Mitoregulin modulates inflammation in osteoarthritis: Insights from synovial transcriptomics and cellular studies.

Osteoarthritis is a prevalent musculoskeletal disease that involves cartilage degradation, subchondral bone remodeling, and synovial inflammation and ultimately causes physical disability. Common risk factors for osteoarthritis include age, sex, obesity, and genetic predispositions. Treatment includes nonpharmaceutical and pharmacological approaches; however, disease-modifying osteoarthritis drugs remain undeveloped. We aimed to identify key regulatory factors underlying the etiology of osteoarthritis. We studied alterations of the inflammatory responses after manipulating the expression of MTLN, which we selected after sequencing and transcriptomics of the patients' synovial tissues. MTLN expression was increased in synovial tissues of patients and in SW982 human synovial sarcoma cells following inflammatory stimuli. We found that MTLN overexpression or knockout respectively decreased or increased expression of the inflammation-associated genes, including IL-6, IL-8, and TNF-α. Thus, high levels of MTLN in osteoarthritis may protect tissues against excessive inflammation, thereby offering therapeutic potentials.

Piperlongumine regulates genes involved in the skin barrier in epidermal keratinocyte HaCaT cells.

Given that the skin is the largest tissue in the human body, performing external barrier functions with innate and adaptive immunity and undergoing substantial changes during aging, it is under investigation as a major target of various bioactive molecules. In the present study, we examined the biological activity of the senolytic piperlongumine by analyzing alterations in mRNA expression of notable skin genes using transformed aneuploid immortal epidermal keratinocytes, HaCaT cells. We observed that piperlongumine increased the mRNA expression of genes playing critical roles in skin barrier function. In addition, piperlongumine increased expression enzymes involved in the synthesis of ceramide, a major component of intercellular lipids. Furthermore, we measured the protein levels of various cytokines secreted by epidermal keratinocytes and found changes in the release of GRO-αßγ, CCL5, and MCP1. Additionally, we observed that piperlongumine treatment modulated the expression of keratinocyte-specific aging markers and influenced telomerase activity. Based on these findings, piperlongumine could regulate the physiological activity of epidermal keratinocytes to induce beneficial effects in human skin by regulating important skin-related genes.

Aerobic Exercise Improves Radiation Therapy Efficacy in Non-Small Cell Lung Cancer: Preclinical Study Using a Xenograft Mouse Model.

The "oxygen effect" improves radiation efficacy; thus, tumor cell oxygen concentration is a crucial factor for improving lung cancer treatment. In the current study, we aimed to identify aerobic exercise-induced changes in oxygen concentrations in non-small cell lung cancer (NSCLC) cells. To this end, an NSCLC xenograft mouse model was established using human A549 cells. Animals were subsequently subjected to aerobic exercise and radiation three times per week for 2 weeks. Aerobic exercise was performed at a speed of 8.0 m/m for 30 min, and the tumor was irradiated with 2 Gy of 6 MV X-rays (total radiation dose 12 Gy). Combined aerobic exercise and radiation reduced NSCLC cell growth. In addition, the positive effect of aerobic exercise on radiation efficacy through oxygenation of tumor cells was confirmed based on hypoxia-inducible factor-1 and carbonic anhydrase IX expression. Finally, whole-transcriptome analysis revealed the key factors that induce oxygenation in NSCLC cells when aerobic exercise was combined with radiation. Taken together, these results indicate that aerobic exercise improves the effectiveness of radiation in the treatment of NSCLC. This preclinical study provides a basis for the clinical application of aerobic exercise to patients with NSCLC undergoing radiation therapy.

Development of a Cardiopulmonary Exercise Test Protocol Using Aquatic Treadmill in Healthy Adults: A Pilot Study.

