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1.
Infect Drug Resist ; 17: 1669-1673, 2024.
Article in English | MEDLINE | ID: mdl-38707986

ABSTRACT

Lemierre syndrome (LS) is a rare and life-threatening condition predominantly caused by Fusobacterium necrophorum. Currently, there are no standardized clinical guidelines for LS management. Here, we describe the case of a 40-year-old male with fever, productive cough, and dyspnea but no sore throat. Diagnostic radiological examinations revealed multiple pulmonary cavitary nodules and an internal jugular vein occlusion. Metagenomic Next-Generation Sequencing (mNGS) of the alveolar lavage fluid identified Fusobacterium necrophorum, thereby confirming the diagnosis of LS. Intriguingly, the patient exhibited a delayed clinical response despite receiving the appropriate antibiotic. After integrating tigecycline into the treatment to address potential co-infecting bacteria, we observed a marked improvement in his clinical symptoms. Subsequent follow-up over 12 weeks post-discharge revealed complete alleviation of symptoms, and a chest CT scan showed marked regression of the lung lesions.

2.
Article in English | MEDLINE | ID: mdl-38809030

ABSTRACT

OBJECTIVE: This study evaluates the feasibility and efficacy of implanting a leadless pacemaker at the right atrial appendage (RAA) in a preclinical minipig model, aiming to address the limitations of atrial pacing with current leadless devices like the Medtronic Micra, which is typically used for right ventricular implantation. METHODS: Four minipigs, each with a median body weight of 45.8 ± 10.0 kg, underwent placement of the Micra transcatheter pacing system (TPS) via the right femoral vein into the RAA apex. The pacing performance was assessed over 1-week (short-term) and 3-month (long-term) periods. OUTCOMES: The initial findings indicated successful implantation, with satisfactory intrinsic R-wave amplitudes and pacing threshold. In the following period, the sensitivity, threshold, and impedance were stable with time. Notably, upon explanation at 3 months, a deep myocardial penetration by the device was observed, necessitating a redesign for safe long-term use in a growing subject's heart. CONCLUSION: While initial results suggest that RAA apex placement of the Micra TPS is promising for potential inclusion in a dual-chamber pacing system, the issue of myocardial penetration highlights the need for device redesign to ensure safety and effectiveness in long-term applications.

3.
J Colloid Interface Sci ; 670: 576-584, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38776692

ABSTRACT

The misfolding and aggregation of α-synuclein monomers usually cause the occurrence and development of Parkinson's disease (PD). It is important to develop effective methods for detection of α-synuclein aggregates. Carbon dots (CDs) could be the potential fluorescence probe for this purpose owing to their appreciated optical properties. However, undefined structure of CDs and complicated three-dimensional structure of protein severely hindered the design of fluorescence probe towards protein aggregates. Herein, a red emissive fluorescent amphiphilic CD, named as CL-9, was designed with a high sensitivity to α-synuclein fibrils by a one-step heating process, using the ternary carbon source, including Congo red, l-tryptophan and urea. The CL-9 exhibited turn-on red emissive fluorescence towards α-synuclein fibril, but remained no change towards its monomer. Compared with the original Congo red dye, CL-9 exhibited stronger turn-on red fluorescence towards α-synuclein fibrils with better anti-photobleaching resistance, biocompatibility and signal-to-noise ratio. The CL-9 was successful as a fluorescent probe to image α-synuclein fibrils in NL-5901 C. elegans. The present study provided a feasible approach using the multiple carbon sources to construct the CDs based fluorescence probe targeting amyloid proteins.

4.
Obes Rev ; : e13760, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38697953

ABSTRACT

A systematic review and meta-analysis was conducted to evaluate the relative effectiveness of different dietary macronutrient patterns on changes in resting energy expenditure (REE) in relation to weight loss, categorized as minimal (<5%) and moderate to high (>5%). Changes in REE were assessed using a DerSimonian and Laird random-effects meta-analysis. A diet lower in carbohydrates (CHO) or higher in fat and protein was associated with smaller reductions in REE, with these trends being more pronounced among participants who experienced moderate to high weight loss. Adjusted meta-regression analysis indicated that, within the participants who experienced moderate to high weight loss, each 1% increase in CHO intake was associated with a reduction of 2.30 kcal/day in REE (95% CI: -4.11 to -0.47, p = 0.013). In contrast, a 1% increase in protein and fat intake was correlated with an increase in REE by 3.00 (95% confidence interval [CI] [1.02, 5.07], p = 0.003) and 0.5 (95% CI [-2.43, 3.41], p = 0.740) kcal/day, respectively. No significant associations were found among participants who experienced minimal weight loss. These findings indicate that, under a caloric deficit, the impact of dietary macronutrient composition on REE may vary depending on the degree of weight loss and individual metabolic responses.

