Energy, exergy, environmental, and economic (4E) analyses of the usability of various nano-sized particles added lubricant in a heat pump system.

The need for energy is rising significantly with the growth of technology in the world. This energy need is largely met by fossil fuels. The enhancement in their prices and the damage they induce to the environment, scientists have turned to alternative energy sources due to the depletion of fossil fuels. In recent years, these alternative energy sources have come to the fore as solar, wind, and wave energy. However, heating and refrigeration systems, whose share of energy consumption in buildings in the world is 40 %, can also compete with these alternative energy sources. In particular, heat pumps (HP) are at a level that can compete with renewable energy sources to seriously reduce this rate. In this study, different nanoparticles were added to the Polyol ester oil (POE) utilized in the compressor to enhance the performance of the HP. Thermodynamic, environmental, and economic performances of the obtained nanolubricants at different concentrations (0.5 wt% and 1 wt%) and flow rates (15, 30, and 45 g/s) were evaluated. The highest COP value of the HP was calculated as 4.14 at 0.5 wt% B-POE at 45 g/s. The best energy consumption in the HP was obtained with 0.5 wt% B-POE nanolubricant with a decrease of 10.96 % at 45 g/s compared to pure POE. The highest exergy efficiency in the HP was calculated at 0.5 wt% B-POE nanolubricant with a 13.53 % increase at 30 g/s compared to pure POE. The best exergoeconomic parameter ( R g , e x ) performance was determined as 3.7148 kWh/$ in 1 wt% TiO2-POE nanolubricant at 45 g/s. The best enviro-economic value of 0.16182 ¢/h was obtained with 0.5 wt% B-POE nanolubricant at 45 g/s. In line with the results obtained, it was observed that the B-POE nanolubricant has a performance that can compete with the good-performing TiO2-POE nanolubricant.

Prevalence of priformis syndrome in sciatica patients: Predictability of specific tests and radiological findings for diagnosis.

Background: The traditional approach for diagnosing piriformis syndrome (PS) is to rule out other causes of sciatica. This approach may lead to unnecessary radiological examinations and a waste of time. In contrast to the traditional approach, we aimed to first exclude PS and determine its prevalence by injecting patients with priformis tenderness. Methods: This observational cross-sectional study included patients diagnosed with PS who had sciatica and tenderness on palpation of the priformis muscle and whose pain was reduced by at least 50% with local injection. Age, sex, pain duration, presence of tenderness in the piriformis muscle, Freiberg test, PACE sign, FADIR, Visual Analog Scale (VAS) score, Douleur Neuropathique 4 Questions (DN4) score, and radiological findings were compared between patients who responded and those who did not respond to the priformis injection. Results: A total of 110 patients with sciatica were evaluated, of whom 66 with tenderness on palpation of the primiformis muscle underwent local injection. In 27 of the 66 patients (40.9%), a decrease in the NRS score of >50% was observed after injection, and PS was diagnosed. There were no statistically significant differences in age, sex, pain duration, Pace, FADIR test positivity, radiological findings, NRS, and DN4 scores, but Freiberg test positivity was statistically higher in patients diagnosed with PS. Conclusion: PS is more common than is thought to be a cause of sciatica. A positive Freiberg test is predictive for the diagnosis of PS, but it should be confirmed by tenderness of the priformis muscle and local injection. Many pathologies can be detected incidentally radiographically in PS; however, they are not predictive of the diagnosis.

Evaluation of the efficacy of ultrasound-guided maxillary and mandibular nerve pulsed radiofrequency treatment for trigeminal neuralgia and factors associated with successful response: a retrospective study.