Traditional cardiopulmonary exercise test (CPET) protocols are difficult to apply to patients who have difficulty walking on a treadmill. Therefore, this study aimed to develop an aquatic treadmill (AT) CPET protocol involving constant increments in exercise load (metabolic equivalents (METs)) at regular intervals. Fourteen healthy male participants were enrolled in this study. The depth of the water pool was set to the umbilicus level of each participant, and the water temperature was maintained at 28−29 °C. The testing protocol comprised a total of 12 stages at different speeds. The starting speed was 0.7 km/h, which was increased by 0.6 or 0.7 km/h every 2 min. Heart rate, blood pressure, oxygen uptake, minute ventilation, respiratory exchange ratio, and rate of perceived exertion were recorded at each stage. All values showed a significant increasing trend with stage progression (p < 0.001). Peak oxygen uptake and heart rate values were 29.76 ± 3.75 and 168.36 ± 13.12, respectively. We developed a new AT CPET protocol that brings about constant increments in METs at regular intervals. This new AT CPET protocol could be a promising alternative to traditional CPET protocols for patients who experience difficulty walking on a treadmill.

Compressive femoral neuropathy caused by anticoagulant therapy induced retroperitoneal hematoma: A case report.

RATIONALE: Spontaneous retroperitoneal hematomas due to anticoagulant therapy rarely occur. Retroperitoneal hematomas can cause severe pain in the groin, quadriceps femoris muscle weakness, hemodynamic instability, and abdominal distension. They rarely cause compressive neuropathy of the femoral nerve transversing the iliacus muscle. Differential diagnosis is not easy because they have similar clinical features to retroperitoneal hematomas. PATIENT CONCERNS: A 72-year-old female patient whose right arm was stuck in a bookshelf for 5 days developed right cephalic vein thrombosis. After 5 days of intravenous heparin therapy for venous thrombosis, she presented with sudden right groin pain, right leg paresis, hemodynamic instability, and abdominal distension. DIAGNOSIS: Emergency abdominal and pelvic CT showed a large number of hematomas in the bilateral retroperitoneal space with active bleeding of the right lumbar artery. An electrodiagnostic study was performed 2 weeks later to check for neuromuscular damage in the right lower extremity, and right compressive femoral neuropathy was confirmed. INTERVENTIONS: Heparin therapy was discontinued; emergency embolization of the lumbar artery was performed. After 2 weeks, the patient started receiving physical, occupational, and transcutaneous electrical stimulation therapies. OUTCOMES: She became hemodynamically stable after arterial embolization; a significant decrease in hematoma and patency of the femoral nerve was confirmed on follow-up pelvic MRI. After 2 months of comprehensive rehabilitation, the muscle strength of the right leg significantly improved, and the pain disappeared. LESSONS: Although rare, spontaneous retroperitoneal hematomas may occur in patients receiving anticoagulant medications. They may even occur in patients receiving emergency anticoagulant therapy. Compressive femoral neuropathy due to retroperitoneal hematomas should be considered if muscle weakness and groin pain are observed. Early diagnosis and appropriate treatment plan of compressive femoral neuropathy due to retroperitoneal hematoma are helpful for a good prognosis.

Complex regional pain syndrome type II caused by iatrogenic lateral dorsal cutaneous nerve injury: A case report.

RATIONALE: Complex regional pain syndrome (CRPS) is a painful condition classified as type I or II depending on the absence or presence of nerve injury, respectively. Injury to the lateral dorsal cutaneous nerve (LDCN), a branch of the sural nerve, is a rare occurrence observed after a sprain or procedures conducted on the lateral side of the ankle. PATIENT CONCERNS: A 38-year-old female, who had undergone prolotherapy for a sprain in the lateral side of the left ankle 3 months ago, presented with persistent causalgia and dysesthesia around the injection site. DIAGNOSIS: An electrodiagnostic study was conducted, which confirmed that the patient had peripheral neuropathy of the left LDCN. Considering the digital infrared thermal imaging and three-phase bone scan findings and the clinical presentation, the condition was diagnosed as CRPS type II due to iatrogenic LDCN injury according to the Budapest diagnostic criteria for CRPS. INTERVENTIONS: The patient was treated with steroid pulse therapy, physical therapy, and transcutaneous electrical nerve stimulation, as well as nonsteroidal anti-inflammatory drugs, pregabalin, and tricyclic antidepressants. OUTCOMES: After 1 month of treatment, allodynia of the left foot persisted, but the pain reduced from 6 points to 3 points on the numeric rating scale. Partial recovery of amplitude and conduction velocity was confirmed in the follow-up electrodiagnostic study. LESSONS: LDCN injury should be considered in patients who complain of persistent lateral ankle and foot paresthesia or pain after sprain or procedures performed on the lateral side of the ankle. Early diagnosis and treatment can lead to a good prognosis when the LDCN injury has progressed to CRPS.

