Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors target SGLT2 in renal proximal tubules and promote glycosuria in type 2 diabetes mellitus in humans and animal models, resulting in reduced blood glucose levels. Although clinical trials have shown that SGLT2 inhibitors attenuate the progression of chronic kidney disease, there have been concerns regarding SGLT2-induced acute kidney injury. In this study, we investigated the effect of SGLT2 inhibitors on adriamycin-induced kidney injury in mice. METHODS: Seven-week-old balb/c mice were injected with adriamycin 11.5 mg/kg via the tail vein. Additionally, dapagliflozin was administered via gavage for 2 weeks. The mice were divided into five groups: vehicle, dapagliflozin 3 mg/kg, adriamycin, adriamycin plus dapagliflozin 1 mg/kg, and adriamycin plus dapagliflozin 3 mg/kg. RESULTS: Adriamycin injection reduced the body weight and food and water intakes. Dapagliflozin also decreased the body weight and food and water intakes. Fasting blood glucose and urine volume were not altered by either adriamycin or dapagliflozin. Once adriamycin-induced kidney injury had developed, there were no differences in systolic blood pressure among the groups. Dapagliflozin did not alleviate proteinuria in adriamycin-induced kidney injury. Adriamycin induced significant glomerular and interstitial injury, but dapagliflozin did not attenuate these changes in renal injury. Interestingly, SGLT2 expressions were different between the cortex and medulla of kidneys by dapagliflozin treatment. Dapagliflozin increased SGLT2 expression in medulla, not in cortex. CONCLUSION: Dapagliflozin had no effect on proteinuria or inflammatory changes such as glomerular and tubular damages in adriamycin-induced kidney injury. Our study suggests that dapagliflozin does not protect against adriamycin-induced kidney injury. More experimental studies regarding the effects of SGLT2 inhibitors on various kidney diseases are needed to clarify the underlying mechanisms.

Assessment of oral hypofunction and its association with age among Korean community-dwelling older adults.

BACKGROUND: Due to the increasing proportion of older adults in Korea and growing interest in aging, the concepts of oral aging and oral hypofunction have recently been introduced. Thus, it is necessary to investigate the age-specific oral function levels of Korean older adults and develop expert intervention methods for healthy aging. METHODS: Dysphagia, independence of daily living, and oral hypofunction were assessed in 206 older adults living in Wonju, Gangwon State, South Korea. Subjective dysphagia was assessed through self-report questionnaires using the Dysphagia Handicap Index (DHI), the Korean version of Eating Assessment Tool-10, and the Korean version of the Modified Barthel Index. In addition, the oral hypofunction assessment items included decreased chewing ability, occlusal pressure, tongue pressure, oral dryness, and oral cleanliness. RESULTS: DHI increased significantly with age, with those in their 80 s reporting the most difficulty swallowing. Oral function in terms of chewing ability (maximum occlusal pressure and number of remaining teeth), maximum occlusal pressure, and maximum tongue pressure also declined with increasing age. While there was no significant difference in oral dryness by age, those in their 80 s had dry mouth according to the criteria of the oral moisture checking device. CONCLUSIONS: In an assessment of oral function in community-dwelling, independent Korean older adults, the number of items that were assessed as oral hypofunction increased with age. The findings can be used to standardize the oral hypofunction assessment item and develop age-based individualized intervention plans for the early management of oral health and individual oral myofunctional rehabilitation in Korean community-dwelling older adults.

The impact of depression, stress, and self-esteem on quality of life among older adults in South Korea.