5.
Telemed Rep ; 5(1): 67-77, 2024.
Article in English | MEDLINE | ID: mdl-38558955

ABSTRACT

Aims: We compared the efficacy, fidelity, acceptability, and feasibility of a creative movement (CM) intervention for children with autism spectrum disorder (ASD), delivered face-to-face (F2F) or through telehealth (TH). Methods: Fifteen children with ASD received the CM intervention F2F or through TH. Motor assessments were used to evaluate effects of F2F and TH interventions on children's motor skills, while video coding was used to assess affect, socially directed verbalization, interpersonal synchrony, and motor coordination during training. Stakeholder feedback and training fidelity data on the intervention were also collected. Results: Children in both subgroups showed similar baseline performance and training-related improvements in motor skills, positive/interested affect, socially directed verbalization, interpersonal synchrony, and dual/multilimb coordination. Parents in the TH subgroup considered the intervention feasible and acceptable; however, they reported greater effort to supervise and redirect their child's attention compared to the F2F subgroup. Trainers for the TH subgroup reported more communication difficulties, technological issues, and longer session lengths, but found greater parental involvement compared to the F2F subgroup. Conclusions: CM interventions are consistent, acceptable, feasible, and effective in improving social, behavioral-affective, and motor skills of children with ASD, regardless of the method of delivery. Clinicians should make efforts to reduce communication/technological issues and parental burden when delivering CM interventions through TH. ClinicalTrials.Gov Study ID-NCT04258254.

6.
J Hematol ; 13(1-2): 46-51, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38644986

ABSTRACT

Extranodal natural killer/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (ENKTCL-LAHS) is a rare disease with poor prognosis. Currently, there are no well-established treatments for LAHS. Almost 50% of patients experience relapsed or refractory disease to anti-hemophagocytic lymphohistiocytosis (HLH) treatment, and the regimen for salvage therapy is limited. We report a case of ENKTCL-LAHS that was successfully treated with a programmed cell death ligand 1 (PD-L1) antibody (sugemalimab) alone and provide a literature review on existing ENKTCL-LAHS treatment options. A 31-year-old man with relapsed ENKTCL complicated by HLH was admitted to our hospital. Following the administration of the PD-L1 antibody sugemalimab, fever was resolved, Epstein-Barr virus (EBV) DNA copy number was negative, and HLH-related blood biochemical markers were decreased in the patient. Consequently, the patient achieved complete remission with a progression-free time (PFS) of 44 months. The prognosis of ENKTCL-LAHS is extremely poor, and the clinical treatment of ENKTCL-HLH is challenging. No previous reports exist regarding the use of PD-L1 antibodies in ENKTCL-LAHS treatment. This study is the first to report a patient with ENKTCL-LAHS treated with the PD-L1 antibody alone, who achieved a long PFS of 44 months. Our results suggest the effectiveness and safety of sugemalimab in the treatment of ENKTCL-LAHS; however, more clinical cases are required for validation. The PD-L1 antibody presents a novel treatment option for patients with ENKTCL-LAHS and warrants further clinical promotion.

