Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.

HER2+ breast tumors have abundant immune-suppressive cells, including M2-type tumor-associated macrophages (TAMs). Although TAMs consist of the immune-stimulatory M1 type and immune-suppressive M2 type, the M1/M2-TAM ratio is reduced in immune-suppressive tumors, contributing to their immunotherapy refractoriness. M1- versus M2-TAM formation depends on differential arginine metabolism, where M1-TAMs convert arginine to nitric oxide (NO) and M2-TAMs convert arginine to polyamines (PAs). We hypothesize that such distinct arginine metabolism in M1- versus M2-TAMs is attributed to different availability of BH4 (NO synthase cofactor) and that its replenishment would reprogram M2-TAMs to M1-TAMs. Recently, we reported that sepiapterin (SEP), the endogenous BH4 precursor, elevates the expression of M1-TAM markers within HER2+ tumors. Here, we show that SEP restores BH4 levels in M2-like macrophages, which then redirects arginine metabolism to NO synthesis and converts M2 type to M1 type. The reprogrammed macrophages exhibit full-fledged capabilities of antigen presentation and induction of effector T cells to trigger immunogenic cell death of HER2+ cancer cells. This study substantiates the utility of SEP in the metabolic shift of the HER2+ breast tumor microenvironment as a novel immunotherapeutic strategy.

Decoding LncRNA in COPD: Unveiling Prognostic and Diagnostic Power and Their Driving Role in Lung Cancer Progression.

Chronic obstructive pulmonary disease (COPD) and lung cancer represent formidable challenges in global health, characterized by intricate pathophysiological mechanisms and multifaceted disease progression. This comprehensive review integrates insights from diverse perspectives to elucidate the intricate roles of long non-coding RNAs (lncRNAs) in the pathogenesis of COPD and lung cancer, focusing on their diagnostic, prognostic, and therapeutic implications. In the context of COPD, dysregulated lncRNAs, such as NEAT1, TUG1, MALAT1, HOTAIR, and GAS5, emerge as pivotal regulators of genes involved in the disease pathogenesis and progression. Their identification, profiling, and correlation with the disease severity present promising avenues for prognostic and diagnostic applications, thereby shaping personalized disease interventions. These lncRNAs are also implicated in lung cancer, underscoring their multifaceted roles and therapeutic potential across both diseases. In the domain of lung cancer, lncRNAs play intricate modulatory roles in disease progression, offering avenues for innovative therapeutic approaches and prognostic indicators. LncRNA-mediated immune responses have been shown to drive lung cancer progression by modulating the tumor microenvironment, influencing immune cell infiltration, and altering cytokine production. Their dysregulation significantly contributes to tumor growth, metastasis, and chemo-resistance, thereby emphasizing their significance as therapeutic targets and prognostic markers. This review summarizes the transformative potential of lncRNA-based diagnostics and therapeutics for COPD and lung cancer, offering valuable insights into future research directions for clinical translation and therapeutic development.

The Effect of Oral Diet Training in Indwelling Nasogastric Tube Patients with Prolonged Dysphagia.

Background: Patients with severe dysphagia are usually fed using a nasogastric tube (NGT). Many patients who receive long-term NGT feeding are unable to obtain sufficient nutrients orally immediately after NGT removal. Thus, a transitional period involving oral diet training is required to transition from NGT feeding to exclusive oral feeding. We aimed to investigate the therapeutic effect of oral diet training in indwelling NGT patients with prolonged dysphagia. Methods: A total of 175 patients who were fed using an NGT for more than 4 weeks were enrolled. Their swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS). During the VFSS, patients received thick and thin barium while the NGT was inserted. Then, the patients underwent a VFSS without an NGT thirty minutes after NGT removal. If a patient had no aspiration with NGT inserted during the VFSS, oral diet training combined with NGT feeding was recommended. Results: Of the 49 indwelling NGT patients who were recommended to receive oral diet training, 39 (79.6%) transitioned to exclusive oral feeding. A transition period of 2-8 weeks was required for them to achieve full oral feeding. Patients who were eligible for oral feeding trials showed no significant aspiration during the VFSS with an NGT inserted and had sufficient cough function. Patients who required prolonged NGT feeding and who could not complete oral trials showed significant aspiration during the VFSS when an NGT was inserted. Conclusions: This study demonstrated that oral diet training combined with NGT feeding is safe in patients with prolonged dysphagia who have sufficient cough function and no aspiration during VFSS. We suggest that if the patient is a proper candidate for NGT removal, direct oral feeding training with an NGT inserted could be a useful therapeutic strategy during the transitional period from long-term NGT feeding to successful oral feeding.

