Common Disease Research Articles

The protective role of phlorizin against lipopolysaccharide-induced acute orchitis in mice associated with changes in gut microbiota composition

ObjectiveOrchitis is a common reproductive disease of male animals, which has serious implications to human and animal reproduction. Additionally, phlorizin (PHN), a common polyphenol in apples and strawberries, has a variety of biological activities, including antioxidant, anti-inflammatory, anti-diabetic, and anti-aging activities. We aimed to determine the protective effects and potential mechanisms of PHN in lipopolysaccharide (LPS)-induced acute orchitis in mice.MethodAfter 21 days of PHN pretreatment, mice were injected with LPS to induce testicular inflammation, and then the changes of testicular tissue structure, expression of inflammatory factors, testosterone level, expression of testosterone-related genes, adhesion gene and protein expression were detected, and the structural changes in the intestinal flora after PHN treatment were further detected by 16SRNA.ResultOur results demonstrated that PHN treatment reduced LPS-induced testicular injury and body and testicular weight losses. The mRNA expression levels of pro-inflammatory cytokines-related genes and antioxidant enzyme activity were also decreased and elevated, respectively, by PHN administration; however, PHN treatment also reduced the LPS-induced decrease in testosterone levels in the testes. Additionally, further studies found that PHN increased the expression of marker proteins zonula occludens-1 (ZO-1) and occludin associated with the blood testosterone barrier compared with that in LPS treatment groups. To further examine the potential mechanisms of the protective effect of PHN on LPS-induced testicular injury, we compared the differences of gut microbiota compositions between the 100 mg/kg PHN treatment group and the control group using 16SRNA. Metagenomic analyses indicated that the abundances of Bacteroidetes, Muribaculaceae, Lactobacillaceae, uncultured bacterium f Muribaculaceae, and Lactobacillus in the PHN treatment group improved, while potential microbes that can induce intestinal diseases, including Verrucomicrobia, Epsilonbacteraeota, Akkermansiaceae, and Akkermansia decreased in the PHN treatment group.ConclusionOur results indicate that PHN pretreatment might alleviate orchitis by altering the composition of gut microflora, which may provide a reference for reducing the occurrence of acute orchitis in male animals.

Predicting mixed venous oxygen saturation (SvO2) impairment in COPD patients using clinical-CT radiomics data: A preliminary study.

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic airway diseases in the world. To predict the degree of mixed venous oxygen saturation (SvO2) impairment in patients with COPD by modeling using clinical-CT radiomics data and to provide reference for clinical decision-making. A total of 236 patients with COPD diagnosed by CT and clinical data at Xiangyang No. 1 People's Hospital (n= 157) and Xiangyang Central Hospital (n= 79) from June 2018 to September 2021 were retrospectively analyzed. The patients were divided into group A (SvO⩾2 62%, N= 107) and group B (SvO<2 62%, N= 129). We set up training set and test set at a ratio of 7/3 and time cutoff spot; In training set, Logistic regression was conducted to analyze the differences in general data (e.g. height, weight, systolic blood pressure), laboratory indicators (e.g. arterial oxygen saturation and pulmonary artery systolic pressure), and CT radiomics (radscore generated using chest CT texture parameters from 3D slicer software and LASSO regression) between these two groups. Further the risk factors screened by the above method were used to establish models for predicting the degree of hypoxia in COPD, conduct verification in test set and create a nomogram. Univariate analysis demonstrated that age, smoking history, drinking history, systemic systolic pressure, digestive symptoms, right ventricular diameter (RV), mean systolic pulmonary artery pressure (sPAP), cardiac index (CI), pulmonary vascular resistance (PVR), 6-min walking distance (6MWD), WHO functional classification of pulmonary hypertension (WHOPHFC), the ratio of forced expiratory volume in the first second to the forced vital capacity (FEV1%), and radscore in group B were all significantly different from those in group A (P< 0.05). Multivariate regression demonstrated that age, smoking history, digestive symptoms, 6MWD, and radscore were independent risk factors for SvO2 impairment. The combined model established based on the abovementioned indicators exhibited a good prediction effect [AUC: 0.903; 95%CI (0.858-0.937)], higher than the general clinical model [AUC: 0.760; 95%CI (0.701-0.813), P< 0.05] and laboratory examination-radiomics model [AUC: 0.868; 95%CI (0.818-0.908), P= 0.012]. The newly created nomogram may be helpful for clinical decision-making and benefit COPD patients. SvO2 is an important indicator of hypoxia in COPD, and it is highly related to age, 6MWD, and radscore. The combined model is helpful for early identification of SvO2 impairment and adjustment of COPD treatment strategies.