7.
Int J Nurs Stud ; 154: 104765, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38642473

ABSTRACT

BACKGROUND: Haemorrhoids are a common chronic anorectal disease, and haemorrhoidectomy is the standard treatment for advanced (grade III and IV) haemorrhoids. Warm water sitz has commonly been used to stimulate urination, cleanse wounds, and decrease pain. Although urinary retention and pain usually occur within the first 24 h after surgery, the warm water sitz bath is provided 24 h after haemorrhoidectomy, which might be a missed opportunity to optimize the quality and efficiency of the care provided. OBJECTIVE: To investigate the effect of early warm water sitz bath on the day of haemorrhoidectomy surgery on preventing urinary retention and reducing wound pain. DESIGN: This was a longitudinal double-blind study with a permuted block randomization design. SETTING(S): This study was conducted in a surgical ward of a medical center. An average of 18 patients receiving hemorrhoid surgery in that ward every month. PARTICIPANTS: A total of 64 participants (32 each in the experimental and control groups) were enrolled. (The first recruitment date is January 16, 2020.) METHODS: Patients who received haemorrhoidectomy for grade III or IV haemorrhoids from January to December 2020 were enrolled. The experimental and control groups received the same conventional treatment and care before the haemorrhoidectomy. The experimental group started warm-water sitz bath 6 h after the surgery, and the control group started warm water sitz bath on post-haemorrhoidectomy day 1 as usual. Urinary retention was defined as use of Foley catheter during the hospital stay or remaining urine volume ≧ 300 ml using the bladder scan. A numerical rating scale was used to rate the pain level. Each participant was evaluated 6 times in total until hospital discharge. The data were analysed by descriptive statistics, chi-square test, and independent samples t test. Generalized estimating equations and intention to treat were used to identify changes in urinary retention and pain over time and missing data, respectively. RESULTS: There was no significant difference in the degree of change in the number of people with urinary retention between groups. A change in the wound pain index was noted; the study group had a statistically significant lower pain score than the control group (B = -0.81, 95 % CI: -1.44 to -0.18). CONCLUSIONS: Early warm water sitz bath was a safe and effective strategy to decrease post-haemorrhoidectomy pain, but not urinary retention. Nurses could provide early warm water sitz bath for post-haemorrhoidectomy patients' comfort. REGISTRATION: ClinicalTrials.gov ID: NCT04535765.

8.
Ecotoxicol Environ Saf ; 273: 116161, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38430581

ABSTRACT

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP is easily leached out to the environment due to the lack of covalent bonds with plastic. High dose of DEHP exposure is often observed in hemodialysis patients because of the continual usage of plastic medical devices. Although the liver is the major organ that catabolizes DEHP, the impact of long-term DEHP exposure on the sensitivity of liver cancer to chemotherapy remains unclear. In this study, we established long-term DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models to investigate the effects and the underlying mechanisms of long-term DEHP exposure on chemosensitivity of HCC. The results showed long-term DEHP exposure potentially increased epithelial-mesenchymal transition (EMT) in HCC cells. Next generation sequencing showed that long-term DEHP exposure increased cell adhesion/migratory related genes expression and blunted sorafenib treatment induced genes alterations. Long-term exposure to DEHP reduced the sensitivity of HCC cells to sorafenib-induced anti-migratory effect by enhancing the EMT transcription factors (slug, twist, and ZEB1) and mesenchymal protein (vimentin) expression. In NOD/SCID mice model, we showed that long-term DEHP-exposed HCC cells exhibited higher growth rate. Regarding the anti-HCC effects of sorafenib, subcutaneous HuH7 tumor grew slowly in sorafenib-treated mice. Nonetheless, the anti-tumor growth effect of sorafenib was not observed in long-term DEHP-exposed mice. Higher mesenchymal markers and proliferating cell nuclear antigen (PCNA) expression were found in sorafenib-treated long-term DEHP-exposed mice. In conclusion, long-term DEHP exposure promoted migratory activity in HCC cells and decreased sorafenib sensitivity in tumor-bearing mice.


Subject(s)
Carcinoma, Hepatocellular , Diethylhexyl Phthalate , Liver Neoplasms , Phthalic Acids , Humans , Mice , Animals , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Sorafenib/pharmacology , Sorafenib/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Diethylhexyl Phthalate/toxicity , Mice, SCID , Mice, Inbred NOD , Treatment Outcome
9.
Res Sq ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38496641