Impact of chlorogenic acid on modulation of significant genes in dermal fibroblasts and epidermal keratinocytes.

Chlorogenic acid is one of the most abundant polyphenols found in human diet. It is well-documented that chlorogenic acid has a significant impact on human cells, especially in the regulation of inflammation and metabolic processes. However, its role in regulating skin functions, especially with respect to the dermal collagen network or epidermal skin barrier, has not yet been elucidated. Here, we report that chlorogenic acid treatment can induce production of procollagen type I in human dermal fibroblast, Hs68 cell lines. Moreover, this treatment can stimulate upregulation of skin barrier genes, including the ones encoding filaggrin (FLG), involucrin (IVL), and envoplakin (EVPL), in epidermal keratinocytes. Chlorogenic acid also triggered a multifaceted response in the cytokine profile of keratinocytes. Therefore, we suggest that chlorogenic acid can be used to restore the impaired dermal matrix network as well as the epidermal skin barrier.

Feasibility of segmental bioelectrical impedance analysis for mild- to moderate-degree breast cancer-related lymphedema: Correlation with circumferential volume measurement and phase angle.

ABSTRACT: Segmental multi-frequency bioelectrical impedance analysis (s-MFBIA) has been adopted recently to evaluate the volume of breast cancer-related lymphedema (BCRL). This procedure uses the segmental phase angle (s-PhA) as an indicator of cellular integrity. In the smaller-built Asian population, the BCRL often has a small volume difference and can be overlooked by tape circumference volume measurement (TVM). This study aimed to investigate the clinical feasibility of s-MFBIA for the assessment of lymphedema severity compared with TVM and evaluate the association between lymphedema severity and cellular integrity of the affected arm based on s-PhA values for a patient with mild- to moderate-degree BCRL.Segmental PhA and extracellular water (ECW)/total body water (TBW) ratio of bilateral arms were measured using InBody S10, an s-MFBIA device, in 128 BCRL patients. Inter-limb volume ratio was measured using TVM. The inter-limb ECW/TBW ratio was correlated with inter-limb volume ratio. Inter-limb ECW/TBW ratio and inter-limb volume ratio were then correlated with inter-limb PhA ratio to demonstrate the association between lymphedema severity and arm cellular integrity.The inter-limb ECW/TBW ratio and inter-limb volume ratio were positively correlated (r = 0.654, P < .001). The same result was obtained after adjusting for age, body mass index, postoperative survival, and duration of lymphedema (r = 0.636, 0.653, 0.652, and 0.648, P < .001). The inter-limb PhA ratio demonstrated significant negative correlation with inter-limb ECW/TBW ratio and inter-limb volume ratio (r = -0.896, -0.562, P < .001).s-MFBIA has high consistency with the conventional TVM method, and its relation to cellular integrity by segmental PhA enables better understanding of the cellular state of the affected limb in mild- to moderate-degree BCRL. Therefore, it is clinically feasible for severity assessment and monitoring of mild- to moderate-degree BCRL in smaller-built Asian patients.

Comprehensive Respiratory Muscle Training Improves Pulmonary Function and Respiratory Muscle Strength in Acute Stroke Patients.