Clinical Benefits of Therapeutic Interventions Targeting Mitochondria in Parkinson's Disease Patients.

Parkinson's disease is the second most common neurodegenerative disease. Mitochondrial dysfunction has been associated with neurodegeneration in Parkinson's disease, and several treatments targeting mitochondria have been tested in these patients to delay disease progression and tackle disease symptoms. Herein, we review available data from randomised, double-blind clinical studies that have investigated the role of compounds targeting mitochondria in idiopathic Parkinson's disease patients, with a view of providing patients and clinicians with a comprehensive and practical paper that can inform therapeutic interventions in this group of people. A total of 9 compounds have been tested in randomized clinical trials, but only exenatide has shown some promising neuroprotective and symptomatic effects. However, whether this evidence can be translated into daily clinical practice still needs to be confirmed. In conclusion, targeting mitochondrial dysfunction in Parkinson's disease is a promising therapeutic approach, although only one compound has shown a positive effect on Parkinson's disease progression and symptoms. New compounds have been investigated in animal models, and their efficacy needs to be confirmed in humans through robust, randomised, double-blind clinical trials.

Preventive effect of kiwi berry (Actinidia arguta) on loperamide-induced constipation

Constipation is a common intestinal disease. Kiwi berries can effectively prevent constipation. However, studies have yet to be done to determine how kiwi berries prevent constipation. For 2 weeks, mice in this study were continually orally gavaged with kiwi berry, loperamide, or a combination of the two. This study found that the kiwi group's feces had more water than the constipated mice. In addition, kiwi berries can speed up gastrointestinal transit (GI), shorten the time it takes to pass the first dark stool, and dramatically enhance body weight gain. In the interstitial cells of Cajal (ICC) cells and colon tissues, alterations in the protein expression of vasoactive intestinal peptide (VIP), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and aquaporin-3 (AQP3) were found. At 3, 6, and 12 h of ICC cells and mouse colon, the kiwi group’s VIP, cAMP, PKA, and AQP3 protein expression levels were lower than those of the constipated mice. The kiwi berry can decrease the Firmicutes to Bacteroidetes ratio and boost the diversity and quantity of gut microbiota. By influencing the gut microbiota and VIP-cAMP-PKA-AQP3 signaling pathway, kiwi berries prevent constipation.

Auto Diagnosis of Parkinson's Disease Via a Deep Learning Model Based on Mixed Emotional Facial Expressions.

Parkinson's disease (PD) is a common degenerative disease of the nervous system in the elderly. The early diagnosis of PD is very important for potential patients to receive prompt treatment and avoid the aggravation of the disease. Recent studies have found that PD patients always suffer from emotional expression disorder, thus forming the characteristics of "masked faces". Based on this, we thus propose an auto PD diagnosis method based on mixed emotional facial expressions in the paper. Specifically, the proposed method is cast into four steps: Firstly, we synthesize virtual face images containing six basic expressions (i.e., anger, disgust, fear, happiness, sadness, and surprise) via generative adversarial learning, in order to approximate the premorbid expressions of PD patients; Secondly, we design an effective screening scheme to assess the quality of the above synthesized facial expression images and then shortlist the high-quality ones; Thirdly, we train a deep feature extractor accompanied with a facial expression classifier based on the mixture of the original facial expression images of the PD patients, the high-quality synthesized facial expression images of PD patients, and the normal facial expression images from other public face datasets; Finally, with the well-trained deep feature extractor, we thus adopt it to extract the latent expression features for six facial expression images of a potential PD patient to conduct PD/non-PD prediction. To show real-world impacts, we also collected a new facial expression dataset of PD patients in collaboration with a hospital. Extensive experiments are conducted to validate the effectiveness of the proposed method for PD diagnosis and facial expression recognition.