Cervical ganglioneuroma as a rare cause of cervicogenic headache: A case report and literature review.

BACKGROUND: Cervicogenic headache is characterized by chronic posterior neck pain radiating to one side of the head, resulting from cervical spine bone or soft tissue diseases. Cervical ganglioneuroma (GN), a rare benign neuroblastic tumor, especially in the cervical spine, may cause cervicogenic headache-like symptoms. OBJECTIVE: We report a case of GN which was surgically removed successfully to relieve the symptom. CASE REPORT: A 68-year-old male presented with right posterior neck pain with referred pain to the ipsilateral occipital area in May 2020. Despite administration of medications, physical therapy, and spine interventions, the symptoms intermittently recurred over one year. In July 2021, the patient complained of painful limitation of neck motion, especially on right-sided bending; no motor or sensory deficits, except for subjective numbness of the finger tips, were detected. Plain radiography of the cervical spine showed moderate degenerative changes in the mid-cervical spine. Cervical MRI revealed a cystic mass (1.5 cm × 0.5 cm × 1 cm-in size) around the right C2 dorsal root ganglion adjacent to the C1-C2 facet joint. His symptoms significantly improved after complete tumor excision. CONCLUSION: GN of the upper cervical spine should be considered when persistent cervicogenic headache is refractory to conservative management. In such a case, advanced imaging studies such as MRI should be performed for early diagnosis and appropriate treatment.

Advances in Aß imaging probes: a comprehensive study of radiolabelled 1,3-diaryl-2-propen-1-ones for Alzheimer's disease: a review.

Alzheimer's disease (AD) is a formidable neurodegenerative disorder characterized by cognitive decline, memory impairment and inability to perform everyday tasks. In the pursuit of innovative diagnostic and therapeutic strategies, the synthesis and application of radiolabelled compounds have garnered significant attention. This review delves into the synthesis and biological significance of radiolabelled 1,3-diaryl-2-propen-1-ones, commonly known as chalcones, as Aß imaging probes for AD. These versatile chalcone derivatives have demonstrated noteworthy potential as radiotracers for visualizing Aß imaging probes, which are hallmark pathologies of AD. This review encompasses an exploration of chalcone synthesis via diverse methodologies and their biological implications, both as standalone entities and as precursors for intricate natural products. In addition, the pivotal role of advanced imaging techniques, such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET), using various radioisotopes is highlighted. The use of radiopharmaceutical agents, including [18F]FDG, [18F]FMAPO, [11C]6-Me-BTA-1, [124/125I]IBETA, and [64Cu]YW-7 as potent tools for early diagnosis and therapeutic advancement is explored. This review underscores the critical nexus between radiolabelled chalcones and their pivotal role in advancing diagnostic and therapeutic paradigms in AD research. Furthermore, this study encapsulated the role of radiolabelled chalcone emphasizing their prospective implications for drug development and therapeutic interventions. A focal point of paramount significance is the elucidation of Aß imaging probes and its important role in the combat against AD, with a particular emphasis on their role in facilitating early diagnosis and fostering advancements in therapeutic strategies.

How long does it to achieve sagittal realignment of the displaced epiphysis in Salter-Harris type II distal radial fracture when treated by manual reduction?