BACKGROUND: This study aimed to investigate the treatment efficacy and clinical and demographic characteristics affecting treatment success in patients who underwent ultrasound (US)-guided pulsed radiofrequency (PRF) to the maxillary and/or mandibular nerves for trigeminal neuralgia. METHODS: The data of patients with trigeminal neuralgia who underwent US-guided maxillary and/or mandibular nerve PRF between September 2022 and December 2023 were reviewed and the study was retrospectively designed. Good analgesia was defined as ≥ 50% reduction in pain score at 3 months after the procedure, and the demographic and clinical characteristics of the patients were assessed. RESULTS: Among the 72 included patients, 39 (54.2%) and 33 (45.8%) were classified as responders and non-responders, respectively. The age, pre- and post-procedural Numerical Rating Scale (NRS) scores, pain duration, and presence of constant pain were significantly lower in the responders. Logistic regression analysis revealed that older age (OR = 0.899, p < 0.001), high pre-procedural NRS scores (OR = 0.177, p = 0.009) and non-idiopathic (secondary or classic) etiology (OR = 0.062, p = 0.048) were significantly associated with an unsuccessful response to maxillary/mandibular PRF treatment. CONCLUSION: This study is the first clinical trial to evaluate the efficacy of PRF therapy of the maxillary and mandibular nerves in the treatment of trigeminal neuralgia and demonstrated a significant reduction in pain scores at 3 months. Older age, high pre-procedural NRS scores, and non-idiopathic (secondary or classical) etiology are independent predictors of poor response to ultrasound-guided maxillary/mandibular nerve pulse radiofrequency treatment.

A Comparison Between the Efficacy of Trigeminal Ganglion Radiofrequency Thermocoagulation and Ultrasound-Guided Maxillary-Mandibular Nerve Pulsed Radiofrequency in the Treatment of Trigeminal Neuralgia: A Randomized Clinical Trial.

Background and objective Trigeminal neuralgia (TN) is a debilitating disorder characterized by acute episodic attacks of pain that significantly impair patients' quality of life and overall functioning. Initial therapeutic strategies to treat this condition include pharmacological options, particularly carbamazepine. In cases with resistance to dose escalation and polypharmacy, interventional procedures may be warranted. The primary aim of this study was to compare the efficacy of trigeminal ganglion (TG) radiofrequency thermocoagulation (RFT) and ultrasound (US)-guided maxillary/mandibular (max/mand) nerve pulsed radiofrequency (PRF) for treating TN, based on the findings at six months post-treatment. The secondary aims were to assess the impact of these interventions on drug consumption and interventional safety based on adverse events. Methods This prospective, randomized, single-blind study was conducted at a single pain clinic. Forty-four patients were randomized into two groups. Group RFT received TG RFT at 60 °C, 65 °C, and 70 °C for 60 seconds each, whereas Group PRF received max/mand PRF for 240 seconds. Pain relief was assessed by using the numeric rating scale (NRS) and intervention effectiveness on medication consumption was evaluated by using the Medication Quantification Scale III (MQS III). The rates of intervention-related adverse events were also compared. Results Both RFT and PRF significantly alleviated pain at one and six months post-treatment compared to baseline (p<0.05). No statistical differences were found in the NRS and MQS III scores between the groups. At six months, 77.3% of RFT patients and 63.9% of PRF patients experienced at least 50% pain relief, with no statistically significant difference. Hypoesthesia occurred in two RFT patients, and masseter weakness was observed in one patient, while no adverse events were reported in the PRF group. Conclusions TG RFT and max/mand PRF are effective treatments for TN. US-guided max/mand PRF, which avoids RFT-associated complications and radiation exposure, may be the superior and preferable option. In this study, the potential space between the coronoid process and maxilla was used to access the maxillary nerve during the maxillary block and PRF procedures, in contrast to the classical approach through the mandibular notch. Further large-scale randomized controlled trials are required to gain deeper insights into the topic.

Application of the full consistency method (FUCOM) - Cosine similarity framework in 5G infrastructure investment planning: An approach for telecommunication quality improvements.