ABSTRACT

Autism Spectrum Disorder (ASD) is among the most prevalent neurodevelopmental disorders, yet the current diagnostic procedures rely on behavioral analyses and interviews and lack objective screening methods. This study seeks to address this gap by integrating upper limb kinematics and deep learning methods to identify potential biomarkers that could be validated in younger age groups in the future to enhance the identification of ASD. Forty-one school-age children, with and without an ASD diagnosis (Mean age ± SE = 10.3 ± 0.4; 12 Females), participated in the study. A single Inertial Measurement Unit (IMU) was affixed to the child's wrist as they engaged in a continuous reaching and placing task. Deep learning techniques were employed to classify children with and without ASD. Our findings suggest delays in motor planning and control in school-age children compared to healthy adults. Compared to TD children, children with ASD exhibited poor motor planning and control as seen by greater number of movement units, more movement overshooting, and prolonged time to peak velocity/acceleration. Compensatory movement strategies such as greater velocity and acceleration were also seen in the ASD group. More importantly, using Multilayer Perceptron (MLP) model, we demonstrated an accuracy of ~ 78.1% in classifying children with and without ASD. These findings underscore the potential use of studying upper limb movement kinematics during goal-directed arm movements and deep learning methods as valuable tools for classifying and, consequently, aiding in the diagnosis and early identification of ASD upon further validation in younger children.

11.
J Am Heart Assoc ; 13(4): e032386, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38348809

ABSTRACT

BACKGROUND: Metabolic disorder is noted for pacing-induced cardiomyopathy. The benefits of His bundle pacing over right ventricular (RV) pacing in preventing pacing-induced cardiomyopathy from a metabolic perspective are yet to be fully understood. METHOD AND RESULTS: Three pig groups were established for this study: sham control, RV pacing (RV pacing for 6 months), and His pacing (RV pacing for 6 months, followed by His bundle pacing for 3 months). Complete atrioventricular block was created in the last 2 groups. Left ventricular function and dyssynchrony were assessed via echocardiography, while proteins linked to metabolism, endoplasmic reticulum stress, and inflammation in left ventricular myocardium were examined. The RV pacing group had significantly more left ventricular mechanical dyssynchrony compared with the other groups. The RV pacing group exhibited triglyceride and diacylglycerol accumulation in cardiomyocytes and higher expression of binding immunoglobulin protein and tumor necrosis factor-α than the other groups. Additionally, the expression of CD36 was activated, while the expression of hormone-sensitive lipase was downregulated in the RV pacing group compared with the His pacing and sham control groups. Furthermore, the expressions of GLUT4 and pyruvate dehydrogenase were higher in the RV pacing group than the sham control and His pacing groups. Notably, the abnormal fatty acid and glucose metabolic pathways in the left ventricular myocardium during RV pacing could be corrected by His bundle pacing. CONCLUSIONS: His bundle pacing can mitigate the abnormal metabolism disorders, endoplasmic reticulum stress, and inflammation induced during RV pacing and may contribute to the superiority of conduction system pacing over RV pacing in reducing heart failure hospitalization.


Subject(s)
Bundle of His , Cardiomyopathies , Animals , Swine , Myocardium , Heart Ventricles , Glucose , Inflammation , Cardiac Pacing, Artificial/methods , Electrocardiography
12.
Mol Ther Methods Clin Dev ; 32(1): 101169, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38187094

ABSTRACT

DNA vaccines for infectious diseases and cancer have been explored for years. To date, only one DNA vaccine (ZyCoV-D) has been authorized for emergency use in India. DNA vaccines are inexpensive and long-term thermostable, however, limited by the low efficiency of intracellular delivery. The recent success of mRNA/lipid nanoparticle (LNP) technology in the coronavirus disease 2019 (COVID-19) pandemic has opened a new application for nucleic acid-based vaccines. Here, we report that plasmid encoding a trimeric spike protein with LNP delivery (pTS/LNP), similar to those in Moderna's COVID-19 vaccine, induced more effective humoral responses than naked pTS or pTS delivered via electroporation. Compared with TSmRNA/LNP, pTS/LNP immunization induced a comparable level of neutralizing antibody titers and significant T helper 1-biased immunity in mice; it also prolonged the maintenance of higher antigen-specific IgG and neutralizing antibody titers in hamsters. Importantly, pTS/LNP immunization exhibits enhanced cross-neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and protects hamsters from the challenge of SARS-CoV-2 (Wuhan strain and the Omicron BA.1 variant). This study indicates that pDNA/LNPs as a promising platform could be a next-generation vaccine technology.