Roseola Infantum: An Updated Review.

Roseola infantum is a common viral disease that occurs during childhood worldwide. The purpose of this article is to familiarize pediatricians with the clinical manifestations, evaluation, diagnosis, and management of roseola infantum. A search was conducted in April, 2022, in PubMed Clinical Queries using the key terms "roseola infantum" OR "exanthem subitum" OR "sixth disease". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. Roseola infantum is a viral illness characterized by high fever that lasts 3 to 4 days, followed by the sudden appearance of rash at defervescence. The disease occurs most frequently in children between 6 months and 2 years of age. Human herpesvirus-6 (HHV-6) is the major cause of roseola infantum, followed by HHV-7. Transmission of the infection most likely results from the asymptomatic shedding of the virus in the saliva of the caregivers or other close contacts. Characteristically, the rash is discrete, rose-pink in color, circular or elliptical, macular or maculopapular, measuring 2 to 3 mm in diameter. The eruption is first seen on the trunk. It then spreads to the neck and proximal extremities. Typically, the rash blanches on pressure and subsides in 2 to 4 days without sequelae. Most children look well otherwise and appear to be happy, active, alert, and playful. The diagnosis is mainly clinical. Febrile seizures occur in 10 to 15 % of children with roseola infantum during the febrile period. In general, serious complications are rare and occur more often in individuals who are immunocompromised. There is no specific treatment. An antipyretic may be used to reduce fever and discomfort. Roseola infantum is generally a benign and self-limited disease. Failure to recognize this condition may result in undue parental fear, unnecessary investigations, delay in treatment for conditions that mimic roseola infantum and complications from roseola infantum, unnecessary treatment of roseola infantum per se, and misuse of healthcare expenditure.

Laser Ablation for Benign and Malignant Thyroid Nodules - A Mini-Literature Review.

Thyroid nodules are a common disease in endocrine clinical practice. They are often benign, asymptomatic, and do not require any treatment. But, in a non-negligible proportion, they can cause local symptoms of compression or esthetic concerns. In the last two decades, the advent of laser ablation (LA) has become a valid alternative to surgery for these nodules. Moreover, LA has also been successfully used to treat small thyroid cancers and neck recurrence. This study aims to review and summarize the published literature regarding LA in the treatment of benign and malignant thyroid nodules. A comprehensive literature search on PubMed from 2000 to 2023 was carried out. The search terms included: thyroid, nodules, laser, cancer, lymph node metastasis, and autonomously functioning nodules. The most relevant investigations in the field were selected. In the last two decades, a very remarkable number of papers consistently demonstrated that LA is able to durably shrink benign nodules on average by about 50%; better results are obtained in spongiform nodules with a volume less than 15 ml; 500 J/ml of tissue should be administered. LA may be a valid option to treat autonomously functioning nodules and papillary thyroid cancers especially if they are <10 mm, and with neck recurrence in patients already submitted to surgery. LA has also been demonstrated to be cost-effective compared to surgical treatment both in benign and malignant lesions, with similar outcomes. Evidence demonstrated that LA is a valid alternative to surgery in benign and malignant thyroid lesions, but also to obtain a successful treatment, a careful selection of the lesion is mandatory.

Guava fruit disease identification based on improved convolutional neural network

Guava fruit cultivation is crucial for Asian economic development, with Indonesia producing 449,970 metric tons between 2022 and 2023. However, technology-based approaches can detect disease symptoms, enhancing production and mitigating economic losses by enhancing quality. In this paper, we introduce an accurate guava fruit disease detection (GFDI) system. It contains the generation of appropriate diseased images and the development of a novel improved convolutional neural network (improved-CNN) that is built depending on the principles of AlexNet. Also, several preprocessing techniques have been used, including data augmentation, contrast enhancement, image resizing, and dataset splitting. The proposed improved-CNN model is trained to identify three common guava fruit diseases using a dataset of 612 images. The experimental findings indicate that the proposed improved-CNN model achieve accuracy 98% for trains and 93% for tests using 0.001 learning rate, the model parameters are decreased by 50,106,831 compared with traditional AlexNet model. The findings of the investigation indicate that the deep learning model improves the accuracy and convergence rate for guava fruit disease prevention.

