Na2CO3-responsive mechanism insight from quantitative proteomics and SlRUB gene function in Salix linearistipularis seedlings.

Mongolian willow (Salix linearistipularis) is a naturally occurring woody dioecious plant in the saline soils of north-eastern China, which has a high tolerance to alkaline salts. Although transcriptomics studies have identified a large number of salinity-responsive genes, the mechanism of salt tolerance in Mongolian willow is not clear. Here, we found that in response to Na2CO3 stress, Mongolian willow regulates osmotic homeostasis by accumulating proline and soluble sugars and scavenges reactive oxygen species (ROS) by antioxidant enzymes and non-enzymatic antioxidants. Our quantitative proteomics study identified 154 salt-sensitive proteins mainly involved in maintaining the stability of the photosynthetic system and ROS homeostasis to cope with Na2CO3 stress. Among them, Na2CO3-induced rubredoxin (RUB) was predicted to be associated with 122 proteins for the modulation of these processes. The chloroplast-localized S. linearistipularis rubredoxin (SlRUB) was highly expressed in leaves and was significantly induced under Na2CO3 stress. Phenotypic analysis of overexpression, mutation and complementation materials of RUB in Arabidopsis suggests that SlRUB is critical for the regulation of photosynthesis, ROS scavenging and other metabolisms in the seedlings of Mongolian willow to cope with Na2CO3 stress. This provides more clues to better understand the alkali-responsive mechanism and RUB functions in the woody Mongolian willow.

Efficacy and safety of GLucocorticoid injections into InfrapaTellar faT pad in patients with knee ostEoarthRitiS: protocol for the GLITTERS randomized controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. METHODS: GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher's exact test). DISCUSSION: GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk-benefit profile of this treatment in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT05291650. Registered on 23 March 2022.

Predictive Value of Pretreatment Lymphocyte-to-Monocyte Ratio and Platelet-to-Lymphocyte Ratio in the Survival of Nasopharyngeal Carcinoma Patients.

OBJECTIVE: The present study aimed to investigate the predictive value of some indexes, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory response index (SIRI), and systemic immune-inflammatory index (SII) in the survival of nasopharyngeal carcinoma (NPC) and provide reference for the treatment. METHODS: A retrospective analysis was performed on 216 patients from 2016 to 2018. The cutoff values of these indexes were determined by the receiver operating characteristic (ROC) curve. The prognostic value of the indexes was evaluated according to the rate of overall survival (OS), regional recurrence-free survival (RRFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS). RESULTS: The survival analysis showed that NLR ≤2.695 (P = 0.017) and PLR ≤140.065 (P = 0.041) were associated with poor OS; however, the LMR and SIRI showed no significant statistical significance. NLR ≤2.045 (P = 0.018) and PLR ≤125.605 (P = 0.003) were associated with poor RRFS, LMR ≤2.535 (P = 0.027) and PLR ≤140.065 (P = 0.009) were associated with poor DMFS, NLR ≤2.125 (P = 0.018) and PLR ≤132.645 (P = 0.026) were associated with poor LRRFS, respectively. Logistic regression analysis showed that low LMR (≤2.535) was significantly inferior in OS (HR 23.085, 95% CI 3.425-155.622, P = 0.001) and DMFS (HR 22.839, 95% CI 4.096-127.343, P < 0.001). Moreover, low PLR (≤140.065) remained significantly related to worse OS (HR 11.908, 95% CI 1.295-109.517, P = 0.029) and DMFS (HR 9.556, 95% CI 1.448-63.088, P = 0.019). CONCLUSION: The index LMR and PLR can be used for predicting survival in NPC patients.