Background & Objective: Aging is a global trend, and Korea is also entering an aging society, which threatens the mental health of the elderly due to isolation, etc. In line with the growing domestic and international interest in elderly issues, this study aimed to identify the effects of depression, stress and self-esteem on the lives of the elderly in South Korea and to provide basic data for welfare measures. Methods: Depression, stress, self-esteem, and quality of life were measured in 104 South Korean seniors (32 men, 72 women, average age 72.94 years old). Differences between groups according to gender and residence type were confirmed. Results: There were no significant differences in stress among the elderly by place of residence, but there were significant differences in quality of life, depression, and self-esteem. Quality of life and self-esteem were higher in private housing than in public housing, and depression was higher in public housing than in private housing. In addition, lower depression and higher self-esteem were correlated with higher quality of life among the elderly. Conclusion: With the global trend of an aging society, it is essential to continue to pay attention to assist the lives of elderly and provide them with practical support and policies. The quality of life of the elderly requires continuous attention and efforts to support and policies for mental health and economic support.

Vacancies in growing habitats promote the evolution of cooperation.

We study evolutionary game dynamics in a growing habitat with vacancies. Fitness is determined by the global effect of the environment and a local prisoner's dilemma among neighbors. We study population growth on a one-dimensional lattice and analyze how the environment affects evolutionary competition. As the environment becomes harsh, an absorbing phase transition from growing populations to extinction occurs. The transition point depends on which strategies are present in the population. In particular, we find a 'cooperative window' in parameter space, where only cooperators can survive. A mutant defector in a cooperative community might briefly proliferate, but over time naturally occurring vacancies separate cooperators from defectors, thereby driving defectors to extinction. Our model reveals that vacancies provide a strong boost for cooperation by spatial selection.

Bacterial neurotoxic metabolites in multiple sclerosis cerebrospinal fluid and plasma.

The identification of intestinal dysbiosis in patients with neurological and psychiatric disorders has highlighted the importance of gut-brain communication, and yet the question regarding the identity of the components responsible for this cross-talk remains open. We previously reported that relapsing remitting multiple sclerosis patients treated with dimethyl fumarate have a prominent depletion of the gut microbiota, thereby suggesting that studying the composition of plasma and CSF samples from these patients may help to identify microbially derived metabolites. We used a functional xenogeneic assay consisting of cultured rat neurons exposed to CSF samples collected from multiple sclerosis patients before and after dimethyl fumarate treatment to assess neurotoxicity and then conducted a metabolomic analysis of plasma and CSF samples to identify metabolites with differential abundance. A weighted correlation network analysis allowed us to identify groups of metabolites, present in plasma and CSF samples, whose abundance correlated with the neurotoxic potential of the CSF. This analysis identified the presence of phenol and indole group metabolites of bacterial origin (e.g. p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) as potentially neurotoxic and decreased by treatment. Chronic exposure of cultured neurons to these metabolites impaired their firing rate and induced axonal damage, independent from mitochondrial dysfunction and oxidative stress, thereby identifying a novel pathway of neurotoxicity. Clinical, radiological and cognitive test metrics were also collected in treated patients at follow-up visits. Improved MRI metrics, disability and cognition were only detected in dimethyl fumarate-treated relapsing remitting multiple sclerosis patients. The levels of the identified metabolites of bacterial origin (p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) were inversely correlated to MRI measurements of cortical volume and directly correlated to the levels of neurofilament light chain, an established biomarker of neurodegeneration. Our data suggest that phenol and indole derivatives from the catabolism of tryptophan and phenylalanine are microbially derived metabolites, which may mediate gut-brain communication and induce neurotoxicity in multiple sclerosis.

Translation of the intrinsically disordered protein α-synuclein is inhibited by a small molecule targeting its structured mRNA.