In the rapidly evolving telecommunications landscape, the shift towards advanced communication technologies marks a critical milestone. This transition promises to revolutionize connectivity by enabling seamless data downloads, high-quality video streaming, and instant access to applications. However, adapting to these advanced technologies poses significant challenges for infrastructure expansion, requiring innovative investment and deployment strategies. These strategies aim not only to enhance service quality but also to ensure extensive network coverage. To address the need for systematic planning in infrastructure investment, this paper presents a novel methodology that combines the Full Consistency Method (FUCOM) with cosine similarity analysis. This integrated approach effectively prioritizes service areas for the deployment of 5G technology, emphasizing the importance of detailed planning in mobile strategy development. By leveraging FUCOM to determine the weights of various criteria and employing cosine similarity analysis to rank service areas, the methodology facilitates efficient resource allocation and service quality enhancements. Empirical validation using real data from a Turkish telecommunications company confirmed the effectiveness of the proposed algorithm. The results indicate that this integrated approach can significantly advance the telecommunications industry by providing essential insights for companies seeking to improve service quality amidst the transition to 5G and beyond. The successful implementation of the proposed algorithm demonstrates its effectiveness in addressing the challenges faced by telecommunications companies and underscores the importance of a data-driven approach in strategic decision-making and resource allocation. Furthermore, the findings suggest that the integrated FUCOM and cosine similarity analysis approach can offer a valuable tool for telecommunications companies worldwide, offering a systematic method for prioritizing infrastructure investments and enhancing network performance.

Comparison of tibial nerve pulsed radiofrequency and intralesional radiofrequency thermocoagulation in the treatment of painful calcaneal spur and plantar fasciitis: a randomized clinical trial.

OBJECTIVE: Ultrasound-guided tibial nerve pulsed radiofrequency (US-guided TN PRF) and fluoroscopy-guided intralesional radiofrequency thermocoagulation (FL-guided intralesional RFT) adjacent to the painful calcaneal spur are two interventions for pain management in painful calcaneal spur and plantar fasciitis. This study aimed to compare the effectiveness of the two procedures. DESIGN: A prospective, randomized, single-blind study. SETTING: Single-center pain clinic. SUBJECTS: Forty-nine patients who met the inclusion criteria were randomized into two groups. METHODS: Group U (25 patients) received US-guided TN PRF at 42°C for 240 s, whereas Group F (24 patients) received FL-guided intralesional RFT at 80°C for 90 s. The most severe numeric rating scale (NRS) score during the first morning steps and the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores were used to evaluate the effectiveness of the procedures. The study's primary outcome assessed treatment effectiveness via the NRS, whereas the secondary outcomes included changes in the AOFAS score and the incidence of procedure-related mild adverse events. RESULTS: NRS and AOFAS scores significantly improved in Groups U and F at 1 and 3 months compared with baseline (P < .05), and there was no significant difference between the groups. At month 1, 50% or greater pain relief was achieved in 72% of patients in Group U and 75% of patients in Group F. No significant difference was observed in the incidence of mild adverse events between the groups. CONCLUSIONS: US-guided TN PRF and FL-guided intralesional RFT have shown significant effectiveness in the treatment of painful calcaneal spur and plantar fasciitis. Larger randomized controlled trials are needed. CLINICAL TRIAL NUMBER: NCT06240507.

Comparison of Selective Nerve Root Pulsed Radiofrequency Vs Paramedian Interlaminar Epidural Steroid Injection for the Treatment of Painful Cervical Radiculopathy.