Saturated Sliding Mode Control Scheme for a New Wearable Back-Support Exoskeleton

Low back pain has been torturing people around the world as a common and chronic disease, the main inducement of which is lumbar disc herniation (LDH). To alleviate patients’ pain noninvasively, this paper proposes a new lumbar spinal rehabilitation exoskeleton. This exoskeleton is composed of two bands connected by four motor-driven piston pushrods, where the range of band can be adjusted to adapt to people with different waistlines. The four pushrods provide support forces to hold the upper body to relieve the burden of lumbar. The joints between pushrods and band are universal pairs and spherical pairs. The whole structure can be regarded as a parallel robot, thus the supporting and waist tracking performance can be determined by motion control effect of pushrods. Considering the motor torque of pushrods is limited, in this paper, a saturated sliding mode control scheme is proposed. Meanwhile, an extended state observer (ESO) is employed to estimate the external disturbance and internal uncertainties, then the estimates of perturbations will be compensated by the feedback scheme. Furthermore, to enhance the disturbance-tracking performance of the ESO an integrated sliding mode observer is proposed to compensate the tracking errors of ESO. The stabilities of controller and observers are proved by Lyapunov stability theory. Finally, a simulation and two experiments are conducted to verify the performance of the proposed controller and the new exoskeleton. The simulation results show that the novel/new controller can drive the new exoskeleton to move along with the desirable trajectory to support the upper body so that alleviating the burden of waist. The results of myoelectricity experiments also show favorable effectiveness of exoskeleton on supporting upper body in different postures. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —this article was inspired by the concerns of low back pain that many people are suffering. Most existing rehabilitation robots tend to focus on supporting lower body and arms, while back-support rehabilitation robots are barely seen. Although we can see a few upper-body supporting robots in sporadic papers, these studies have not proposed a good control scheme yet. Besides, it is difficult to find a rehabilitation robot with simple structure as well as conforming to ergonomics. To resolve the shortcomings of the structure of existing robots and control models, we proposed a completely new rehabilitation robot with novel mechanical structure. Meanwhile, a new saturated sliding mode and novel integrated observer are employed in the position-force control system to enhance the stability and controllability of the whole robot control system. Then, some elaborately designed experiments are conducted to test the proposed robot and the control system. Numerical results demonstrate that the proposed method can significantly increase the trajectory tracking performance and alleviate low back pain.

Yes-associated protein regulates the differentiation and osteoporosis of bone marrow mesenchymal stem cells

Mammalian Yes-associated protein (YAP) is involved in the regulation of various biological behaviors. Osteoporosis (OP) is a common orthopedic disease. However, the role of YAP in the differentiation and osteoporosis of Bone marrow mesenchymal stem cells (BMSCs) is unclear. Ovariectomy (OVX)-induced OP rat model was constructed and YAP plasmid was transfected to detect bone density and alkaline phosphatase (ALP) activity. Rat BMSCs were assigned into 3 groups: sham group, OP group, and YAP group, in which YAP plasmid was transfected followed by analysis of YAP expression by real-time PCR. After 14 days of induction culture, type I collagen, Osterix and FABP4 mRNA expression was detected by real-time PCR along with Wnt5 protein expression by western blot and TGF-β secretion by ELISA. In OP rats, YAP expression was significantly down-regulated and the bone density and ALP activity decreased (P &lt;0.05). YAP transfection in OP rats reversed the changes in OP rats. In OP group, YAP expression was decreased, and type I collagen and Osterix expression decreased, FABP4 expression increased, β-catenin expression and TGF-β secretion decreased (P &lt;0.05). Transfection of YAP plasmid in BMSCs of OP group significantly reversed the above changes (P &lt;0.05). In conclusion, YAP level decreases in OP and up-regulating its expression in BMSCs can promote osteogenic differentiation and inhibit adipogenic differentiation by regulating Tnt5/TGF-β signaling.