Many proteins are refractory to targeting because they lack small-molecule binding pockets. An alternative to drugging these proteins directly is to target the messenger (m)RNA that encodes them, thereby reducing protein levels. We describe such an approach for the difficult-to-target protein α-synuclein encoded by the SNCA gene. Multiplication of the SNCA gene locus causes dominantly inherited Parkinson's disease (PD), and α-synuclein protein aggregates in Lewy bodies and Lewy neurites in sporadic PD. Thus, reducing the expression of α-synuclein protein is expected to have therapeutic value. Fortuitously, the SNCA mRNA has a structured iron-responsive element (IRE) in its 5' untranslated region (5' UTR) that controls its translation. Using sequence-based design, we discovered small molecules that target the IRE structure and inhibit SNCA translation in cells, the most potent of which is named Synucleozid. Both in vitro and cellular profiling studies showed Synucleozid directly targets the α-synuclein mRNA 5' UTR at the designed site. Mechanistic studies revealed that Synucleozid reduces α-synuclein protein levels by decreasing the amount of SNCA mRNA loaded into polysomes, mechanistically providing a cytoprotective effect in cells. Proteome- and transcriptome-wide studies showed that the compound's selectivity makes Synucleozid suitable for further development. Importantly, transcriptome-wide analysis of mRNAs that encode intrinsically disordered proteins revealed that each has structured regions that could be targeted with small molecules. These findings demonstrate the potential for targeting undruggable proteins at the level of their coding mRNAs. This approach, as applied to SNCA, is a promising disease-modifying therapeutic strategy for PD and other α-synucleinopathies.

The Impact of a Mobile Support Group on Distress and Physical Activity in Breast Cancer Survivors: Randomized, Parallel-Group, Open-Label, Controlled Trial.

BACKGROUND: While mobile health apps have demonstrated their potential in revolutionizing health behavior changes, the impact of a mobile community built on these apps on the level of physical activity and mental well-being in cancer survivors remains unexplored. OBJECTIVE: In this randomized controlled trial, we examine the effects of participation in a mobile health community specifically designed for breast cancer survivors on their physical activity levels and mental distress. METHODS: We performed a single-center, randomized, parallel-group, open-label, controlled trial. This trial enrolled women between 20 and 60 years of age with stage 0 to III breast cancer, an Eastern Cooperative Oncology Group performance status of 0, and the capability of using their own smartphone apps. From January 7, 2019, to April 17, 2020, a total of 2,616 patients were consecutively screened for eligibility after breast cancer surgery. Overall, 202 patients were enrolled in this trial, and 186 patients were randomly assigned (1:1) to either the intervention group (engagement in a mobile peer support community using an app for tracking steps; n=93) or the control group (using the app for step tracking only; n=93) with a block size of 10 without stratification. The mobile app provides a visual interface of daily step counts, while the community function also provides rankings among its members and regular notifications encouraging physical activity. The primary end point was the rate of moderate to severe distress for the 24-week study period, measured through an app-based survey using the Distress Thermometer. The secondary end point was the total weekly steps during the 24-week period. RESULTS: After excluding dropouts, 85 patients in the intervention group and 90 patients in the control group were included in the analysis. Multivariate analyses showed that patients in the intervention group had a significantly lower degree of moderate to severe distress (B=-0.558; odds ratio 0.572; P<.001) and a higher number of total weekly step counts (B=0.125; rate ratio 1.132; P<.001) during the 24-week period. CONCLUSIONS: Engagement in a mobile app-based patient community was effective in reducing mental distress and increasing physical activity in breast cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT03783481; https://classic.clinicaltrials.gov/ct2/show/NCT03783481.

Invasion and interaction determine population composition in an open evolving ecological system.

It is well-known that interactions between species determine the population composition in an ecosystem. Conventional studies have focused on fixed population structures to reveal how interactions shape population compositions. However, interaction structures are not fixed but change over time due to invasions. Thus, invasion and interaction play an important role in shaping communities. Despite its importance, however, the interplay between invasion and interaction has not been well explored. Here, we investigate how invasion affects the population composition with interactions in open evolving ecological systems considering generalized Lotka-Volterra-type dynamics. Our results show that the system has two distinct regimes. One is characterized by low diversity with abrupt changes of dominant species in time, appearing when the interaction between species is strong and invasion slowly occurs. On the other hand, frequent invasions can induce higher diversity with slow changes in abundances despite strong interactions. It is because invasion happens before the system reaches its equilibrium, which drags the system from its equilibrium all the time. All species have similar abundances in this regime, which implies that fast invasion induces regime shift. Therefore, whether invasion or interaction dominates determines the population composition.