BACKGROUND: Although there are studies evaluating ultrasound-guided selective nerve root pulsed radiofrequency (ULSD-SNRPRF) and fluoroscopy-guided paramedian cervical interlaminar epidural steroid injection (FL-CIESI) for the treatment of chronic cervical radicular pain, no study has compared the efficacy of these 2 methods. OBJECTIVES: This study aimed to compare the efficacy of these 2 methods, their superiority to each other, and the incidence of adverse events. STUDY DESIGN: A prospective, randomized controlled trial. SETTING: Outpatient department of a single-center pain clinic. METHODS: Sixty patients who did not respond to conservative treatments for lower cervical radicular pain were randomly divided into 2 groups. One group underwent ULSD-SNRPRF (Group U), and the other underwent paramedian FL-CIESI (Group F). Patients were evaluated pretreatment, and 3 and 6 months posttreatment. The Numeric Rating Scale (NRS-11) was used to assess clinical improvement, The Neck Disability Index (NDI) to assess improvement in functional disability, and the Self-Leeds Assessment of Neuropathic Symptoms and Signs Pain Score (S-LANSS) to assess the treatment's effect on neuropathic pain. Clinically significant pain relief was defined as a 50% or more pain reduction in the NRS-11. The posttreatment reduction in medication consumption was assessed using the Medication Quantification Scale Version III (MQS III). We also evaluated whether there was a difference in treatment-related characteristics, such as procedure time and adverse events. RESULTS: The procedure time was significantly longer in Group U. Blood aspiration was observed in 2 patients in Group U and vascular spread in one patient in Group F, with no significant difference. At 3 and 6 months posttreatment, NRS-11 and NDI scores showed a significant decrease compared to the pretreatment scores in both groups; there was no difference between the groups. Both treatments effectively improved neuropathic pain, with no significant difference between the S-LANSS scores. There was no difference in the reduction of medication consumption between the groups. LIMITATIONS: There was no sham or control group, and the follow-up period was limited to 6 months. CONCLUSIONS: Pain relief, functional improvement, and safety were similar between groups. ULSD-SNRPRF and paramedian FL-CIESI are 2 different effective techniques for chronic cervical radicular pain. The choice of method should depend on various factors, such as patient preference, operator experience, and availability of resources. An advantage of ULSD over fluoroscopy is that patients and physicians are not exposed to radiation.

Evaluation of the efficacy of pulsed radiofrequency therapy in patients with lumbosacral radicular pain: An analysis of single-center data.

OBJECTIVES: Lumbosacral radicular pain (LRP) is one of the most common causes of neuropathic pain. This pain often arises from inflammation in the dorsal root ganglia (DRG) or spinal nerves. Despite various treatment modalities, success rates are not very high in chronic LRP cases. Pulsed radiofrequency (PRF) therapy, frequently applied to the DRG, is widely used, but its effectiveness is often questioned in various studies. The primary aim of our study is to evaluate the effectiveness of PRF treatment in 154 patients. METHODS: Patients with LRP for longer than 3 months, treated with PRF, were included in this study. To assess the efficacy of PRF treatment, numerical rating scale (NRS) scores were evaluated at the 4th-week and 6th-month follow-ups. RESULTS: The NRS scores were significantly lower at the 4th-week and 6th-month follow-ups compared to pre-treatment levels (p<0.001). However, there was no significant difference between the mean NRS scores at the 4th week and 6th month. CONCLUSION: Success in interventional pain procedures is often considered as at least a 50% reduction in pain scores. The success rate for PRF treatment for LRP in the literature varies between 30% and 60%, which is similar to our findings at the 4th week and 6th month. PRF treatment is widely used due to its low side-effect profile and cost-effectiveness in the long term. There is no fully standardized practice regarding procedural aspects, such as the duration of the application, and prospective studies with larger participation are needed.

Ultrasound-Guided Coccygeal Nerve Radiofrequency Ablation and Steroid Injection: Combination Therapy for Coccydynia.