PURPOSE: To evaluate the effects of respiratory muscle training (RMT) on pulmonary function, respiratory complications, and stroke-related disabilities in patients with acute stroke. METHODS: One hundred twenty-two subjects with stroke admitted to the stroke rehabilitation center of Inje Hospital between August 2016 and May 2018 were recruited. After the initial exclusion, the remaining patients were assigned to the RMT group (36 patients) or the standard rehabilitation (SR) group (28 patients who did not undergo RMT). A total of 44 patients completed the study, with 22 patients in each group. The RMT program consisted of air-stacking exercise, manually assisted coughing, inspiratory and expiratory muscle strengthening, cough exercises, and respiratory reeducation. Pulmonary function and respiratory muscle strength were evaluated before commencement and after 1 mo of RMT. The Functional Ambulation Category score, Korean version of the Modified Barthel Index, Shoulder Abduction and Finger Extension score, and handgrip power were assessed. The incidence of pneumonia was also evaluated. RESULTS: Both pulmonary function and respiratory muscle strength significantly improved in both groups. However, differences (%) in the RMT group was greater for all parameters of pulmonary function and respiratory muscle strength. Respiratory complications at 1 yr were significantly lower in the RMT group (P = .016). CONCLUSION: Four weeks of comprehensive RMT in patients with acute stroke resulted in significantly greater improvements in both pulmonary function and respiratory muscle strength than SR. Therefore, RMT has the potential to reduce post-stroke respiratory complications.

Cognitive Intervention with Musical Stimuli Using Digital Devices on Mild Cognitive Impairment: A Pilot Study.

The effect of music therapy on cognitive function has been widely reported; however, its clinical implications remain controversial. Performing therapeutic musical activities in groups using individualized instruments can help overcome the issues of engagement and compliance. We aimed to evaluate the effect of a cognitive intervention with musical stimuli using digital devices on mild cognitive impairment (MCI). In this prospective study, 24 patients with MCI (intervention group, 12; and control group, 12) were enrolled. We developed an electronic device with musical instruments and the Song-based Cognitive Stimulation Therapy protocol (SongCST). Patients in the intervention group underwent a 10-week cognitive intervention involving musical stimuli generated by our device. Effect of the intervention on cognitive function was evaluated by the Mini-Mental State Examination-Dementia Screening (MMSE-DS), Montreal Cognitive Assessment-Korean (MOCA-K), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB). In the intervention group, MMSE-DS and MOCA-K scores improved significantly after the 10-week intervention. The changes in MOCA-K and CDR-SB scores were significantly different between the intervention and control groups. Our study showed that music therapy with digital devices has a positive effect on the executive function and overall disease severity in patients with MCI. Our study can facilitate individualization of music therapy using digital devices in groups.

Compressive peroneal neuropathy by an intraneural ganglion cyst combined with L5 radiculopathy: A case report.

RATIONALE: Most cases of foot drop are known to result from lower motor neuron pathologies, particularly lumbar radiculopathy and peripheral neuropathy, including common peroneal neuropathy. To improve the prognosis of foot drop, it is important to quickly and accurately diagnose the etiology and provide appropriate treatment. PATIENT CONCERNS: A 65-year-old female patient with a history of L4-5 intervertebral disc herniation presented with right foot drop that had developed 1 month previously. DIAGNOSIS: Electrodiagnostic examination revealed common peroneal neuropathy combined with L5 radiculopathy, with the former being the main cause of the foot drop. MRI of the right knee was performed to identify the cause of the peroneal nerve lesion, which revealed an intraneural ganglion cyst in the common peroneal nerve. INTERVENTIONS: The patient was treated by ultrasound-guided percutaneous cyst aspiration and corticosteroid injection into the decompressed ganglion, followed by strengthening exercise, electrical stimulation therapy, and prescription of an ankle foot orthosis. OUTCOMES: We confirmed regeneration of the injured peroneal nerve at the follow-up electrodiagnostic examination 12 weeks after the intervention. In addition, the manual motor power test demonstrated an increase in the ankle dorsiflexor function score by one grade. LESSONS: Diagnosing the cause of foot drop can be difficult with multiple co-existing pathologies, and consideration of various possible etiologies is the key for appropriate diagnosis and treatment. In addition to imaging modalities such as MRI, electrodiagnostic examination can help to improve diagnostic accuracy. Intraneural ganglion cyst of the common peroneal nerve is rare, but should be considered as a possible cause of foot drop.

Characteristics and Clinical Course of Dysphagia Caused by Anterior Cervical Osteophyte.