This study aimed to investigate how long it takes for the dorsally displaced distal radial epiphysis to achieve realignment. We retrospectively reviewed 56 patients with dorsally displaced Salter-Harris type II distal radial epiphyseal fractures who were aged ≤15 years at the time of injury. All fractures were treated with closed reduction and immobilised using a sugar tong splint for 6 weeks. We evaluated the change in the displaced epiphysis position (%) until 12 weeks and the long-term clinical and radiological outcomes. We analysed significant differences in demographic factors and epiphyseal displacement according to the required period for epiphyseal realignment. The estimated area of the receiver operating characteristics (ROC) curve was calculated, and cut-off values were suggested to predict the required period for epiphyseal realignment. Sixteen (28.6%) and 42 (75%) patients achieved realignment of the epiphysis within 8 and 12 weeks, respectively. The cut-off values of 13.1 and 22.9% displacement at the 1-week follow-up were the best predictors of epiphyseal realignment within 8 and 12 weeks, respectively. Patients with a residual displacement of up to 51.3% in the sagittal plane at the 1-week follow-up achieved complete realignment of the epiphysis at the 6-month follow-up. From this study, we could predict the timing of epiphyseal realignment, and expect epiphyseal realignment even if re-displacement occurred up to 51.3% at the 1-week follow-up.

The effect of extracorporeal shock wave therapy on large neurogenic heterotopic ossification in a patient with pontine hemorrhage: A case report and literature review.

RATIONALE: Heterotopic ossification (HO), an ectopic bone formation in soft tissue around the joint, is a complication observed in stroke patients. HO around the hip joint causes a reduction in the functional ability of patients by generating pain and limiting range of motion (ROM). In addition, it results in impaired mobility, ultimately affecting quality of life and increasing the mortality of patients. Extracorporeal shock wave therapy (ESWT) has demonstrated efficacy in treating soft tissue inflammation and has been used to reduce patients' pain in HO. However, almost none of the studies reported degradation in the size of HO on images obtained before and after ESWT application. PATIENT CONCERNS AND DIAGNOSIS: We report a case of a 36-year-old man who developed HO around both hip joints 3 months after bilateral pontine hemorrhage. INTERVENTIONS: Seven months after HO development, ESWT was administered to the area of HO every other day for a total of 10 sessions. OUTCOMES: Immediately following treatment, the ROM of both hip joints increased. Thus the patient was able to maintain a sitting posture without having to be bound to the wheelchair. In addition, the tolerable sitting time before groaning increased from less than ten minutes to almost 60 minutes by the end of all ESWT sessions. Unlike other previous reports, a diminished HO size was confirmed by comparing plain X-rays and bone scans obtained before and after treatment sessions. LESSONS: In this case, we report an objective size reduction in HO in radiologic findings after applying ESWT to both hips. ESWT is a safe, easy-to-apply, and noninvasive modality. We would like to emphasize the use of ESWT as a treatment option for HO to decrease the extent of HO, as well as to improve pain, spasticity and function in patients with stroke.

Nerve root anomaly as a cause of unexpected outcomes of epidural steroid injections in lumbar radiculopathy: A case report.

BACKGROUND: Spinal nerve root anomaly is a rare feature that can result in unexpected outcomes in epidural steroid injections or surgical procedures. Preoperative diagnostic tools for root anomalies are limited, as they are usually found intraoperatively. OBJECTIVE: This case report aims to propose an effective diagnostic process for nerve root anomalies by introducing clinical manifestations, electrodiagnostic findings, and sophisticated imaging techniques such as coronal view magnetic resonance imaging (MRI) of the lumbosacral spine. CASE DESCRIPTION: A 43-year-old female complained of low back pain with radicular pain to the lower extremities. Based on physical examination, electrodiagnosis, and imaging studies, right L5 radiculopathy was diagnosed. Repetitive image-guided epidural steroid injections presented unsuccessful outcomes. She was then referred to a neurosurgeon for surgical decompression, which resulted in significant improvement in her radicular pain. A nerve root anomaly was found intraoperatively, and the coronal images of postoperative MRI depicted the conjoined nerve root of the lumbar spine. CONCLUSION: When proper image-guided spinal interventions for discogenic radicular pain are not effective, a clinician should be advised to consider the possibility of anatomical variation, including nerve root anomalies. Early diagnosis of nerve root anomalies by utilizing multiple diagnostic tools, especially coronal MRI, can aid in preoperative diagnosis and proper clinical decisions for symptom management.

The Effect of Branched Chain Amino Acid Supplementation on Stroke-Related Sarcopenia.