OBJECTIVES: Coccydynia is characterized by pain in tailbone region, which affects the quality of life. Various interventional procedures are performed for coccydynia that is unresponsive to conservative treatment. This study aimed to evaluate the efficacy of ultrasound (US)-guided radiofrequency ablation (RFA) and steroid injection of the coccygeal nerve in patients with idiopathic and traumatic coccydynia. METHODS: In this prospective study, 32 patients with coccydynia unresponsive to conservative treatments underwent US-guided RFA of the coccygeal nerve. Coccygeal nerves were visualized at the level of the coccygeal cornua with US, 1 mL lidocaine 2% was injected into both areas and radiofrequency ablation was performed at 90°C for 60 seconds. After RFA, 2 mL dexamethasone and 2 mL bupivacaine 0.5% were injected. Visual Analog Scale (VAS) and Paris scales were used to evaluate the effect of treatment on pain and functionality before and at 1, 4, and 12 weeks after treatment. RESULTS: We found that 54% of the patients had a >50% reduction in VAS score and 66% of the patients had a >50% reduction in Paris scores measured between baseline and week 12. Additionally, the main effect of time on the VAS and Paris scores was statistically significant (P < .001) in all measurements. Baseline P and VAS scores were higher than the post-treatment measurements (P < .001). CONCLUSIONS: Our study showed that US-guided steroid injection and RFA of the coccygeal nerve for chronic coccydynia significantly improved pain and function scores at weeks 1, 4, and 12. RFA also results in a lower rate of adverse events. This study is the first clinical trial of ultrasound-guided coccygeal nerve RFA in patients with coccydynia. We believe that this new less invasive method may be an alternative to other interventional treatments.

A new neuromodulation method in chronic migraine; non-invasive pulsed radiofrequency, a single-blinded, randomised, controlled trial.

OBJECTIVE: Non-invasive pulsed radiofrequency (NipRF) therapy, a neuromodulation method for peripheral nerves, is a new treatment modality for pain. We aimed to show the changes in pain severity and frequency per month in chronic migraine with NipRF treatment. METHODS: We treated patients diagnosed with chronic migraine according to the International Classification of Headache Disorders III beta diagnostic criteria. In half of the patients, we applied pulsed radiofrequency (pRF) treatment with transcutaneous electrodes to the greater occipital nerve (GON) trace. In the other half, we applied the GON block under ultrasound guidance. The Migraine Disability Assessment Scale (MIDAS) was administered to the participants, and those with scores > 2 were included in the study. Pain intensity and frequency were evaluated using the visual analog scale (VAS) and a headache diary completed before and 4 weeks after treatment. RESULTS: When both groups were compared, the pre- and post-treatment VAS scores and headache frequencies were similar. Comparing the pre-treatment and post-treatment values within the groups, VAS scores and headache frequency decreased significantly after treatment in both groups (p < 0.001). CONCLUSION: In this study, we observed that NipRF treatment is safe and effective for treating chronic migraine. Pain intensity and frequency decreased with NipRF treatment, similar to that in the GON block group. CLINICAL TRIALS REGISTRATION NUMBER: NCT05499689, Date: 08/11/2022.

Parasagittal Interlaminar and Transforaminal Epidural Steroid Injections for Radicular Low Back Pain; Which is More Comfortable?

Objective: This study aimed to compare parasagittal interlaminar (PS) and transforaminal (TF) epidural steroid injections for unilateral L5 and S1 radicular lower back pain in terms of patient comfort, efficacy, safety, contrast enhancement, and radiation exposure. Methods: This was a prospective randomized single-blind study. A total of 59 participants were included in this study. The visual analog scale (VAS) and Oswestry Disability Index (ODI) were obtained. A comfort questionnaire was administered to all participants. The total fluoroscopy time and contrast distribution levels were recorded. Results: Pre- and post-treatment VAS scores were similar between the groups. The ODI scores increased in favor of the PS group at week 2 (P < 0.041); however, there was no difference between the two groups at other times. The VAS and ODI scores improved significantly with treatment in both the groups (P < 0.001). Total fluoroscopy time was shorter in the PS group (P < 0.001). PS application was more comfortable (P < 0.001). While no complications were observed in the PS group, three complications occurred in the TF group. Anterior epidural contrast spread to three or more levels was observed in 57% of the participants in the PS group, whereas no spread to more than two levels was observed in the TF group. Conclusion: The PS epidural approach is superior to the TF approach in terms of a low incidence of side effects, less radiation exposure, better patient comfort, higher epidural contrast spread, and single-level needle access.

Comparison of the efficacy of genicular nerve phenol neurolysis and radiofrequency ablation for pain management in patients with knee osteoarthritis.