Feasibility of facial nerve monitoring using adhesive surface electrodes during parotidectomy: a comparative study with needle electrodes.

PURPOSE: Electrophysiological monitoring of the facial nerve during parotidectomy has been reported as an adjunctive method to prevent facial nerve injury. Classically, a needle electrode is used to obtain electromyographic (EMG) signals from facial muscles during facial nerve monitoring (FNM) of parotid surgery, likewise adhesive surface electrodes. This study aimed to investigate the feasibility of performing FNM with surface electrodes during parotid surgery and to compare EMG values with needle electrodes. METHODS: Thirty patients who underwent parotidectomy under FNM using adhesive surface and needle electrodes were included. Two pairs of adhesive surface electrodes and needle electrodes were used for FNM during parotid surgery. Mean amplitudes were collected after electrical facial nerve stimulation at 1 mA after specimen removal. RESULTS: The mean amplitude of the adhesive surface electrodes was 226.50 ± 118.44 µV (orbicularis oculi muscle) and 469.6 ± 306.06 µV (orbicularis oris muscle), respectively. The mean amplitude of the needle electrodes was 449.85 ± 248.10 µV (orbicularis oculi muscle) and 654.66 ± 395.71 µV (orbicularis oris muscle), respectively. The mean amplitude of the orbicularis oris muscle was significantly greater than that of the orbicularis oculi. The amplitude values measured in the orbicularis oculi muscle showed significant differences between the needle and skin electrodes. CONCLUSIONS: Facial nerve monitoring (FNM) using adhesive surface electrodes is feasible in parotid surgery. Although the mean amplitude value of the surface electrode was relatively lower than that of the needle electrode, the surface electrode is considered a feasible and safe EMG recording device for FNM in parotid surgery.

ssFPN: Scale Sequence (S2) Feature-Based Feature Pyramid Network for Object Detection.

Object detection is a fundamental task in computer vision. Over the past several years, convolutional neural network (CNN)-based object detection models have significantly improved detection accuracyin terms of average precision (AP). Furthermore, feature pyramid networks (FPNs) are essential modules for object detection models to consider various object scales. However, the AP for small objects is lower than the AP for medium and large objects. It is difficult to recognize small objects because they do not have sufficient information, and information is lost in deeper CNN layers. This paper proposes a new FPN model named ssFPN (scale sequence (S2) feature-based feature pyramid network) to detect multi-scale objects, especially small objects. We propose a new scale sequence (S2) feature that is extracted by 3D convolution on the level of the FPN. It is defined and extracted from the FPN to strengthen the information on small objects based on scale-space theory. Motivated by this theory, the FPN is regarded as a scale space and extracts a scale sequence (S2) feature by three-dimensional convolution on the level axis of the FPN. The defined feature is basically scale-invariant and is built on a high-resolution pyramid feature map for small objects. Additionally, the deigned S2 feature can be extended to most object detection models based on FPNs. We also designed a feature-level super-resolution approach to show the efficiency of the scale sequence (S2) feature. We verified that the scale sequence (S2) feature could improve the classification accuracy for low-resolution images by training a feature-level super-resolution model. To demonstrate the effect of the scale sequence (S2) feature, experiments on the scale sequence (S2) feature built-in object detection approach including both one-stage and two-stage models were conducted on the MS COCO dataset. For the two-stage object detection models Faster R-CNN and Mask R-CNN with the S2 feature, AP improvements of up to 1.6% and 1.4%, respectively, were achieved. Additionally, the APS of each model was improved by 1.2% and 1.1%, respectively. Furthermore, the one-stage object detection models in the YOLO series were improved. For YOLOv4-P5, YOLOv4-P6, YOLOR-P6, YOLOR-W6, and YOLOR-D6 with the S2 feature, 0.9%, 0.5%, 0.5%, 0.1%, and 0.1% AP improvements were observed. For small object detection, the APS increased by 1.1%, 1.1%, 0.9%, 0.4%, and 0.1%, respectively. Experiments using the feature-level super-resolution approach with the proposed scale sequence (S2) feature were conducted on the CIFAR-100 dataset. By training the feature-level super-resolution model, we verified that ResNet-101 with the S2 feature trained on LR images achieved a 55.2% classification accuracy, which was 1.6% higher than for ResNet-101 trained on HR images.