Background: Stroke-related sarcopenia is caused by various factors, such as brain damage, systemic catabolic state, skeletal muscle imbalance, and malnutrition. In the long-term care plan after stroke, appropriate rehabilitation strategies to achieve maximum functional improvement and prevent the development of sarcopenia are important. This study has investigated the effect of branched-chain amino acid (BCAA) supplementation on sarcopenia after stroke. We also evaluated the effect of BCAA on functional improvement during the intensive rehabilitation period. Methods: Patients with subacute stroke with stroke-related disabilities were enrolled and given dietary supplement powder containing BCAAs for 1 month. These BCAAs were supplied through the nutrition team during feeding time. Patients whose age, sex, and stroke lesions were similar to those of the study group were enrolled in the control group through medical record review. Both groups received personalized intensive inpatient rehabilitation therapy in a single-unit rehabilitation center. All patients' target calories were calculated regularly by the nutritional support team in our institution. Sarcopenia status was evaluated using grip strength and the skeletal muscle index (SMI), which was assessed by dual-energy X-ray absorptiometry (DEXA). The functional status associated with stroke was evaluated every month, including activities of daily living, balance, gait, and swallowing. Results: A total of 54 patients were enrolled, with 27 patients in each of the two groups. The study group showed significantly greater improvement in SMI after intervention than the control group. Both groups improved functionally over time, but the improvement in the study group was significantly greater than that in the control group. Univariate analysis revealed that patients with better functional status had a greater SMI with a combination of BCAA supplementation and intensive rehabilitation therapy. Conclusion: Our results showed a positive effect of BCAA supplementation on sarcopenia after stroke. We also found that nutritional support helps functional improvement during neurological recovery. These results suggest that comprehensive rehabilitation intervention combined with BCAA supplementation could be a helpful option during the critical period of post-stroke neurological recovery.

Double Eyelid Tape as a Treatment Option for Severe Ptosis in Patients With Myotonic Dystrophy Type 1.

ABSTRACT: Myotonic dystrophy is a systemic disorder associated with progressive muscle weakness of the limbs and multiorgan dysfunction. This condition commonly affects the levator palpebrae superioris muscle, which leads to ptosis and eventually affects patients' activities of daily living. The effects of ptosis on activities of daily living are usually overlooked; therefore, the importance of treatment is underestimated, and surgical procedures are considered infeasible in patients with preexistent levator palpebrae superioris muscle weakness. This case report describes the case of a middle-aged man with myotonic dystrophy type 1, who presented with ptosis, which significantly restricted his participation in rehabilitation and activities of daily living secondary to a limited visual field. He was evaluated by an ophthalmologist; however, surgery was contraindicated in view of the high risk of complications, such as exposure keratitis and corneal ulcer. Double eyelid tapes were used as a nonsurgical intervention, which significantly increased the palpebral fissure height and improved the visual field, with a higher modified functional index score. Double eyelid tapes may serve as an effective, safe, and reliable therapeutic option for severe ptosis in patients with myotonic dystrophy.

Relationship of Bone Mineral Density and Knee Osteoarthritis (Kellgren-Lawrence Grade): Fifth Korea National Health and Nutrition Examination Survey.

BACKGROUND: Osteoarthritis (OA) and osteoporosis (OP) are the 2 most common bone disorders associated with aging. We can simply assume that older patients have a higher incidence of OA and OP with more severity. Although several papers have conducted studies on the relationship between OA and OP, none of them has demonstrated a conclusive link. In this study, we used radiological knee OA and bone mineral density (BMD; T-score of the total hip and lumbar spine) to analyze the incidence of OA and OP in a large population. We aimed to determine the relationship between OA and OP and investigate the associated risk factors. METHODS: This cross-sectional study used data extracted from the 2010-2012 Korea National Health and Nutrition Examination Survey. We evaluated a total of 4,250 participants aged ≥ 50 years who underwent knee radiography and dual-energy X-ray absorptiometry and their laboratory results. The relationship between radiological knee OA and BMD was assessed. The generalized linear model was used to evaluate the relationship between BMD and Kellgren-Lawrence (KL) grade. RESULTS: The higher KL grade was associated with older age, higher body mass index (BMI), female sex, and lower hemoglobin level (p < 0.001). No significant association was found between OA and the following variables: white blood cell, platelet, total cholesterol, vitamin D, alkaline phosphatase, parathyroid hormone, hypertension, diabetes, asthma, dyslipidemia, smoking status, alcohol consumption, and regular exercise (p > 0.05). After adjusting for confounding factors (age, BMI, diabetes, hypertension, smoking, and alcohol consumption), the average T-scores of total hip and lumbar spine were the highest in the mild OA group with KL grade 2 (-0.22 ± 1.08 and -0.89 ± 1.46, respectively, p < 0.001). The average T-scores of the total hip and lumbar spine significantly decreased as OA progressed from moderate (KL grade 3; -0.49 ± 1.05 and -1.33 ± 1.38, respectively, p < 0.001) to severe (KL grade 4; -0.73 ± 1.13 and -1.74 ± 1.75, respectively, p < 0.001). T-scores of the moderate-to-severe OA group were significantly lower than those of the non-OA group (KL grades 0 and 1, p < 0.001). CONCLUSIONS: Compared with the non-OA group, BMD (T-scores of the total hip and lumbar spine) was higher in the mild OA group and lower in the moderate-to-severe OA group.