Background: : Genicular nerve neurolysis with phenol and radiofrequency ablation (RFA) are two interventional techniques for treating chronic refractory knee osteoarthritis (KOA) pain. This study aimed to compare the efficacy and adverse effects of both techniques. Methods: : Sixty-four patients responding to diagnostic blockade of the superior medial, superior lateral, and inferior medial genicular nerve under ultrasound guidance were randomly divided into two groups: Group P (2 mL phenol for each genicular nerve) and Group R (RFA 80°C for 60 seconds for each genicular nerve). The numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to evaluate the effectiveness of the interventions. Results: : RFA and phenol neurolysis of the genicular nerves provided effective analgesia within groups at 1 week, 1 month, and 3 months compared to baseline. There was no significant difference between the groups in terms of NRS and WOMAC scores at all measurement times. At the 3rd month follow-up, 50% or more pain relief was observed in 53.1% of patients in Group P and 50% of patients in Group R. The rate of transient paresthesia was 34.4% in Group P and 6.3% in Group R, and this was significantly higher in Group P. Conclusions: : Neurolysis of the genicular nerves with both RFA and phenol is effective in the management of KOA pain. Phenol may be a good alternative to RFA. Further studies are needed on issues such as dose adjustment to prevent transient paresthesia response.

A state of art review on estimation of solar radiation with various models.

Solar radiation is free, and very useful input for most sectors such as heat, health, tourism, agriculture, and energy production, and it plays a critical role in the sustainability of biological, and chemical processes in nature. In this framework, the knowledge of solar radiation data or estimating it as accurately as possible is vital to get the maximum benefit from the sun. From this point of view, many sectors have revised their future investments/plans to enhance their profit margins for sustainable development according to the knowledge/estimation of solar radiation. This case has noteworthy attracted the attention of researchers for the estimation of solar radiation with low errors. Accordingly, it is noticed that various types of models have been continuously developed in the literature. The present review paper has mainly centered on the solar radiation works estimated by the empirical models, time series, artificial intelligence algorithms, and hybrid models. In general, these models have needed the atmospheric, geographic, climatic, and historical solar radiation data of a given region for the estimation of solar radiation. It is seen from the literature review that each model has its advantages and disadvantages in the estimation of solar radiation, and a model that gives the best results for one region may give the worst results for the other region. Furthermore, it is noticed that an input parameter that strongly improves the performance success of the models for a region may worsen the performance success of another region. In this direction, the estimation of solar radiation has been separately detailed in terms of empirical models, time series, artificial intelligence algorithms, and hybrid algorithms. Accordingly, the research gaps, challenges, and future directions for the estimation of solar radiation have been drawn in the present study. In the results, it is well-observed that the hybrid models have exhibited more accurate and reliable results in most studies due to their ability to merge between different models for the benefit of the advantages of each model, but the empirical models have come to the fore in terms of ease of use, and low computational costs.

Effect of neuropathic pain on sphenopalatine ganglion block responses in persistent idiopathic facial pain.

OBJECTIVES: Management of persistent idiopathic facial pain (PIFP) can be challenging. Sphenopalatine ganglion (SPG) has been the target for the interventional treatment of many facial pain syndromes. However, possible factors that may affect SPG block success are unknown. It was aimed to investigate the effect of neuropathic pain on SPG block outcomes in PIFP, which includes a heterogeneous patient group. METHODS: All of the patients underwent fluoroscopy-guided SPG block with an injection of 40 mg of 2% lidocaine and 8 mg of dexamethasone. The patients were assigned to 2 groups according to existence of neuropathic pain determined with the DN4 questionnaire score: 19 patients with neuropathic pain (Group 1) and 15 patients without neuropathic pain (Group 2). Preprocedural and postprocedural Visual Analog Scale (VAS) scores were compared between the 2 groups. RESULTS: The mean age of the patients was 47.65 ± 6.50 years. The average pain duration was 52.95 ± 34.81 weeks. A significantly greater decrease was detected in the VAS scores at 1 week (p = 0.036) and 1 month (p < 0.001) in Group 1 when compared to Group 2. Moreover, the proportion of patients with >50% improvement in the VAS scores at 1 week (p = 0.012) and 1 month (P = 0.017) was significantly lower in Group 1 than in Group 2. DISCUSSION: SPG block appears as a safe, effective, and rapid method to treat PIFP, especially in cases with neuropathic pain. Neuropathic pain may be a predictor for pain relief in interventional procedures targeting SPG in the treatment of PIFP.