Emergence of Inequality in Income and Wealth Dynamics.

Increasing wealth inequality is a significant global issue that demands attention. While the distribution of wealth varies across countries based on their economic stages, there is a universal trend observed in the distribution function. Typically, regions with lower wealth values exhibit an exponential distribution, while regions with higher wealth values demonstrate a power-law distribution. In this review, we introduce measures that effectively capture wealth inequality and examine wealth distribution functions within the wealth exchange model. Drawing inspiration from the field of econophysics, wealth exchange resulting from economic activities is likened to a kinetic model, where molecules collide and exchange energy. Within this framework, two agents exchange a specific amount of wealth. As we delve into the analysis, we investigate the impact of various factors such as tax collection, debt allowance, and savings on the wealth distribution function when wealth is exchanged. These factors play a crucial role in shaping the dynamics of wealth distribution.

Assessment of optimal renin-angiotensin-system inhibition strategy in Asian patients with STEMI after primary myocardial revascularization.

BACKGROUND: For the Asian patients with STEMI undergoing PCI, ACEIs are known to have a better outcome than ARBs. However, there is limited evidence to suggest so. METHODS: Among the STEMI registry consist of 1142 Korean patients, we compared the MACE, the composite of myocardial infarction, stoke, death, admission for heart failure, and target vessel revascularization, between the ACEI and ARB groups (Set 1). Further, we defined adequate medication as the administration of a dose equal to or higher than the initiation dose of ACEI according to the heart failure guideline recommendation with a mandatory addition of beta-blockers, and compared the outcomes between the inadequate and adequate medication groups (Set 2). Propensity score matching was used to eliminate difference. RESULTS: In the Set 1 comparison, patients in the ACEI group had a better outcome than those in the ARB group for both whole and matched populations (whole and matched population: Cox regression hazard ratio [HR], 0.645 and 0.535; 95% confidence interval [CI], 0.440-0.944 and 0.296-0.967; p = 0.024 and p = 0.039, respectively). In the Set 2 comparison for the whole population, patients in the inadequate medication group had more MACE than those in the adequate medication group (HR, 0.673; 95% CI, 0.459-0.985; p = 0.042). However, no difference was observed after propensity score matching (HR, 1.023; 95% CI, 0.654-1.602; p = 0.919). CONCLUSION: ACEIs might be a better choice than ARBs after primary revascularization. However, this study's findings suggest that early ACEI dose escalation combined with beta-blocker use may not improve prognosis.

Patulous eustachian tube after balloon eustachian tuboplasty in a post-radiation patient.

BACKGROUND: Balloon eustachian tuboplasty (BET) is a minimally invasive surgical treatment that is effective and safe for obstructive eustachian tube dysfunction. However, BET complications include excessive widening of the eustachian tube, causing a patulous eustachian tube (PET). Herein, we report a case of PET following BET in a patient who underwent radiation therapy and reviewed the literature on considerations for reducing complications after BET. CASE PRESENTATION: A 63-year-old woman complained of bilateral ear fullness after concurrent chemoradiation therapy for nasopharyngeal lymphoma. BET was performed on the left side because the left-sided serous otitis media persisted. A left-sided PET was performed two weeks after the BET, along with eustachian tube silicone plug insertion on the left side. The patient became asymptomatic immediately after the surgery, with no recurrence reported after a 12-month follow-up period. CONCLUSIONS: To our knowledge, there has been no report of PET following BET in a post-radiation patient, and it was successfully treated via ET silicone plug insertion.