OBJECTIVE: To investigate swallowing characteristics of patients with dysphagia caused by anterior cervical osteophytes (ACOs) and compare clinical courses according to treatment options. METHODS: A retrospective analysis of 1,866 videofluoroscopic swallowing studies (VFSS) of patients with ACOs from electronic medical records was performed. Patients with other diseases that could explain the dysphagia were excluded. Dysphagia characteristics and severity and clinical and radiological characteristics of subjects with ACOs were evaluated. Dysphagia characteristics and clinical course were compared among three treatment groups: surgical treatment, swallowing rehabilitation, and conservative treatment. RESULTS: Subjects were 22 men and 1 woman with a mean age of 78.69±8.01 years. The mean osteophyte thickness was 9.07±3.84 mm. It was significantly thicker in the surgical group than that in other groups (p=0.01). ACOs were most frequently found at C5 level. This level also had the thickest osteophytes. However, videofluoroscopic dysphagia scales (VDS) were not significantly different among the three treatment groups. The pharyngeal phase score of the VDS was significantly higher in the surgical group (p=0.041). Dysphagia severity was decreased significantly in the surgical group at 3 months after the initial VFSS (p=0.004). CONCLUSION: The main swallowing characteristics in patients with ACOs were dysphagia features of the pharyngeal phase, including inappropriate airway protection, decreased laryngeal elevation, and reduced epiglottis inversion. When determining treatment options, it may be helpful to consider dysphagia severity at pharyngeal phase and osteophyte thickness.

Botulinum Toxin-A Injection in the Treatment of Spasticity in a Infantile-Onset Neurodegeneration With Brain Iron Accumulation: A Case Report.

Pantothenate kinase-associated neurodegeneration (PKAN) is a neurodegenerative disorder characterized by iron accumulation in the globus pallidus (GP) of the brain (neurodegeneration with brain iron accumulation [NBIA]), which is characterized by dystonia and spasticity resulting in postural difficulties. A 33-month-old boy was admitted with a pronounced gait disturbance. Marked hypertonicity in the patient's both calf muscles was noted, resulting in waddling with repeated slip-falls. NBIA was suspected by high T2 intensity in the GP on brain MRI, then it was confirmed by detecting PANK2 mutation. Botulinum toxin-A injection was administered to both calf muscles. After 2 weeks, a decrease in spasticity and an increase in range of motion were observed, and consequently, an increase in the patient's gait stability with both heels touching the ground, enabling him to walk straight independently. A definitive treatment for NBIA has not been established, and a symptomatic therapy is currently the mainstay of treatment in this case. This is the first case report of botulinum toxin injection for treatment of gait disturbance caused by spasticity in an infantile-onset PKAN.

Efficacy of Aquatic Treadmill Training on Gait Symmetry and Balance in Subacute Stroke Patients.

OBJECTIVE: To determine the efficacy of aquatic treadmill training (ATT) as a new modality for stroke rehabilitation, by assessing changes in gait symmetry, balance function, and subjective balance confidence for the paretic and non-paretic leg in stroke patients. METHODS: Twenty-one subacute stroke patients participated in 15 intervention sessions of aquatic treadmill training. The Comfortable 10-Meter Walk Test (CWT), spatiotemporal gait parameters, Berg Balance Scale (BBS), and Activities-specific Balance Confidence scale (ABC) were assessed pre- and post-interventions. RESULTS: From pre- to post-intervention, statistically significant improvements were observed in the CWT (0.471±0.21 to 0.558±0.23, p<0.001), BBS (39.66±8.63 to 43.80±5.21, p<0.001), and ABC (38.39±13.46 to 46.93±12.32, p<0.001). The step-length symmetry (1.017±0.25 to 0.990±0.19, p=0.720) and overall temporal symmetry (1.404±0.36 to 1.314±0.34, p=0.218) showed improvement without statistical significance. CONCLUSION: ATT improves the functional aspects of gait, including CWT, BBS and ABC, and spatiotemporal gait symmetry, though without statistical significance. Further studies are required to examine and compare the potential benefits of ATT as a new modality for stroke therapy, with other modalities.