A novel homozygous RIPK4 variant in a family with severe Bartsocas-Papas syndrome.

Bartsocas-Papas syndrome (BPS) is a rare autosomal recessive disorder characterized by popliteal pterygia, syndactyly, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and genital malformations. Most of the BPS cases reported to date are fatal either in the prenatal or neonatal period. Causative genetic defects of BPS were mapped on the RIPK4 gene encoding receptor-interacting serine/threonine kinase 4, which is critical for epidermal differentiation and development. RIPK4 variants are associated with a wide range of clinical features ranging from milder ectodermal dysplasia to severe BPS. Here, we evaluated a consanguineous Turkish family, who had two pregnancies with severe multiple malformations compatible with BPS phenotype. In order to identify the underlying genetic defect, direct sequencing of the coding region and exon-intron boundaries of RIPK4 was carried out. A homozygous transversion (c.481G>C) that leads to the substitution of a conserved aspartic acid to histidine (p.Asp161His) in the kinase domain of the protein was detected. Pathogenicity predictions, molecular modeling, and cell-based functional assays showed that Asp161 residue is required for the kinase activity of the protein, which indicates that the identified variant is responsible for the severe BPS phenotype in the family.

TAp73ß Can Promote Hepatocellular Carcinoma Dedifferentiation.

Hepatocyte dedifferentiation is a major source of hepatocellular carcinoma (HCC), but its mechanisms are unknown. We explored the p73 expression in HCC tumors and studied the effects of transcriptionally active p73ß (TAp73ß) in HCC cells. Expression profiles of p73 and patient clinical data were collected from the Genomic Data Commons (GDC) data portal and the TSVdb database, respectively. Global gene expression profiles were determined by pan-genomic 54K microarrays. The Gene Set Enrichment Analysis method was used to identify TAp73ß-regulated gene sets. The effects of TAp73 isoforms were analyzed in monolayer cell culture, 3D-cell culture and xenograft models in zebrafish using western blot, flow cytometry, fluorescence imaging, real-time polymerase chain reaction (RT-PCR), immunohistochemistry and morphological examination. TAp73 isoforms were significantly upregulated in HCC, and high p73 expression correlated with poor patient survival. The induced expression of TAp73ß caused landscape expression changes in genes involved in growth signaling, cell cycle, stress response, immunity, metabolism and development. Hep3B cells overexpressing TAp73ß had lost hepatocyte lineage biomarkers including ALB, CYP3A4, AFP, HNF4α. In contrast, TAp73ß upregulated genes promoting cholangiocyte lineage such as YAP, JAG1 and ZO-1, accompanied with an increase in metastatic ability. Our findings suggest that TAp73ß may promote malignant dedifferentiation of HCC cells.

Finding underlying genetic mechanisms of two patients with autism spectrum disorder carrying familial apparently balanced chromosomal translocations.

BACKGROUND: Genetic etiologies of autism spectrum disorders (ASD) are complex, and the genetic factors identified so far are very diverse. In complex genetic diseases such as ASD, de novo or inherited chromosomal abnormalities are valuable findings for researchers with respect to identifying the underlying genetic risk factors. With gene mapping studies on these chromosomal abnormalities, dozens of genes have been associated with ASD and other neurodevelopmental genetic diseases. In the present study, we aimed to idenitfy the causative genetic factors in patients with ASD who have an apparently balanced chromosomal translocation in their karyotypes. METHODS: For mapping the broken genes as a result of chromosomal translocations, we performed whole genome DNA sequencing. Chromosomal breakpoints and large DNA copy number variations (CNV) were determined after genome alignment. Identified CNVs and single nucleotide variations (SNV) were evaluated with VCF-BED intersect and Gemini tools, respectively. A targeted resequencing approach was performed on the JMJD1C gene in all of the ASD cohorts (220 patients). For molecular modeling, we used a homology modeling approach via the SWISS-MODEL. RESULTS: We found that there was no contribution of the broken genes or regulator DNA sequences to ASD, whereas the SNVs on the JMJD1C, CNKSR2 and DDX11 genes were the most convincing genetic risk factors for underlying ASD phenotypes. CONCLUSIONS: Genetic etiologies of ASD should be analyzed comprehensively by taking into account of the all chromosomal structural abnormalities and de novo or inherited CNV/SNVs with all possible inheritance patterns.