Machine-learning algorithm that can improve the diagnostic accuracy of septic arthritis of the knee.

PURPOSE: Prompt diagnosis and treatment of septic arthritis of the knee is crucial. Nevertheless, the quality of evidence for the diagnosis of septic arthritis is low. In this study, the authors developed a machine learning-based diagnostic algorithm for septic arthritis of the native knee using clinical data in an emergency department and validated its diagnostic accuracy. METHODS: Patients (n = 326) who underwent synovial fluid analysis at the emergency department for suspected septic arthritis of the knee were enrolled. Septic arthritis was diagnosed in 164 of the patients (50.3%) using modified Newman criteria. Clinical characteristics of septic and inflammatory arthritis were compared. Area under the receiver-operating characteristic (ROC) curve (AUC) statistics was applied to evaluate the efficacy of each variable for the diagnosis of septic arthritis. The dataset was divided into independent training and test sets (comprising 80% and 20%, respectively, of the data). Supervised machine-learning techniques (random forest and eXtreme Gradient Boosting: XGBoost) were applied to develop a diagnostic model using the training dataset. The test dataset was subsequently used to validate the developed model. The ROC curves of the machine-learning model and each variable were compared. RESULTS: Synovial white blood cell (WBC) count was significantly higher in septic arthritis than in inflammatory arthritis in the multivariate analysis (P = 0.001). In the ROC comparison analysis, synovial WBC count yielded a significantly higher AUC than all other single variables (P = 0.002). The diagnostic model using the XGBoost algorithm yielded a higher AUC (0.831, 95% confidence interval 0.751-0.923) than synovial WBC count (0.740, 95% confidence interval 0.684-0.791; P = 0.033). The developed algorithm was deployed as a free access web-based application ( www.septicknee.com ). CONCLUSION: The diagnosis of septic arthritis of the knee might be improved using a machine learning-based prediction model. LEVEL OF EVIDENCE: Diagnostic study Level III (Case-control study).

Genetically confirmed limb-girdle muscular dystrophy type 2B with DYSF mutation using gene panel sequencing: A case report.

RATIONALE: The limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of disorders characterized by progressive proximal muscle weakness and have more than 30 different subtypes linked to specific gene loci, which manifest as highly overlapping and heterogeneous phenotypes. PATIENT CONCERNS: A 59-year-old male presented for evaluation of progressive muscle weakness since his late twenties. When he was 38 years old, he had muscle weakness in the upper extremities and had a waddling gait, hyper lordosis of lower back, and anterior pelvic tilt. His gait disturbance and muscle weakness slowly progressed. When he was 55 years old, he could not walk at all and had to use a wheelchair for ambulation. DIAGNOSIS: Next-generation sequencing using a custom target capture-based gene panel including specific genes responsible for muscular dystrophy was performed. As a result, the proband was genetically diagnosed as LGMD type 2B, carrying 2 compound heterozygous mutations (NM_003494.3:c.1663C>T, p.Arg555Trp; rs377735262 and NM_003494.3:c.2997G>T, p.Trp999Cys; rs28937581) of the DYSF gene. INTERVENTIONS: Physical and occupational therapy were prescribed properly for the first time Bracing and assistive devices were adapted specifically to the patient's deficiencies to preserve mobility and function and prevent contractures. OUTCOMES: The patient with LGMD has periodic assessments of physical and occupational therapy for the prevention and management of comorbidities. However, in the 3 years after the gene panel sequencing diagnoses, his weakness was slowly progress and the patient still could not walk. LESSONS: Gene panel sequencing allows for the correct recognition of different LGMD subtypes, improving timely treatment, management, and enrolment of molecularly diagnosed individuals in clinical trials.