Electronic Microscopy aspects of experimentally induced chronic arthritis

Abstract: Introduction: Chronic diseases are responsible for about 38 million deaths annually and represent about 70% of all deaths worldwide. Among these, rheumatoid arthritis is the most common inflammatory rheumatic dis-ease, representing about 10% of all such disorders. Its incidence is approximately 1% of the general popula-tion. Material and method: our study aims to create an experimental model of chronic arthritis on Wistar rats, fe-male sex, to follow the dynamics of joint inflammatory phenomena, the effects of Leflunomide in their evolu-tion and the side effects at cardiac, hepatic and renal level. Discussions: The group of young experimental animals developed more extensive inflammatory phenomena compared to the group of adult animals. Leflunomide did not significantly improve the evolution and resolu-tion of inflammatory phenomena in either group. Conclusions: We showed for the first time in the world the effects of Leflunomide on the heart, with the occur-rence of myocardial necrosis ( myocardial infarction) as its main adverse effect.

First Report of 'Candidatus Phytoplasma australasiaticum' Associated with Phyllody, Virescence, and Witches'-Broom Disease in Chrysanthemum morifolium in Taiwan.

Chrysanthemum morifolium (Asteraceae) is commonly grown as commercial cut flowers or pot mums worldwide. Common diseases of chrysanthemum include bacterial blight, fungal diseases, viruses, and phytoplasmas (Verma et al. 2003; Taloh et al. 2020). In June 2022, C. morifolium plants showing virescence, stunting, witches' broom, and phyllody symptoms were observed in 10 plants representing 10% of the estimated 100 plants in a field in Taichung City, Taiwan (Fig. S1). Three symptomatic samples along with three asymptomatic ones were collected for further study. Nested PCR was performed with two primer sets, P1/P7 (Deng and Hiruki 1991; Schneider et al. 1995) and R16F2n/R16R2 (Gundersen and Lee 1996) to amplify nearly full-length of 16S rDNA from the collected samples. The target 1.2-kb DNA band was only amplified from the symptomatic chrysanthemum plants. The amplicons were sequenced and a representative sequence deposited in GenBank under accession number OR501416. This sequence was used to search GenBank database by the Basic Local Alignment Search Tool (BLAST) program through the web service of National Center for Biotechnology Information (NCBI). In the 16S rDNA analyses, the three randomly picked amplicons from chrysanthemum phyllody phytoplasma (CPP) shared 100% identity with one another, and all shared 99.5% identity with the, 'Candidatus Phytoplasma australasiae' reference phytoplasma strain (Y10097). Further analysis using iPhyClassifier (Wei et al. 2007) revealed that CPP was most similar to the pattern of the peanut witches' broom phytoplasma in the 16SrII-A subgroup (GenBank Acc. No. L33765), with a pattern similarity coefficient of 1.0. For confirmation, the secY gene was amplified by secY-F/R primers (Li et al. 2014), the 1.2-kb band was sequenced and deposit in GenBank (Acc. No. OR508986). BLAST analysis showed that the secY sequence of CPP shared 99.93% of sequence identities to several 'Ca. P. australasiaticum' strains (MN543069, CP097312, CP120449, KC953013, MW085916, MW070030, CP040925). The phylogenetic tree analysis based on the secY gene by MEGA11 employing maximum-likelihood algorithm was performed and the bootstrap value was set as 1000 times for support of the stability for the clades. The result showed that CPP is closely related to other strains in 16SrII group (Fig. S2). Taken together, CPP is a 'Ca. P. australasiaticum' related-strain in 16SrII-A subgroup. This is the first report of chrysanthemum as a host of this phytoplasma in Taiwan, and might have an impact to the horticultural industry and the growers.