RIPK4 suppresses the TGF-ß1 signaling pathway in HaCaT cells.

Receptor-interacting serine/threonine kinase 4 (RIPK4) and transforming growth factor-ß 1 (TGF-ß1) play critical roles in the development and maintenance of the epidermis. A negative correlation between the expression patterns of RIPK4 and TGF-ß signaling during epidermal homeostasis-related events and suppression of RIPK4 expression by TGF-ß1 in keratinocyte cell lines suggest the presence of a negative regulatory loop between the two factors. So far, RIPK4 has been shown to regulate nuclear factor-κB (NF-κB), protein kinase C (PKC), wingless-type MMTV integration site family (Wnt), and (mitogen-activated protein kinase) MAPK signaling pathways. In this study, we examined the effect of RIPK4 on the canonical Smad-mediated TGF-ß1 signaling pathway by using the immortalized human keratinocyte HaCaT cell line. According to our results, RIPK4 inhibits intracellular Smad-mediated TGF-ß1 signaling events through suppression of TGF-ß1-induced Smad2/3 phosphorylation, which is reflected in the upcoming intracellular events including Smad2/3-Smad4 interaction, nuclear localization, and TGF-ß1-induced gene expression. Moreover, the kinase activity of RIPK4 is required for this process. The in vitro wound-scratch assay demonstrated that RIPK4 suppressed TGF-ß1-mediated wound healing through blocking TGF-ß1-induced cell migration. In conclusion, our results showed the antagonistic effect of RIPK4 on TGF-ß1 signaling in keratinocytes for the first time and have the potential to contribute to the understanding and treatment of skin diseases associated with aberrant TGF-ß1 signaling.

Integrated multi-omics data analysis identifying novel drug sensitivity-associated molecular targets of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third-leading cause of malignancy-associated mortality worldwide. HCC cells are highly resistant to chemotherapeutic agents. Therefore, there are currently only two US Food and Drug Administration-approved drugs available for the treatment of HCC. The objective of the present study was to analyze the results of previously published high-throughput drug screening, and in vitro genomic and transcriptomic data from HCC cell lines, and to integrate the obtained results to define the underlying molecular mechanisms of drug sensitivity and resistance in HCC cells. The results of treatment with 225 different small molecules on 14 different HCC cell lines were retrieved from the Genomics of Drug Sensitivity in Cancer database and analyzed. Cluster analysis using the treatment results determined that HCC cell lines consist of two groups, according to their drug response profiles. Continued analyses of these two groups with Gene Set Enrichment Analysis method revealed 6 treatment-sensitive molecular targets (epidermal growth factor receptor, mechanistic target of rapamycin, deoxyribonucleic acid-dependent protein kinase, the Aurora kinases, Bruton's tyrosine kinase and phosphoinositide 3-kinase; all P<0.05) and partially effective drugs. Genetic and genome-wide gene expression data analyses of the determined targets and their known biological partners revealed 2 somatically mutated and 13 differentially expressed genes, which differed between drug-resistant and drug-sensitive HCC cells. Integration of the obtained data into a short molecular pathway revealed a drug treatment-sensitive signaling axis in HCC cells. In conclusion, the results of the present study provide novel drug sensitivity-associated molecular targets for the development of novel personalized and targeted molecular therapies against HCC.