Antibody-secreting cells as a source of NR1-IgGs in N-methyl-D-aspartate receptor-antibody encephalitis.

BACKGROUND: The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is known, but the immunobiological mechanisms underlying their production remain unclear. METHODS: For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum NR1-IgGs levels. Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro. RESULTS: For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pre-germinal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs. CONCLUSIONS: These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis.

The role of proinflammatory cytokines and CXC chemokines (CXCL1-CXCL16) in the progression of prostate cancer: insights on their therapeutic management.

Reproductive cancers are malignancies that develop in the reproductive organs. One of the leading cancers affecting the male reproductive system on a global scale is prostate cancer (PCa). The negative consequences of PCa metastases endure and are severe, significantly affecting mortality and life quality for those who are affected. The association between inflammation and PCa has captured interest for a while. Inflammatory cells, cytokines, CXC chemokines, signaling pathways, and other elements make up the tumor microenvironment (TME), which is characterized by inflammation. Inflammatory cytokines and CXC chemokines are especially crucial for PCa development and prognosis. Cytokines (interleukins) and CXC chemokines such as IL-1, IL-6, IL-7, IL-17, TGF-ß, TNF-α, CXCL1-CXCL6, and CXCL8-CXCL16 are thought to be responsible for the pleiotropic effects of PCa, which include inflammation, progression, angiogenesis, leukocyte infiltration in advanced PCa, and therapeutic resistance. The inflammatory cytokine and CXC chemokines systems are also promising candidates for PCa suppression and immunotherapy. Therefore, the purpose of this work is to provide insight on how the spectra of inflammatory cytokines and CXC chemokines evolve as PCa develops and spreads. We also discussed recent developments in our awareness of the diverse molecular signaling pathways of these circulating cytokines and CXC chemokines, as well as their associated receptors, which may one day serve as PCa-targeted therapies. Moreover, the current status and potential of theranostic PCa therapies based on cytokines, CXC chemokines, and CXC receptors (CXCRs) are examined.

The efficacy of repetitive transcranial magnetic stimulation for Parkinson disease patients with depression.

Objective: To evaluate the efficacy of repetitive transcranial magnetic stimulation for Parkinson disease (PD) patients with depression.Methods: A meta-analysis was performed using relevant randomized controlled trials (RCTs) from online databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. Studies were selected according to pre-defined inclusion and exclusion criteria, and the quality of the studies was evaluated using the Jadad Scale. All data were pooled by RevMan 5.2 software for meta-analysis.Results: The review covered 528 articles, and 7 articles with Jadad score ≥4 were included in the analysis. The meta-analysis showed that, compared to sham repetitive transcranial magnetic stimulation (sham-rTMS), repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex (DLPFC) improved depression, but that there was no significant difference in depression improvement between rTMS and selective serotonin reuptake inhibitor (SSRI) treatment. In contrast, rTMS over DLPFC did not improve motor function compared to sham-rTMS or SSRI, and the studies that included neurocognitive measures showed no significant difference between rTMS and sham-rTMS.Conclusion: This meta-analysis provides evidence that rTMS over DLPFC can improve depression similar to SSRI treatment, has no effect on the motor function and cognition of PD patients with depression.

Mesencephalic astrocyte-derived neurotrophic factor and its role in nervous system disease.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a member of the novel evolutionary conserved neurotrophic factor (NTF) family. MANF has a unique structure and an unparalleled dual mode of action that differs from other known NTFs. Recent studies have shown that MANF protects cells from endoplasmic reticulum stress. In addition, an increasing number of studies have found MANF plays an important role in nervous system disease. This review focuses on MANF, summarizing its unique structure, potential signaling pathway, and role in neurological disease.

Correlation between SUA and prognosis in CHF patients after revascularization.

Background: To explore the correlation between serum uric acid (SUA) and prognosis in patients with chronic heart failure (CHF) after revascularization. Methods: A total of 126 patients with CHF undergoing revascularization [coronary artery intervention (PCI) or coronary artery bypass grafting (CABG)] in the hospital were enrolled as CHF group between December 2021 and October 2022, while 126 healthy controls during the same period were enrolled as healthy control group. The levels of SUA, inflammatory factors and cardiac function in the two groups were detected. The correlation between SUA level and inflammatory factors, cardiac function levels was analyzed. All patients in CHF group were followed up for 6 months to observe prognosis. The differences in the above indexes among patients with different prognosis were compared. The risk factors of prognosis were analyzed by multivariate Logistic regression analysis, and their predictive value for prognosis was evaluated by ROC curves analysis.

