the complex etiology of the disease. Further research is needed to elucidate the full therapeutic potential of SSZ and the exploration of similar compounds in clinical settings, offering hope for an effective AD treatment in the future.

Antibiotic-Loaded Nano-Sized Delivery Systems: An Insight into Gentamicin and Vancomycin

The fight against infectious disease has remained an ever-evolving challenge in the landscape of healthcare. The ability of pathogens to develop resistance against conventional drug treatments has decreased the effectiveness of therapeutic interventions, and antibiotic resistance is recognized as one of the main challenges of our time. The goal of this systematic review paper is to provide insight into the research papers published on innovative nanosized drug delivery systems (DDSs) based on gentamycin and vancomycin and to discuss the opportunity of their repurposing through nano DDS formulations. These two antibiotics are selected because (i) gentamicin is the first-line drug used to treat suspected or confirmed infections caused by Gram-negative bacterial infections and (ii) vancomycin is used to treat serious Gram-positive bacterial infections. Moreover, both antibiotics have severe adverse effects, and one of the purposes of their formulation as nanosized DDSs is to overcome them. The review paper includes an introduction focusing on the challenges of infectious diseases and traditional therapeutic treatments, a brief description of the chemical and pharmacological properties of gentamicin and vancomycin, case studies from the literature on innovative nanosized DDSs as carriers of the two antibiotic drugs, and a discussion of the results found in the literature.

EC-IC bypass for occlusion of the internal carotid artery

There are barely any alternative treatment options to the drug treatment of hemodynamically caused cerebral ischemia, as in occlusion of the internal carotid artery. For secondary prevention of an ischemic stroke due to carotid occlusion and hemodynamic instability, extracranial-intracranial (EC-IC) bypass surgery can be an important option in selected patients. The development, study situation, indications and surgical technique for placement of an EC-IC bypass in cases of occlusion of the internal carotid artery are presented. With appropriate expertise and strict selection of patients, the placement of an EC-IC bypass enables stabilization of cerebral perfusion with a low rate of complications. The study situation is controversially discussed; nevertheless, surgical treatment in a specialized neurovascular center should at least be considered.

Early clinical response associates with long-term outcomes with ixekizumab in radiographic axial spondyloarthritis

BackgroundThe Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at...

The Thorny Intersection Between Adult Drug Treatment Courts and Medical Marijuana Criminal Immunity Laws

Two revolutionary developments impacted the United States criminal justice system over the past 30 years that are now primed for an institutional reckoning—the legalization of medical marijuana at the state level and the exponential rise of adult drug treatment courts across the country. The states that have legalized medical marijuana also provide criminal immunity protections for qualifying medical marijuana patients, including those serving probationary sentences. Drug treatment courts are a form of intensive probation offering treatment services for participants plagued by substance use disorders. Most drug treatment courts operate on an abstinence‐based model and do not permit the use of medical marijuana. Consequently, challenges by drug court participants to the continued prohibition of medical marijuana are on the horizon. The purpose of this article is to highlight the contours of these knotty issues from a sociolegal perspective. The material for this article stems from a review of existing judicial decisions in addition to qualitative data collected during my case studies of three different adult drug treatment courts.

Pharmacogenomics: A Genetic Approach to Drug Development and Therapy

The majority of the well-known pharmacogenomics research used in the medical sciences contributes to our understanding of medication interactions. It has a significant impact on treatment and drug development. The broad use of pharmacogenomics is required for the progress of therapy. The main focus is on how genes and an intricate gene system affect the body’s reaction to medications. Novel biomarkers that help identify a patient group that is more or less likely to respond to a certain medication have been discovered as a result of recent developments in the field of clinical therapeutics. It aims to improve customized therapy by giving the appropriate drug at the right dose at the right time and making sure that the right prescriptions are issued. A combination of genetic, environmental, and patient variables that impact the pharmacokinetics and/or pharmacodynamics of medications results in interindividual variance in drug response. Drug development, illness susceptibility, and treatment efficacy are all impacted by pharmacogenomics. The purpose of this work is to give a review that might serve as a foundation for the creation of new pharmacogenomics applications, techniques, or strategies.

Suppression of CTC1 inhibits hepatocellular carcinoma cell growth and enhances RHPS4 cytotoxicity.

Although DNA repair mechanisms function to maintain genomic integrity, in cancer cells these mechanisms may negatively affect treatment efficiency. The strategy of targeting cancer cells via inhibiting DNA damage repair has been successfully used in breast and ovarian cancer using PARP inhibitors. Unfortunately, such strategies have not yet yielded results in liver cancer. Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a treatment-resistant malignancy. Despite the development of guided therapies, treatment regimens for advanced HCC patients still fall short of the current need and significant problems such as cancer relapse with resistance still exist. In this paper, we targeted telomeric replication protein CTC1, which is responsible for telomere maintenance. CTC expression was analyzed using tumor and matched-tissue RNA-sequencing data from TCGA and GTEx. In HCC cell lines, q-RT-PCR and Western blotting were used to detect CTC1 expression. The knock-down of CTC1 was achieved using lentiviral plasmids. The effects of CTC1 silencing on HCC cells were analyzed by flow cytometry, MTT, spheroid and colony formation assays. CTC1 is significantly downregulated in HCC tumor samples. However, CTC1 protein levels were higher in sorafenib-resistant cell lines compared to the parental groups. CTC1 inhibition reduced cell proliferation in sorafenib-resistant HCC cell lines and diminished their spheroid and colony forming capacities. Moreover, these cells were more sensitive to single and combined drug treatment with G4 stabilizer RHPS4 and sorafenib. Our results suggest that targeting CTC1 might be a viable option for combinational therapies designed for sorafenib resistant HCC patients.

Hot Water Epilepsy with Alone and Spontaneous Seizures in Childhood

ObjectivesHot water epilepsy (HWE) is a type of epilepsy that primarily affects children. This study was aimed to evaluate the clinical, electroencephalogram (EEG), neuroimaging findings, and treatment options in children with HWE. MethodsThe medical records of 24 patients who had HWE were evaluated retrospectively. ResultsThere were 2767 patients diagnosed with epilepsy during the seven-year period, and 0.86% of the patients had HWE. The median age of the patients was three (range 1.2-7 years), with a male predominance (male/female ratio: 7.1). Six patients (25%) had HWE with spontaneous seizures (HWESS) and 18 patients (75%) had HWE alone (HWEA). 11 patients had focal onset seizures, 13 patients had generalized onset seizures. EEG abnormalities were found in 7 patients (29.2%). Three patients (12.5%) had nonspecific MRI findings. Developmental abnormalities (autism spectrum disorder, learning disability and speech disturbance.) were detected in 8 patients (33.3%). Only one patient's (4.2%) seizure could be controlled by changing bathroom habits. Twenty-three patients (95.8%) were given antiepileptic drugs. 18 of 24 patients had come for follow-up visits for two years, nine of them used monotherapy and seizures did not recur. The treatment response was 55.5%. Oxcarbazepine (8 patients, 33.3%) and valproic acid (7 patients, 29.2%) were the most chosen two drugs for HWE. The genetic tests performed were not accepted relevant to the patients' clinical conditions and epilepsy. ConclusionThe frequency of the HWE was not as high in the literature. Male predominance, EEG abnormalities may be seen. Changing bath room habits did not improve the treatment as a first line management, all the patients except one used antiepileptic drug treatment. Until now, there has been no study in Turkey showing the frequency of HWE exclusively in children.