13.
ChemSusChem ; 17(10): e202301508, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38280139

ABSTRACT

Hole mobility is critical to the power conversion efficiencies of perovskite solar cells (PSCs). Organic small-molecule hole-transporting materials (HTMs) have attracted considerable interest in PSCs due to their structural flexibility and operational durability, but they suffer from modest hole mobility. On the other hand, inorganic HTMs with good hole mobility are inflexible in structural variation and exhibit unsatisfactory cell efficiency. In this study, a ligand BT28 and its zinc-based coordination complex BTZ30 were synthesized, characterized, and investigated as HTMs for PSC applications. The mixed-halide perovskites can be grown uniformly with large crystalline grains on both HTMs, which exhibit similar optical and electrochemical properties. However, it was discovered that the BTZ30-based solar cell exhibited an open-circuit voltage of 1.0817 V and a high short-circuit current density of 23.1392 mA cm-2 with a champion power conversion efficiency of close to 20 %. The performance difference between the two HTMs can be attributed to the difference in their hole mobilities, which is 63.31 % higher for BTZ30 than BT28. The comparison of non-metal and metal HTMs revealed the importance of considering hybrid structures to overcome some shortcomings associated with organic and inorganic HTMs and achieve high-performance PSCs.

14.
J Nutr Biochem ; 125: 109565, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38176621

ABSTRACT

Various endogenous and exogenous stimuli can result in an inflammatory response and collagen deposition in the liver, which affect liver function and increase the risk of developing liver cirrhosis and cancer. Rice bran, the main by-product of rice milling, contains various nutrients which possess hepatoprotective activities. In this study, we investigated the effects of rice bran on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Mice were fed a rice-bran-containing diet (10% rice bran w/w) or a standard diet with or without an injection of 20% CCl4 to induce liver fibrosis. Our results showed that feeding a rice-bran-containing diet could alleviate CCl4-induced liver damage, collagen deposition, and expressions of fibrosis-related genes, including α-smooth muscle actin (α-SMA), collagen 1a2 (COL1A2), and transforming growth factor-ß (TGF-ß) in liver tissues. Moreover, consumption of rice bran enhanced phase II detoxification and antioxidant gene expressions, including Gsta3, Gstp1, Catalase, SOD1, SOD2, and SOD3. Treatment with γ-oryzanol, the major bioactive compound in rice bran, decreased the sensitivity of hepatic stellate cells (HSCs) to TGF-ß1-induced α-SMA, COL1A2, and phosphorylated smad2 expressions. In conclusion, a rice-bran-containing diet may have beneficial effects on liver fibrogenesis through increased antioxidant and detoxification activities. γ-Oryzanol, the major bioactive compound of rice bran, can inhibit activation of HSCs.


Subject(s)
Antioxidants , Oryza , Phenylpropionates , Animals , Mice , Antioxidants/metabolism , Oryza/metabolism , Hepatic Stellate Cells/metabolism , Signal Transduction , Liver Cirrhosis/metabolism , Liver/metabolism , Transforming Growth Factor beta1/metabolism , Collagen Type I/genetics , Collagen Type I/metabolism , Diet , Carbon Tetrachloride/toxicity
15.
Life Sci ; 336: 122327, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38061536

ABSTRACT

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, often accompanied by obesity, diabetes, and increased risks of depression and anxiety. Currently, there are no FDA-approved drugs to treat NAFLD and its related systemic symptoms. Previously, we identified a new barbituric acid derivative (BA-5) that expressed effectiveness against fibrosis and drug-resistant hepatocellular carcinoma. AIMS: This study investigated the potential of BA-5 against high-fat diet (HFD)-induced NAFLD and mood disorders in mice. MAIN METHODS: Six-weeks-old male C57BL/6 mice were fed with a 45 % HFD for 8 weeks to induce NAFLD and associated metabolic disorders. Mice were treated with a BA-5 and the therapeutic effects and the underlying molecular mechanisms were investigated. KEY FINDINGS: Administration of BA-5 significantly reduced serum levels of alanine aminotransferase (ALT), low-density lipoprotein (LDL), fatty acids (FA), and triglycerides (TG) in HFD-fed mice. BA-5 treatment decreased expressions of hepatic lipogenesis-related markers (acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and ATP-citrate lyase (ACLY)), increased fatty acid oxidation markers (carnitine palmitoyltransferase 1A (CPT1A) and acyl-CoA oxidase 1 (ACOX1)), and attenuated hepatic fat accumulation in HFD-fed mice. Moreover, HFD-induced adipocyte size enlargement and activation of lipolysis markers such as phosphorylated (p)-hormone-sensitive lipase (HSL) 565, p-HSL 660, and perilipin were inhibited in BA-5-treated mice. Notably, HFD-induced anxiety- and depression-like behaviors significantly improved in the BA-5 treated group through enhanced anti-inflammatory responses in the hippocampus. SIGNIFICANCE: This study provides new insights into clinical therapeutic strategies of barbituric acid derivatives for HFD-induced NAFLD and associated mood disturbances.