Protection of Ficus pandurata Hance against acute alcohol-induced liver damage in mice via suppressing oxidative stress, inflammation, and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus pandurata Hance (FPH) is a traditional Chinese herbal medicine, which is commonly used for liver protection in the folk of Southeast China. However, the medicinal part and pharmacological mechanism have not been clarified yet. AIM OF THE STUDY: This study aims to investigate the medicinal part of FPH for liver protection and uncover the potential mechanism. MATERIALS AND METHODS: Acute alcoholic liver damage (ALD) mice model induced by intragastric administration with 50% alcohol was used to evaluate the liver protection of FPH. Different parts of FPH, including the root (FPHR), stem (FPHS), leaf (FPHL), and whole plant (FPHWP), were selected to investigate the liver-protected efficacy and determine which part is the medicinal part. Acute oral toxicity (AOT) test was performed to determine the acute toxicity of FPH on Kunming mice. The liver-protected effect of FPH was determined by evaluating the liver function, liver morphological changes, and liver pathological changes. The underlying mechanism was investigated by evaluating the effect on oxidative stress, inflammation, and apoptosis in liver tissues via ELISA, H&E staining, Western Blot, and TUNEL staining assays. RESULTS: In the screening test for medicinal parts of FPH, all of the extracts from FPHR, FPHS, FPHL, and FPHWP could alleviate the acute ALD of mice, including reducing abnormal levels of AST, ALT, and relative liver weight. Especially, the alleviated efficacies of FPHS and FPHL were better than those of FPHWP and FPHR, showing that the aerial part (FPHAP, including the stem and leaf), is probably the medicinal part of FPH against acute ALD. In the AOT test, FPHAP at the maximum administration dosage (480 g/kg, calculated based on the quantity of crude material) did not induce obvious abnormality and death of mice, and had no significant influence on body weight, as well as the relative organ weight, showing that the maximum tolerated dose (MTD) of FPHAP was 480 g/kg on Kunming mice. In the anti-acute ALD study, FPHAP significantly reduced the levels of AST, ALT, LDH, ROS, MDA, TNF-α, IL-1ß, IL-18, and IL-6, alleviated the morphology of liver injury, increased the levels of SOD and GSH, up-regulated the expressions of Nrf-2, HO-1 and NQO1, and reduced apoptosis of liver cells in acute ALD mice, indicating that FPHAP could significantly alleviate acute ALD by suppressing oxidative stress, inflammation, and apoptosis. CONCLUSIONS: FPH could protect acute alcohol-induced liver damage of mice by suppressing oxidative stress, inflammation, and apoptosis. Our study provides scientific evidence for the therapeutic effect of Ficus pandurata Hance in acute ALD mice and suggests its potential development in humans for liver protection, supporting its traditional application.

Involuntary, forced or voluntary exercise can ameliorate the cognitive deficits by enhancing levels of hippocampal NMDAR1, pAMPAR1 and pCaMKII in a model of vascular dementia.

Objectives: To investigate the effect on vascular dementia of involuntary exercise induced by functional electrical stimulation and of forced and voluntary exercise, focusing on the recovery of cognitive function and using a rat model of dementia.Methods: A demential model was created in Wistar rats who were then given forced exercise, allowed voluntary exercise (wheel running) or had exercise induced through functional electrical stimulation. Their responses were quantified using a Morris water maze and by measuring long-term potentiation in the hippocampus. Immunohistochemical staining was used to evaluate neurogenesis in the hippocampus and Nissl staining was applied to visualize viable neuron loss in the DG sector. In addition, the levels of NMDAR1, AMPAR1, pAMPAR1, pCaMKII, CaMKII, Bcl-2 and Bax in the hippocampus were assessed by western blotting.Results: All of the exercise groups showed a recovery of cognitive performance and improved long-term potentiation. The three modes of exercise all increased the number of DCX immunopositive cells and reduced losses of intact-appearing neurons in the hippocampal DG zones roughly equally. All proved about equally effective in increasing the levels of NMDAR1, pAMPAR1 and pCaMKII and increasing the Bcl-2/Bax ratio to protect neurons from apoptosis.Conclusion: Exercise induced by electrical stimulation has beneficial effects comparable to those of other types of exercise for alleviating the cognitive deficits of vascular dementia.

Interleukin-33 deficiency exacerbated experimental autoimmune encephalomyelitis with an influence on immune cells and glia cells.