Fibronectin binds integrin α5β1 to regulate macular neovascularization through the Wnt/β-catenin signaling pathway

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the macula. The formation of macular neovascularization (MNV) and subretinal fibrosis of AMD is the most classic cause of the loss of vision in older adults worldwide. While the underlying causes of MNV and subretinal fibrosis remain elusive, the common feature of many common retinal diseases is changes the proportions of protein deposition in extracellular matrix (ECM) when compared to normal tissue. In ECM, fibronectin (FN) is a crucial component and plays a pivotal part not only in fibrotic diseases but also in the process of angiogenesis. The study aims to understand the role of ligand FN and its common integrin receptor α5β1 on MNV, and to understand the molecular mechanism involved. To study this, the laser-induced MNV mouse model and the rhesus macaque choroid-retinal endothelial cell line (RF/6A) chemical hypoxia mode were established, and the FN-α5β1 expression levels were detected by immunohistochemistry (IHC) and quantitative real-time PCR analysis (qRT-PCR). Fibronectin expression was silenced using small interfering RNA (siRNA) targeting FN. The tube formation and vitro scratch assays were used to assess the ability to form blood vessels and cell migration. To measure the formation of MNV, immunofluorescence, and Western blot assays were used. These results revealed that the expressions of FN and integrin α5β1 were distinctly increased in the laser-induced MNV mouse model and in the RF/6A cytochemically induced hypoxia model, and the expression tendency was identical. After the use of FN siRNA, the tube formation and migration abilities of the RF/6A cells were lower, the ability of endothelial cells to proliferate was confined and the scope of damage caused by the laser in animal models was significantly cut down. In addition, FN gene knockdown dramatically inhibited the expression of Wnt/β-catenin signal. The interaction of FN with the integrin receptor α5β1 in the constructed model, which may act through the Wnt/β-catenin signaling pathway, was confirmed in this study. In conclusion, FN may be a potential new molecular target for the prevention and treatment of subretinal fibrosis and MNV.

Fungal and Fungal-like Diseases of Halophytes in the Mediterranean Basin: A State-of-the-Art Review

Halophytes are salt-tolerant plants growing in saline ecosystems and are spread throughout the Mediterranean area. Recently, there has been a renewed interest in agricultural exploitation of halophytes, but poor attention has been given to pest and disease management of these species. The objective of this review is to assess the extent and distribution of pathogenic fungal and fungal-like (Oomycota) organisms on major Mediterranean halophytes. We retrieved 92 references spanning over 100 years, with more than half published since 2000. Ascomycota is the best-represented phylum, and the order Pleosporales has the highest species diversity. The order Pucciniales prevails in Basidiomycota, whereas Peronosporales is the richest order within Oomycota. Most of the pathogenic species have been isolated from aboveground organs, especially from leaves. Portulaca oleracea is the species with the most associated pathogens (16) and records (28). Leveillula powdery mildew, caused by Leveillula taurica, is the most common disease among the selected species. Cakile maritima was found to be vulnerable to different mycotoxigenic Alternaria species. Strengthening the research on diseases of halophytes is essential to successfully grow these species and to evaluate the risks related to the presence of mycotoxigenic species, which is crucial for the effective exploitation of halophytes as crops.

Abstract 2021: The RXR agonist MSU-42011 and the MEK inhibitor selumetinib reduce pERK levels in NF1-deficient cells and inhibit cytokine production in macrophages