Influence of Reinforcement Architecture on Behavior of Flax/PLA Green Composites under Low-Velocity Impact.

The main goal of this study is the comparison of different reinforcement architectures on the low-velocity impact behavior of green composites. The study includes the comparison of unidirectional, basket weave, and twill weave flax/PLA composites, they are subjected to unidirectional tensile tests, drop-weight impact tests, and after-impact compression tests. Results show that the unidirectional composite demonstrates superior tensile strength and initial modulus due to reduced fiber crimp, while basket weave exhibits the highest energy absorption capability and strain capacity attributed to its higher fiber-weight ratio and fiber crimp. Unidirectional composite also shows a larger impacted damage area compared to basket weave and twill weave, attributed to its internal architecture. Residual compressive strength across all composites decreased by 40% compared to the reference sample. However, the reduction in stiffness after impact was different, UD/PLA composite stiffness was reduced by 30% while the reduction in BW/PLA and T/PLA composites was about 20%.

On the Numerical Modeling of Flax/PLA Bumper Beams.

Significant progress has been made in green composites developing fully biodegradable composites made of microbially degradable polymers reinforced with natural fibers. However, an improvement in the development of numerical models to predict the damage of green composites is necessary to extend their use in industrial applications of structural responsibility. This paper is focused on developing a numerical model that can predict the failure modes of four types of bumper beams made of flax/PLA green composites with different cross sections. The predictions regarding energy absorption, contact force history, and extension of delamination were compared with experimental results to validate the FEM model, and both results revealed a good agreement. Finally, the FEM model was used to analyze the failure modes of the bumper beams as a function of the impact energy and cross-section roundness. The impact energy threshold defined as the maximum absorbed-energy capability of the beam match with the impact energy that produces delaminations extended through all the cross sections. Experimental and numerical results revealed that the threshold energy, where the maximum energy-absorption capability is reached, for Type A is over 60 J; for Type B and C is around 60 J; and for Type D is at 50 J. Since delamination is concentrated at the cross-section corners, the threshold energy decreases with the cross-section roundness because the higher the roundness ratio, the wider the delamination extension.

Prediction of Critical Buckling Load on Open Cross-Section Columns of Flax/PLA Green Composites.

The present work aims to analyze the buckling behavior of nonlinear elastic columns with different open cross-sections and slenderness ratios to verify the limits of the modified Ludwick law to predict the critical buckling load. The results of the analytical formulation based on the modified Ludwick law are compared with a FEM numerical model using the Marlow hyperelastic behavior and experimental results conducted on flax/PLA specimens with three different open cross-sections. The comparative results show that the numerical predictions agree with the experimental results in all the cases. The FEM model can exactly reproduce the buckling behavior of the C-section columns. However, the prediction errors for the C90 and C180 columns are higher than for the C60 columns. Moreover, the theoretical estimations indicate that the C90 cross-section column is the limit of application of the modified Ludwick law to predict the critical buckling load of nonlinear elastic columns with open cross-sections, and the C180 column is out of the prediction limits. Generally, the numerical and theoretical models underestimated the scattering effects of the predictions because more experimental variables were not considered by the models.

Use of Artificial Neural Networks to Optimize Stacking Sequence in UHMWPE Protections.

The aim of the present work is to provide a methodology to evaluate the influence of stacking sequence on the ballistic performance of ultra-high molecular weight polyethylene (UHMWPE) protections. The proposed methodology is based on the combination of experimental tests, numerical modelling, and Artificial Neural Networks (ANN). High-velocity impact experimental tests were conducted to validate the numerical model. The validated Finite Element Method (FEM) model was used to provide data to train and to validate the ANN. Finally, the ANN was used to find the best stacking sequence combining layers of three UHMWPE materials with different qualities. The results showed that the three UHMWPE materials can be properly combined to provide a solution with a better ballistic performance than using only the material with highest quality. These results imply that costs can be reduced increasing the ballistic limit of the UHMWPE protections. When the weight ratios of the three materials remain constant, the optimal results occur when the highest-performance material is placed in the back face. Furthermore, ANN simulation showed that the optimal results occur when the weight ratio of the highest-performance material is 79.2%.

MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength.

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSCScx) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSCScx derived exosomes (BMMSCScx-exos). Local injection of BMMSCScx-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSCScx-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.

Method for Ferrite Nanomaterials-Mediated Cellular Magnetic Hyperthermia.