Coexistence of digenic mutations in the collagen VI genes (COL6A1 and COL6A3) leads to Bethlem myopathy.

INTRODUCTION: Bethlem myopathy is a kind of collagen VI related myopathy which affects proximal skeletal muscles and leads to gait disturbance and multiple joint contractures with an onset in the first two decades of life. Lung function impairment (respiratory muscle and diaphragmatic weakness, ventilatory restriction, hypoxaemia and hypercapnia) and respiratory failure are part of the clinical spectrum and can occur in ambulatory patients. METHODOLOGY: We carried out whole exome sequencing (WES) in combination with neuromuscular diseases-associated genes-filtering to detect the possible causative mutation(s) in a Korean family with Bethlem myopathy. An electrodiagnostic study showed myopathic pattern (normal nerve conduction study, and early recruitment and short amplitude muscle unit action potentials) in the proband. RESULTS: Coexistence of digenic mutations in the collagen VI genes (COL6A1 and COL6A3) was identified by WES in the proband only: heterozygous missense mutations of the COL6A1 (NM_001848.2: c.823G > T, p.Gly275Trp; rs1556425467) and of the COL6A3 genes (NM_004369.3: c.9349G > A, p.Asp3117Asn; rs1226664855). COL6A3 mutation may be candidate as disease-associated variant, as far as it was found only in the proband harboring another heterozygous mutation in COL6A1 gene, previously reported as different pathogenic mutations (p.Gly275Arg and p.Gly275Glu) at the same codon in Bethlem myopathy. CONCLUSION: Our findings suggest that the coexistence of these digenic mutations is rare, but it may be used for the risk evaluation of individuals with a possible susceptibility to Bethlem myopathy. Taken together, genetic diagnosis using WES is a useful approach for the identification of pathogenic mutations associated with Bethlem myopathy.

A novel SYNE2 mutation identified by whole exome sequencing in a Korean family with Emery-Dreifuss muscular dystrophy.

INTRODUCTION: Emery-Dreifuss muscular dystrophy (EDMD) also known as humeroperoneal muscular dystrophy, is a skeletal myopathy characterized by the clinical triad of progressive muscular weakness, joint contractures, and cardiac disease. METHODOLOGY: Herein, we reported a family including two patients (the proband and his son) affected with progressive muscular dystrophy manifested by joint contractures without cardiac involvement ("EDMD-like" phenotype). Interestingly, electodiagnostic study results of the proband showed a neuropathic pattern different from the myopathic pattern in most muscular dystrophy patients. To identify the underlying genetic cause, genomic DNA of the proband was analyzed by WES using Agilent's SureSelect XT Human All Exon v5. RESULTS: A novel de novo pathogenic heterozygous missense mutation (NM_182914.2: c.4858G > A; p.Ala1620Thr) of the SYNE2 gene, which had not been previously reported was identified by whole exome sequencing in the proband and by Sanger sequencing in his son. CONCLUSION: To the best knowledge, SYNE2 mutation was reported first by whole exome sequencing in a Korean family with EDMD-like features. We emphasized the role of genetic analysis using whole exome sequencing, which allows the correct recognition of this molecular diagnosis and brings together the neuromuscular spectrum of this complex clinical scenario, leading to proper clinical management.

Dietary Compounds for Targeting Prostate Cancer.