Abstract Neurofibromatosis type 1 (NF1) is a common genetic disease that predisposes approximately 50% of affected individuals to develop plexiform neurofibromas (PNFs), which can progress to highly aggressive malignant peripheral nerve sheath tumors (MPNSTs) in approximately 10% of patients. NF1 is caused by mutations in the tumor suppressor gene NF1, which encodes for neurofibromin, a negative regulator of RAS activity. Selumetinib, a specific inhibitor of MEK1/2, is the only FDA-approved drug for NF1-associated PNFs. However, the anti-tumor effects of selumetinib are limited in MPNSTs and have dose-limiting side effects. Deficiency of the NF1 gene not only promotes tumorigenesis but also has broad effects on the immune cells and cytokine signaling driven by hyperactive RAS signaling. Because macrophages account for almost half of cells in NF1 lesions and their infiltration correlates with disease progression, we hypothesized that targeting tumor-promoting immune cells could be an alternative approach for treating NF1. The novel retinoid X receptor (RXR) agonist MSU-42011 reduces tumor growth in experimental Kras-driven cancers by decreasing pERK expression, reducing tumor-promoting immune cells like CD206+ macrophages and regulatory T cells, and increasing activated cytotoxic T cells. Here, we treated NF1-deficient cells and macrophages with MSU-42011 and selumetinib, either alone or in combination, using monoculture and conditioned media (CM) conditions. In human PNF cells and mouse MPNSTs, treatment with 200 nM MSU-40211 or 50 nM selumetinib for 3 hours reduced pERK protein levels compared with untreated controls, and the combination treatment enhanced this reduction in pERK protein levels. Additionally, there was a trend toward reduction in cell viability with increasing drug concentrations after 72 hours of the combination treatment. Moreover, CM from human and mouse PNF cells increased the mRNA expression of monocyte chemoattractant CCL2 (C-C motif chemokine ligand 2) and the secretion of IL-6 and TNFα in human THP1 monocytes/macrophages and bone marrow derived macrophages (BMDM). Notably, MSU-42011 and selumetinib alone inhibited CCL2 mRNA expression in THP1 macrophages and BMDM stimulated with CM from human and mouse PNF cells, respectively, and the inhibition of CCL2 mRNA expression was greatest with combination treatment. The combination of MSU42011 and selumetinib also significantly reduced tumor burden in a LL2 model of lung cancer driven by an activating Kras mutation. Based on the similarities in RAS activation and immune cell infiltration in NF1 and lung cancer, our next step is to confirm the immunomodulatory and anti-tumor effects of MSU-42011 and selumetinib in a syngeneic model of PNF and MPNST. Citation Format: Pei-Yu Hung, Jessica A. Moerland, Karen T. Liby. The RXR agonist MSU-42011 and the MEK inhibitor selumetinib reduce pERK levels in NF1-deficient cells and inhibit cytokine production in macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2021.

Neuroprotective effects of the salidroside derivative SHPL-49 via the BDNF/TrkB/Gap43 pathway in rats with cerebral ischemia

Ischemic stroke is a common intravascular disease and one of the leading causes of death and disability. The salidroside derivative SHPL-49, which we previously synthesized, significantly attenuates cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion. To explore the neuroprotective mechanism of SHPL-49, the effects of SHPL-49 on the expression levels of neurotrophic factors in neurons and microglia and the polarization of microglia were investigated in the present study. SHPL-49 activated the brain-derived neurotrophic factor (BDNF) pathway, decreased the number of degenerated neurons, and accelerated neurogenesis in rats with cerebral ischemia. In addition, SHPL-49 promoted the polarization of microglia toward the M2 phenotype to alleviate neuroinflammation. In BV2 cells, SHPL-49 upregulated CD206 mRNA and protein levels and inhibited CD86 mRNA and protein levels. SHPL-49 also increased neurotrophic factor secretion in BV2 cells, which indirectly promoted the survival of primary neurons after oxygen-glucose deprivation (OGD). Proteomics analysis revealed that SHPL-49 promoted growth-associated protein 43 (Gap43) expression. SHPL-49 enhanced synaptic plasticity and increased Gap43 protein levels via activation of the BDNF pathway in the OGD primary neuron model. These results indicate that SHPL-49 prevents cerebral ischemic injury by activating neurotrophic factor pathways and altering microglial polarization. Thus, SHPL-49 is a potential neuroprotective agent.

Native nephrectomy in polycystic kidney disease patients on transplant lists: how and when?

Autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney disease, accounts for approximately 10% of the patients on kidney transplantation waitlists.High rates of complications including hemorrhage, infections, nephrolithiasis and kidney size-related compressive complaints have been reported among ADPKD patients. Therefore, the need for routine native nephrectomy and timing of such procedure in ADPKD patients being prepared for transplantation are debated. Even though pre-transplant nephrectomy has the potential to provide fewer infectious complications due to lack of immunosuppressive medication use, such procedure has been associated with longer hospital stay, loss of residual kidney function and need for dialysis. Although simultaneous nephrectomy and transplantation could potentially lead to longer perioperative duration, perioperative complications and need for blood transfusions, this was not confirmed in cohort studies. Therefore, some institutions routinely perform simultaneous unilateral nephrectomy and kidney transplantation. In this narrative review, our aim is to evaluate the current evidence regarding the need andtiming of nephrectomy in ADPKD patients in relation to kidney transplantation.

Effectiveness of a Self-efficacy Enhanced Program Using Cartoon Animation for Self-care Behaviors Among Schoolchildren with Epilepsy: A Quasi-experimental Study

Epilepsy is one of the most common chronic neurological diseases in children and may cause repeated seizures and complications. Thus, self-care behavior is vital for effective seizure control. This quasi-experimental study examined the effectiveness of the Self-efficacy Enhanced Program Using Cartoon Animation for self-care behaviors among school children with epilepsy. The study was conducted at a pediatric neurological clinic in the outpatient department of a tertiary hospital in Bangkok, Thailand. There were 42 children with epilepsy, aged 10 to 12 years, who participated in the study: 21 in the experiment group and 21 in the control group. The experimental group received the program, which used two cartoon animation videos to enhance self-care behaviors for eight weeks, while the control group received regular care only. The data were collected using demographic and self-care behavior questionnaires and were analyzed using chi-square and t-tests.The results demonstrated that after program completion, the mean scores of total self-care behavior and subscale on medication taking, avoiding triggers seizures, and self-care of abnormal symptoms and seeking information in the experimental group were significantly higher than before receiving it and higher than those in the control group significantly. Nurses should use this program to increase self-care behaviors among children with epilepsy. However, testing the program in other settings with long-term follow-up is needed before it can be used widely.

Study of thyroid disorders in pregnancy and their effects on feto-maternal outcomes

The second most common endocrine disease that occurs during pregnancy is thyroid disease. Overt and subclinical thyroid dysfunction can lead to adverse effects on both the fetus and the mother. Thyroid diseases during pregnancy affect maternal outcomes and neuropsychological development of the fetus. The objectives of this study were to investigate the effects of thyroid disorders on maternal health and its maternal and perinatal outcomes and to formulate a plan for the management of thyroid disorders in pregnancy. This prospective observational study involved 165 pregnant women. They will be assessed using thyroid function tests, and patients with deranged thyroid function will be treated and followed up. Pregnancy and outcomes were recorded. The findings of this research will offer important new information regarding possible side effects linked to thyroid issues in mothers as well as the clear advantages of therapy. Maternal thyroid diseases have several risk factors in addition to clear advantages of treatment.

Naujųjų anti-CD20 monokloninių antikūnų vaidmuo gydant itin aktyvią recidyvuojančiąją remituojančiąją išsėtinę sklerozę: ofatumumabo klinikinis efektyvumas ir saugumas

Multiple sclerosis is the most common chronic demyelinating neurodegenerative central nervous system disease among young adults. Considering its extent in a relatively young population, multiple sclerosis determines a significant socioeconomic burden to the society due to the cost of disease modifying treatment and a lower working capacity of patients and their caregivers. It is important to control neuroinflammation in the central nervous system caused by the pathologic activity of immune cells by considering a high efficacy treatment early in the disease course in order to prevent accumulation of neurological damage and to improve long term outcomes. According to the newest clinical studies, anti-CD20 therapies have proven their effectiveness and safety in active relapsing multiple sclerosis treatment: since 2018, ocrelizumab, and, since 2023, ofatumumab have both been available as treatment options in Lithuania. Because of its high potency and safety, as well as the specific mechanism of action, ofatumumab is effective in lower doses, and, after initial training at a health care facility, it can be self-administered through subcutaneous injection. This article reviews the efficacy, safety data and treatment indications of the latest available anti-CD20 monoclonal antibodies.