Subject(s)
Non-alcoholic Fatty Liver Disease , Male , Animals , Mice , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Mice, Inbred C57BL , Liver/metabolism , Diet, High-Fat/adverse effects
16.
Biomol Biomed ; 24(2): 360-373, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-37676057

ABSTRACT

The molecular and genetic mechanisms underlying left atrial (LA) enlargement and atrial fibrosis following right ventricular (RV) dependent pacing remain unclear. Our objective was to investigate genetic expressions in the LA of pigs subjected to RV pacing for atrioventricular block (AVB), as well as to identify the differential gene expressions affected by biventricular (BiV) pacing. We established an AVB pig model and divided the subjects into three groups: a sham control group, an RV pacing group, and a BiV pacing group. Differential expression genes (DEGs) analyses conducted through next-generation sequencing (NGS) and enrichment analyses were employed to identify genes with altered expression in the LA myocardium. The RV pacing group showed a significant increase in extracellular fibrosis in the LA myocardium compared to the control group. NGS analysis revealed suppressed expression of the sirtuin signaling pathway in the RV pacing group. Among the DEGs within this pathway, GADD45G was found to be downregulated in the RV pacing group and upregulated in the BiV pacing group. Remarkably, the BiV pacing group exhibited elevated levels of GADD45G protein. In our study, we observed significant downregulation of SIRT1 and GADD45G genes, which are associated with the sirtuin signaling pathway, in the LA myocardium of the RV pacing group when compared to the control group. Moreover, these genes, which were downregulated in the RV pacing group, displayed a noteworthy upregulation in the BiV pacing group when compared to the RV pacing group.


Subject(s)
Atrioventricular Block , Cardiac Resynchronization Therapy , Humans , Animals , Swine , Sirtuin 1 , Down-Regulation , Heart Ventricles , GADD45 Proteins
17.
Int J Mol Sci ; 24(23)2023 Nov 23.
Article in English | MEDLINE | ID: mdl-38068962

ABSTRACT

During glycolysis, the muscle isoform of pyruvate kinase PKM2 produces ATP in exchange for dephosphorylation of phosphoenolpyruvate (PEP) into pyruvate. PKM2 has been considered as a tumor-promoting factor in most cancers, whereas the regulatory role of PKM2 during head and neck carcinogenesis remained to be delineated. PKM2 mRNA and protein expression was examined in head and neck tumorous specimens. The role of PKM2 in controlling cellular malignancy was determined in shRNA-mediated PKM2-deficient head and neck squamous cell carcinoma (HNSC) cells. In agreement with the results in other cancers, PKM2 expression is enriched in both mouse and human HNSC tissues. Nevertheless, PKM2 mRNA expression reversely correlated with tumor stage, and greater recurrence-free survival rates are evident in the PKM2high HNSC population, arguing that PKM2 may be tumor-suppressive. Multifaceted analyses showed a greater in vivo xenografic tumor growth and an enhanced cisplatin resistance in response to PKM2 loss, whereas PKM2 silencing led to reduced cell motility. At the molecular level, metabolic shifts towards mitochondrial metabolism and activation of oncogenic Protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK) signals were detected in PKM2-silencing HNSC cells. In sum, our findings demonstrated that PKM2 differentially modulated head and neck tumorigenicity via metabolic reprogramming.