Prostate cancer is the third most common cancer worldwide, and the burden of the disease is increased. Although several chemotherapies have been used, concerns about the side effects have been raised, and development of alternative therapy is inevitable. The purpose of this study is to prove the efficacy of dietary substances as a source of anti-tumor drugs by identifying their carcinostatic activities in specific pathological mechanisms. According to numerous studies, dietary substances were effective through following five mechanisms; apoptosis, anti-angiogenesis, anti-metastasis, microRNA (miRNA) regulation, and anti-multi-drug-resistance (MDR). About seventy dietary substances showed the anti-prostate cancer activities. Most of the substances induced the apoptosis, especially acting on the mechanism of caspase and poly adenosine diphosphate ribose polymerase (PARP) cleavage. These findings support that dietary compounds have potential to be used as anticancer agents as both food supplements and direct clinical drugs.

The therapeutic effect and complications of oro-esophageal tube training in stroke patients.

Background: Patients with severe dysphagia after stroke are usually fed using a nasogastric tube. However, this method is inconvenient and causes complications. The oro-esophageal (OE) tube has been used as an alternative parenteral feeding method for patients for whom safe oral feeding is impossible. This study aimed to evaluate the therapeutic effects and complications of OE tube feeding in stroke patients with dysphagia. Methods: This study was designed as a retrospective medical chart review of dysphagic stroke patients who were recommended for OE tube feeding. Thirty-eight stroke patients were recommended for OE tube feeding according to videofluoroscopic swallowing study (VFSS) findings. Of those patients, 17 received OE tube feeding training and conventional dysphagia therapy. Follow-up VFSSs were performed sequentially based on the patients' conditions. When a patient was able to swallow therapeutic foods with specific viscosities during the VFSS, oral feeding was considered to be initiated. Patients were divided into two groups according to final feeding methods. Results: Seventeen patients attempted OE tube feeding. Among them, 64.7% of the patients could change to full oral feeding at their follow-up VFSS evaluation. Additionally, 70.6% of the patients showed gastroesophageal reflux disease regardless of whether they changed to oral feeding. On individual items of the Functional Dysphagia Scale, both groups showed significant improvements in the triggering of pharyngeal swallowing, the amount of residue, and the pharyngeal transit time. These functions were better improved in the patients who could change to oral feeding than in those who could not. Both groups showed significant aggravation of nasal penetration. Conclusion: Our study quantitatively shows the therapeutic effects and complications of OE tube training. OE tube feeding can facilitate the swallowing process and assist patients in transitioning to oral feeding. This easy-to-apply technique may significantly impact future treatment strategies in stroke patients with severe dysphagia.

KIN-4/MAST kinase promotes PTEN-mediated longevity of Caenorhabditis elegans via binding through a PDZ domain.

PDZ domain-containing proteins (PDZ proteins) act as scaffolds for protein-protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN-4, a PDZ domain-containing microtubule-associated serine-threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Through a targeted genetic screen for PDZ proteins, we find that kin-4 is required for the long lifespan of daf-2/insulin/IGF-1 receptor mutants. We then show that neurons are crucial tissues for the longevity-promoting role of kin-4. We find that the PDZ domain of KIN-4 binds PTEN, a key factor for the longevity of daf-2 mutants. Moreover, the interaction between KIN-4 and PTEN is essential for the extended lifespan of daf-2 mutants. As many aspects of lifespan regulation in C. elegans are evolutionarily conserved, MAST family kinases may regulate aging and/or age-related diseases in mammals through their interaction with PTEN.

Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C. elegans.

Heat shock factor 1 (HSF-1) and forkhead box O (FOXO) are key transcription factors that protect cells from various stresses. In Caenorhabditis elegans, HSF-1 and FOXO together promote a long life span when insulin/IGF-1 signaling (IIS) is reduced. However, it remains poorly understood how HSF-1 and FOXO cooperate to confer IIS-mediated longevity. Here, we show that prefoldin 6 (PFD-6), a component of the molecular chaperone prefoldin-like complex, relays longevity response from HSF-1 to FOXO under reduced IIS. We found that PFD-6 was specifically required for reduced IIS-mediated longevity by acting in the intestine and hypodermis. We showed that HSF-1 increased the levels of PFD-6 proteins, which in turn directly bound FOXO and enhanced its transcriptional activity. Our work suggests that the prefoldin-like chaperone complex mediates longevity response from HSF-1 to FOXO to increase the life span in animals with reduced IIS.