Carrying Position-Independent Ensemble Machine Learning Step-Counting Algorithm for Smartphones.

Current step-count estimation techniques use either an accelerometer or gyroscope sensors to calculate the number of steps. However, because of smartphones unfixed placement and direction, their accuracy is insufficient. It is necessary to consider the impact of the carrying position on the accuracy of the pedometer algorithm, because of people carry their smartphones in various positions. Therefore, this study proposes a carrying-position independent ensemble step-counting algorithm suitable for unconstrained smartphones in different carrying positions. The proposed ensemble algorithm comprises a classification algorithm that identifies the carrying position of the smartphone, and a regression algorithm that considers the identified carrying position and calculates the number of steps. Furthermore, a data acquisition system that collects (i) label data in the form of the number of steps estimated from the Force Sensitive Resistor (FSR) sensors, and (ii) input data in the form of the three-axis acceleration data obtained from the smartphones is also proposed. The obtained data were used to allow the machine learning algorithms to fit the signal features of the different carrying positions. The reliability of the proposed ensemble algorithms, comprising a random forest classifier and a regression model, was comparatively evaluated with a commercial pedometer application. The results indicated that the proposed ensemble algorithm provides higher accuracy, ranging from 98.1% to 98.8%, at self-paced walking speed than the commercial pedometer application, and the machine learning-based ensemble algorithms can effectively and accurately predict step counts under different smart phone carrying positions.

Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms.

Cancer is the leading cause of mortality worldwide. Various chemotherapeutic drugs have been extensively used for cancer treatment. However, current anticancer drugs cause severe side effects and induce resistance. Therefore, the development of novel and effective anticancer agents with minimal or no side effects is important. Notably, natural compounds have been highlighted as anticancer drugs. Among them, many researchers have focused on mushrooms that have biological activities, including antitumor activity. The aim of this review is to discuss the anticancer potential of different mushrooms and the underlying molecular mechanisms. We provide information regarding the current clinical status and possible modes of molecular actions of various mushrooms and mushroom-derived compounds. This review will help researchers and clinicians in designing evidence-based preclinical and clinical studies to test the anticancer potential of mushrooms and their active compounds in different types of cancers.

Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson's disease and DLB.

Hyperphosphorylated α-synuclein in Lewy bodies and Lewy neurites is a characteristic neuropathological feature of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). The catalytic subunit of the specific phosphatase, protein phosphatase 2A (PP2A) that dephosphorylates α-synuclein, is hypomethylated in these brains, thereby impeding the assembly of the active trimeric holoenzyme and reducing phosphatase activity. This phosphatase deficiency contributes to the accumulation of hyperphosphorylated α-synuclein, which tends to fibrillize more than unmodified α-synuclein. Eicosanoyl-5-hydroxytryptamide (EHT), a fatty acid derivative of serotonin found in coffee, inhibits the PP2A methylesterase so as to maintain PP2A in a highly active methylated state and mitigates the phenotype of α-synuclein transgenic (SynTg) mice. Considering epidemiologic and experimental evidence suggesting protective effects of caffeine in PD, we sought, in the present study, to test whether there is synergy between EHT and caffeine in models of α-synucleinopathy. Coadministration of these two compounds orally for 6 mo at doses that were individually ineffective in SynTg mice and in a striatal α-synuclein preformed fibril inoculation model resulted in reduced accumulation of phosphorylated α-synuclein, preserved neuronal integrity and function, diminished neuroinflammation, and improved behavioral performance. These indices were associated with increased levels of methylated PP2A in brain tissue. A similar profile of greater PP2A methylation and cytoprotection was found in SH-SY5Y cells cotreated with EHT and caffeine, but not with each compound alone. These findings suggest that these two components of coffee have synergistic effects in protecting the brain against α-synuclein-mediated toxicity through maintenance of PP2A in an active state.