Subject(s)
Head and Neck Neoplasms , Pyruvate Kinase , Animals , Humans , Mice , Carcinogenesis/genetics , Cell Line, Tumor , Cisplatin , Glycolysis/genetics , Head and Neck Neoplasms/genetics , Pyruvate Kinase/genetics , Pyruvate Kinase/metabolism , RNA, Messenger/metabolism , Squamous Cell Carcinoma of Head and Neck/genetics
18.
Int J Mol Sci ; 24(23)2023 Nov 23.
Article in English | MEDLINE | ID: mdl-38068984

ABSTRACT

Despite recent advancements, therapies against advanced oral squamous cell carcinoma (OSCC) remain ineffective, resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Although the effects of CAP in abrogating OSCC have been explored, the exact mechanisms driving CAP-induced cancer cell death and the changes in microRNA (miRNA) expression are not fully understood. We fabricated and calibrated an argon-CAP device to explore the effects of CAP irradiation on the growth and expression of oncogenic miRNAs in OSCC. The analysis revealed that, in OSCC cell lines following CAP irradiation, there was a significant reduction in viability; a downregulation of miR-21, miR-31, miR-134, miR-146a, and miR-211 expression; and an inactivation of the v-akt murine thymoma viral oncogene homolog (AKT) and extracellular signal-regulated kinase (ERK) signals. Pretreatment with blockers of apoptosis, autophagy, and ferroptosis synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways via CAP. Combined treatments using death inhibitors and miRNA mimics, alongside the activation of AKT and ERK following the exogenous expression, counteracted the cell mortality associated with CAP. The CAP-induced downregulation of miR-21, miR-31, miR-187, and miR-211 expression was rescued through survival signaling. Additionally, CAP irradiation notably inhibited the growth of SAS OSCC cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study provides new lines of evidence demonstrating that CAP irradiation diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , MicroRNAs , Mouth Neoplasms , Humans , Animals , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Mouth Neoplasms/genetics , Mouth Neoplasms/radiotherapy , Mouth Neoplasms/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Mice, Nude , Squamous Cell Carcinoma of Head and Neck/genetics , Head and Neck Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic
19.
Am J Occup Ther ; 77(6)2023 Nov 01.
Article in English | MEDLINE | ID: mdl-38048263

ABSTRACT

IMPORTANCE: The efficacy of telehealth (TH) interventions needs to be studied. OBJECTIVE: To compare the efficacy, fidelity, acceptability, and feasibility of face-to-face (F2F) versus TH seated play (SP) interventions among children with autism spectrum disorder (ASD). DESIGN: As part of a larger randomized controlled trial, children were assigned to the SP group and received TH and F2F interventions over 8 wk using a pretest-posttest study design. SETTING: A research lab or through videoconferencing. PARTICIPANTS: Fifteen children with ASD (ages 5-14 yr) were randomly assigned to the SP group and received the intervention F2F or through TH. INTERVENTION: Children received 16 SP intervention sessions (2 sessions per week for 8 wk). OUTCOMES AND MEASURES: Pretests and posttests included standardized fine motor assessments. Video coding compared socially directed verbalization during training sessions. Parents and trainers provided feedback on their experiences. RESULTS: Seven children received the intervention F2F, whereas 8 received TH intervention. Children in both subgroups showed similar training improvements in fine motor skills and socially directed verbalizations (ps > .01). Parents rated both interventions as acceptable and feasible; however, they reported longer preparation time and effort during TH interventions (ps < .01). Trainers reported greater parental involvement but more communication and technological issues during TH interventions. Fidelity checks indicated fewer reinforcements during TH versus F2F sessions. CONCLUSIONS AND RELEVANCE: TH intervention is feasible and effective in improving fine motor and social communication performance. Clinicians should reduce parental burden and overcome technological issues. What This Article Adds: This study confirmed the efficacy, fidelity, acceptability, and feasibility of delivering seated play, standard of care interventions for children with autism spectrum disorder via telehealth. However, clinicians should work on reducing parental burden and overcoming communication and technological issues related to telehealth.


Subject(s)
Autism Spectrum Disorder , Telemedicine , Child , Humans , Autism Spectrum Disorder/therapy , Communication , Feasibility Studies , Parents/education , Child, Preschool , Adolescent
20.
JAMA Netw Open ; 6(12): e2350367, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38150258

ABSTRACT

This cross-sectional study analyzes the accuracy of nutrition information from artificial intelligence (AI) in comparison with a nutritionist.


Subject(s)
Artificial Intelligence , Nutritional Sciences , Nutritional Sciences/standards
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