Magnetic hyperthermia (MH) mediated by magnetic nanoparticles is one of the most promising antitumor modalities. The past several decades have witnessed great progress for MH antitumor therapy in scientific trials and clinic applications since it was initially advanced by Gilchrist et al. The ultimate object of MH in vivo is to efficiently kill cancer cells, and hence, it is of great importance to develop an optimized cellular MH method to evaluate the therapeutic efficiency in vitro. In this study, we systematically studied the considerable affecting factors of cancer cell-killing efficiency during the cellular MH process, including the region of cell vessel positioned inside the alternating magnetic field copper coil, the magnetic field amplitude, the types of cancer cells, etc. Taking all these into account, we introduced a method for standardizing the cellular MH process to evaluate the cell-killing efficiency.

Refinement and Evaluation of a Chinese and Western Medication Adherence Scale for Patients with Chronic Kidney Disease: Item Response Theory Analyses.

PURPOSE: This study aimed to simplify the version-1 Chinese and Western medication adherence scale for patients with chronic kidney disease (CKD) to a version-2 scale using item response theory (IRT) analyses, and to further evaluate the performance of the version-2 scale. MATERIALS AND METHODS: Firstly, we refined the version-1 scale using IRT analyses to examine the discrimination parameter (a), difficulty parameter (b) and maximum information function peak (Imax). The final scale refinement from version-1 to version-2 scale was also decided upon clinical considerations. Secondly, we analyzed the reliability and validity of version-2 scale using classical test theory (CTT), as well as difficulty, discrimination and Imax of version-1 and version-2 scale using IRT in order to conduct scale evaluation. RESULTS: For scale refinement, the 26-item version-1 scale was reduced to a 15-item version-2 scale after IRT analyses. For scale evaluation using CTT, internal consistency reliability (total Cronbach α = 0.842) and test-rest reliability (r = 0.909) of version-2 scale were desirable. Content validity indicated 3 components of knowledge, belief and behaviors. We found meritorious construct validity with 3 detected components as the same construct of medication knowledge (items 1-9), medication behavior (items 13-15), and medication belief (items 10-12) based upon exploratory factor analysis. The correlation between the version-2 scale and Morisky, Green and Levine scale (MGL scale) was weak (Pearson coefficient = 0.349). For scale evaluation with IRT, the findings showed enhanced discrimination and decreased difficulty of most retained items (items 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15), decreased Imax of items 1, 2, 3, 4, 6, 11, 14, as well as increased Imax of items 5, 7, 8, 9, 10, 12, 13, 14, 15 in the version-2 scale than in the version-1 scale. CONCLUSION: The original Chinese and Western medication adherence scale was refined to a 15-item version-2 scale after IRT analyses. The scale evaluation using CTT and IRT showed the version-2 scale had the desirable reliability, validity, discrimination, difficulty, and information providedoverall. Therefore, the version-2 scale is clinically feasible to assess the medication adherence of CKD patients.

Risk factors for drug-resistant epilepsy: A systematic review and meta-analysis.

BACKGROUND: Drug resistant epilepsy (DRE) is very common among children and adults and studies had found some related risk factors for DRE, while the results were not consistent. The aim of this study was to identify risk factors for drug-resistant epilepsy. METHODS: Three electronic databases (Medline, Embase and Cochrane library) were searched to identify studies with a cohort design reporting on epidemiologic evidence regarding risk factors for DRE. RESULTS: The pooled prevalence of DRE in newly diagnosed epilepsy patients was 25% (95% CI 17-32%). Abnormal electroencephalography (EEG) (both slow wave and epileptiform discharges) (RR 2.80; 95% CI 1.95-4.0), status epilepticus (SE) (RR 11.60; 95% CI 7.39-18.22), symptomatic etiology (RR 3.36; 95% CI 2.53-4.46), multiple seizure types (RR 3.66; 95% CI 2.37-5.64) and febrile seizures (RR 3.43; 95% CI 1.95-6.02) were identified as strong risk factors for DRE. In addition, firm conclusions cannot be drawn for poor short-term outcomes of therapy, neurodevelopment delay and high initial seizure frequency for the heterogeneity of study results. The predictive effect of focus onset seizure was not stable after removing one study and switching the effect model. Age of onset was not risk factors for DRE. CONCLUSIONS: The current meta-analysis identified potential risk factors for DRE. The results may contribute to better prevention strategies and treatments for DRE.

Indirect comparison of third-generation antiepileptic drugs as adjunctive treatment for uncontrolled focal epilepsy.