Germinated Rhynchosia nulubilis Fermented with Lactobacillus pentosus SC65 Reduces Particulate Matter Induced Type II Alveolar Epithelial Apoptotic Cell Death.

Particulate matter (PM) is a significant environmental pollutant that promotes respiratory diseases, including lung injury and inflammation, by inducing oxidative stress. Rhynchosia nulubilis (black soybean) is traditionally used to prevent chronic respiratory disease via inducing antioxidant and anti-inflammatory effects. To investigate the effects of Lactobacillus pentosus SC65 fermented GR (GR-SC65) and Pediococcus pentosaceus ON81A (GR-ON81A) against PM-induced oxidative stress and cell death in A549 cells, we performed the 2-7-dichlorodihydrofluorescein diacetate and cell counting kit-8 assays, as well as Hoechst 33342 and propidium iodide staining and western blotting. GR-SC65 showed the highest total polyphenolic contents and 1,1-diphenyl-2-picrylidrazil radical scavenging activity among lactic acid bacteria-fermented GRs (p < 0.001 vs. GR). Four soy peptides, ß-conglycinin breakdowns (INAENNQRNF, ISSEDKPFN, LAFPGSAQAVEK, and LAFPGSAKDIEN), were detected in GR-SC65, but not in GR. In GR-SC65, PM-induced A549 cell death was less than that observed in GR-ON81A and GR (p < 0.001 vs. PM-treated group). GR-SC65 significantly decreased intracellular reactive oxidative species (ROS) when compared with PM (*** p < 0.001 vs. PM). GR-SC65 decreased the levels of BAX, active caspase-9, -3, and poly ADP-ribose polymerase (PARP) proteins (#p < 0.01, ###p < 0.001 vs. PM), while increasing the level of BCL-2 protein, a mitochondrial anti-apoptotic protein (###p < 0.001 vs. PM). Our findings indicate that GR-SC65 inhibited PM-induced cell death by suppressing the levels of ROS, active caspase-9 and -3, and PARP proteins, while enhancing the level of BCL-2 protein in type II alveolar epithelial A549 cells. Therefore, GR-SC65 might be a potential therapeutic and preventive agent against PM-induced lung injury.

Therapeutic Effects of Aripiprazole in the 5xFAD Alzheimer's Disease Mouse Model.

Global aging has led to growing health concerns posed by Alzheimer's disease (AD), the most common type of dementia. Aripiprazole is an atypical FDA-approved anti-psychotic drug with potential against AD. To investigate its therapeutic effects on AD pathology, we administered aripiprazole to 5xFAD AD model mice and examined beta-amyloid (ßA)-induced AD-like phenotypes, including ßA production, neuroinflammation, and cerebral glucose metabolism. Aripiprazole administration significantly decreased ßA accumulation in the brains of 5xFAD AD mice. Aripiprazole significantly modified amyloid precursor protein processing, including carboxyl-terminal fragment ß and ßA, a disintegrin and metalloproteinase domain-containing protein 10, and beta-site APP cleaving enzyme 1, as determined by Western blotting. Neuroinflammation, as evidenced by ionized calcium binding adapter molecule 1 and glial fibrillary acidic protein upregulation was dramatically inhibited, and the neuron cell layer of the hippocampal CA1 region was preserved following aripiprazole administration. In 18F-fluorodeoxyglucose positron emission tomography, after receiving aripiprazole, 5xFAD mice showed a significant increase in glucose uptake in the striatum, thalamus, and hippocampus compared to vehicle-treated AD mice. Thus, aripiprazole effectively alleviated ßA lesions and prevented the decline of cerebral glucose metabolism in 5xFAD AD mice, suggesting its potential for ßA metabolic modification and highlighting its therapeutic effect over AD progression.