PURPOSE: Eslicarbazepine (ESL), Lacosamide (LAC), Perampanel (PER) and Brivaracetam (BRV), have recently been marketed as third-generation antiepileptic drugs (AEDs). We conducted a meta-analysis to indirectly compare overall efficacy and tolerability between third-generation AEDs in uncontrolled focal epilepsy. METHODS: We performed an online database search using Pubmed, Embase, Cochrane Online Library, and Clinicaltrial.gov for all available randomized controlled trials (RCTs) that investigated the therapeutic effects over a range of AED doses versus placebo. We then compared clinical efficacy and tolerability between these newer AEDs using Indirect Treatment Comparison software. RESULTS: Nineteen RCTs with a total of 7245 patients were included in our study. There were no significant differences in the risk difference of 50% responder rates and seizure free rates between third generation AEDs, regardless of dose. The risk of treatment emergent adverse events was significantly higher with ESL and PER treatment compared to BRV at all doses combined. Withdrawal rates due to adverse events were also significantly higher in patients treated with the highest doses of LAC and PER versus BRV, while treatment with ESL or LAC was related to higher withdrawal rates versus BRV when all doses were combined. CONCLUSIONS: Our analysis suggested there were no significant differences in efficacy between third generation AEDs in uncontrolled focal epilepsy. BRV may have the best tolerability profile. The other AEDs were associated with a higher risk for intolerable adverse, especially when taken at a high doses. The results from these indirect comparisons warrant further examination and verification through future well-designed trials.

Three-week topical treatment with placenta-derived mesenchymal stem cells hydrogel in a patient with diabetic foot ulcer: A case report.

RATIONALE: Diabetic foot ulcer (DFU) is a chronic complication of diabetes characterized by continuity, repeatability, and nonhealing. In recent years, mesenchymal stem cells hydrogel complex has been a new emerging technique in the treatment of DFU. The placenta-derived mesenchymal stem cells (PDMSCs) hydrogel is multipotent, and can secrete growth factors, cytokines, and immunomodulatory substances which could accelerate wound healing. PATIENT CONCERNS: In this case report, we present a 57-year-old female with type 2 diabetes mellitus and a 20-day DFU.A wound bed located at the dorsalis pedis of the right foot, and conventional therapies had no effect on the foot. DIAGNOSES: The patient was confirmed a diagnosis of type 2 DM with diabetic foot (Wagner classification III). INTERVENTIONS: To assess the efficacy and safety of PDMSCs hydrogel in wound repair and to improve the rate of wound healing, we administered PDMSCs hydrogel (cell number: 1 × 10/cells/cm) topically into the wound with the patient's permission. OUTCOMES: The patient's foot ulcer was almost healed, and foot function in walking was well preserved. No complications were observed. No recurrence occurred in the subsequent 6 months. LESSONS: To the best of our knowledge, this is the first patient globally to receive PDMSCs hydrogel to treat DFU. The present case study suggests that PDMSCs hydrogel may provide a new approach to DFU treatment. Clinical Trial Registration-URL: http://www.chictr.org.cn/searchproj.aspx:chiCRT-ONC-16008732.

CHIP involves in non-small cell lung cancer prognosis through VEGF pathway.

AIM: CHIP (c-terminal Hsp70-interacting protein) is an E3 ligase playing vital roles in various cancers. The VEGF pathway has become an important therapeutic target in non-small cell lung cancer (NSCLC). However, little is known about the role of CHIP and the relationship between CHIP and VEGF-VEGFR2 (VEGF receptor 2) pathway in NSCLC. In this study we aimed to investigate the clinical function of CHIP in NSCLC and explore the relevant regulatory mechanism. METHODS: QRT-PCR was performed to detect CHIP expression in NSCLC tissues. The association of CHIP expression and clinical parameters was analyzed using the Chi-square test. Kaplan- Meier and Cox analyses were performed to identify the role of CHIP in the prognosis of NSCLC patients. ELISA test was used to detect the VEGF secretion of NSCLC cells and western blot were used to detected the protein expression of VEGFR2 in NSCLC cells. RESULTS: and the results revealed that CHIP expression was decreased in NSCLC tissues and significantly correlated with clinical stages, lymph node metastasis and distant metastasis (P<0.05). Moreover, Kaplan-Meier and Cox regression analyses showed that patients with negative expression of CHIP had a shorter survival time and CHIP could be an independent prognostic biomarker. In addition, ELISA tests showed that CHIP negatively regulated the secretion level of VEGF. Furthermore, western blot assay indicated that the VEGFR2 protein level was reduced after CHIP over-expression. CONCLUSIONS: Taken together, our findings demonstrate for the first time that CHIP may serve as a promising prognostic biomarker for NSCLC patients and it may be involved in NSCLC angiogenesis through regulating VEGF secretion and expression of VEGFR2.