Intraoperative botulinum toxin injection for superficial partial parotidectomy: A prospective pilot study.

OBJECTIVES: Sialocele and salivary fistula are not serious but troublesome complications after parotidectomy. Various modalities have been introduced to prevent postoperative saliva-related complications. However, clinical trials assessing the prophylactic use of botulinum toxin (BTX) for parotidectomy have not been conducted yet. Herein, we report a pilot study investigating the safety and efficacy of intraoperative BTX (iBTX) injection in partial superficial parotidectomy (PSP). PARTICIPANTS: Patients with benign parotid tumour were prospectively recruited for this clinical trial from 2017 to 2019. The study participants underwent PSP with iBTX injection. We retrospectively reviewed the clinical information of all the consecutive patients who underwent PSP without iBTX from 2013 to 2019. These patients were divided into two groups: the iBTX group (n = 36) and the control group (n = 54). RESULTS: Permanent facial palsy was not observed in either group. Two patients (3.7%) had transient marginal palsy in the control group but none had it in the iBTX group. The incidence of sialocele was significantly lower in the iBTX group than in the control group (2.8% vs. 20.4%, P < .05). Although the incidence of salivary fistula was lower in the iBTX group than in the control group (0% vs. 7.4%), no significant difference was determined between the two groups (P = .147). Total drainage volume was significantly lower in the iBTX group than in the control group (55.0 mL vs. 116.6 mL, P < .001). CONCLUSIONS: iBTX injection may be safe and effective in reducing sialocele and postoperative drainage in PSP. It might be a useful option to prevent saliva-related complications after PSP.

A metabolic perspective on CSF-mediated neurodegeneration in multiple sclerosis.

Multiple sclerosis is an autoimmune demyelinating disorder of the CNS, characterized by inflammatory lesions and an underlying neurodegenerative process, which is more prominent in patients with progressive disease course. It has been proposed that mitochondrial dysfunction underlies neuronal damage, the precise mechanism by which this occurs remains uncertain. To investigate potential mechanisms of neurodegeneration, we conducted a functional screening of mitochondria in neurons exposed to the CSF of multiple sclerosis patients with a relapsing remitting (n = 15) or a progressive (secondary, n = 15 or primary, n = 14) disease course. Live-imaging of CSF-treated neurons, using a fluorescent mitochondrial tracer, identified mitochondrial elongation as a unique effect induced by the CSF from progressive patients. These morphological changes were associated with decreased activity of mitochondrial complexes I, III and IV and correlated with axonal damage. The effect of CSF treatment on the morphology of mitochondria was characterized by phosphorylation of serine 637 on the dynamin-related protein DRP1, a post-translational modification responsible for unopposed mitochondrial fusion in response to low glucose conditions. The effect of neuronal treatment with CSF from progressive patients was heat stable, thereby prompting us to conduct an unbiased exploratory lipidomic study that identified specific ceramide species as differentially abundant in the CSF of progressive patients compared to relapsing remitting multiple sclerosis. Treatment of neurons with medium supplemented with ceramides, induced a time-dependent increase of the transcripts levels of specific glucose and lactate transporters, which functionally resulted in progressively increased glucose uptake from the medium. Thus ceramide levels in the CSF of patients with progressive multiple sclerosis not only impaired mitochondrial respiration but also decreased the bioavailability of glucose by increasing its uptake. Importantly the neurotoxic effect of CSF treatment could be rescued by exogenous supplementation with glucose or lactate, presumably to compensate the inefficient fuel utilization. Together these data suggest a condition of 'virtual hypoglycosis' induced by the CSF of progressive patients in cultured neurons and suggest a critical temporal window of intervention for the rescue of the metabolic impairment of neuronal bioenergetics underlying neurodegeneration in multiple sclerosis patients.