Interleukin (IL)-33, a member of the IL-1 cytokine family, is highly expressed in central nervous system (CNS), suggesting its potential role in CNS. Although some studies have focused on the role of IL-33 in multiple sclerosis (MS) / experimental autoimmune encephalomyelitis (EAE), an autoimmune disease characterized by demyelination and axonal damage in CNS, the exact role of IL-33 in MS/EAE remains unclear and controversial. Here, we used IL-33 knockout mice to clarify the role of endogenous IL-33 in EAE by simultaneously eliminating its role as a nuclear transcription factor and an extracellular cytokine. We found that the clinical score in IL-33 knockout EAE mice was higher accompanied by more severe demyelination compared with the wild-type (WT) EAE mice. As for the main immune cells participating in EAE in IL-33 knockout mice, pathogenic effector T cells increased both in peripheral immune organs and CNS, while CD4+FOXP3+ regulatory T cells decreased in spleen and lymph nodes, Th2 cells and natural killer (NK) cells decreased in CNS. Additionally, the populations of microglia/macrophages and CD11C+CD11B+ dendritic cells (DCs) increased in CNS of IL-33 knockout mice with EAE, among which iNOS-producing microglia/macrophages increased. Moreover, resident astrocytes/microglia were more activated in IL-33 knockout mice with EAE. In vitro, after blocking the IL-33, the proliferation of primary astrocytes, the production of MCP-1/CCL2 and TNF-α by astrocytes, and the production of TNF-α by primary microglia stimulated by the homogenate of the peak stage of EAE were increased. Our results indicate that IL-33 plays a protective role in EAE and exerts extensive influences on multiple immune cells and neural cells involved in EAE.

A longitudinal study on the radiation-induced thyroid gland changes after external beam radiotherapy of nasopharyngeal carcinoma.

BACKGROUND: Radiation-induced thyroid disorders have been reported in radiotherapy of head and neck cancers. This study evaluated the radiation-induced damages to thyroid gland in patients with nasopharyngeal carcinoma (NPC). METHODS: Forty-five patients with NPC treated by radiotherapy underwent baseline thyroid hormones (free triiodothyronine, free thyroxine [fT4], and thyrotropin [TSH]) examination and CT scan before radiotherapy. The volume of the thyroid gland was calculated by delineating the structure in the corresponding CT slices using the radiotherapy treatment planning system. The thyroid doses were estimated using the treatment planning system. Subsequent CT scans were conducted at 6, 12, and 18 months after radiotherapy, whereas the hormone levels were assessed at 3, 6, 12, and 18 months after radiotherapy. Trend lines of the volume and hormone level changes against time were plotted. The relationship between the dose and the change of thyroid volume and hormone levels were evaluated using the Pearson correlation test. RESULTS: An average of 20% thyroid volume reduction in the first 6 months and a further 8% shrinkage at 12 months after radiotherapy were observed. The volume reduction was dependent on the mean thyroid doses at 6, 12, and 18 months after radiotherapy (r = -0.399, -0.472, and -0.417, respectively). Serum free triiodothyronine and fT4 levels showed mild changes of <2.5% at 6 months, started to drop by 8.8% and 11.3%, respectively, at 12 months, and became stable at 18 months. The mean serum TSH level increased mildly at 6 months after radiotherapy and more steeply after 18 months. At 18 months after radiotherapy, 12 patients had primary hypothyroidism with an elevated serum TSH, in which 4 of them also presented with low serum fT4. There was a significant difference (p = 0.014) in the mean thyroid doses between patients with hypothyroidism and normal thyroid function. CONCLUSIONS: Radiotherapy for patients with NPC caused radiation-induced changes of the thyroid gland. The shrinkage of the gland was greatest in the first 6 months after radiotherapy, whereas the serum fT4 and TSH levels changed at 12 months. Radiation-induced changes were dependent on the mean dose to the gland. Therefore, measures to reduce the thyroid dose in radiotherapy should be considered.

[Application study of the 2008 staging system of nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: The 2008 staging system of nasopharyngeal carcinoma (NPC) was generated based on the NPC 92 and AJCC staging system. It remains open to be consummated. This study was to evaluate its rationality as well as compare the stage distribution among the 3 staging systems, by using of MRI imaging. METHODS: MRI data was collected from a cohort of 177 cases of untreated NPC for retrospective review. We accepted the nasal involvement criteria of 2008 staging system, in which the borderline between the nasal cavity and nasopharynx was a line linked between both posterior walls of the maxillary sinus, for all of the 3 systems. RESULTS: Involvement of oropharynx, nasopharynx, soft palatine, prevertebral muscles, post-styloid space, intracranial, orbit, 1st and/or 2nd cervical body are 100% accompanied with other same or more advanced T-stage classifications. The same situations happened in more than 95% of involvement of the medial pterygoid muscle or masticator space beyond it. Cervical lymph node metastasis (LNM) accounted for 76.3%. Proportion of metastatic lymph node extracapsular extension (ECE) and/or bilateral neck LNM elevated as maximum diameter of the node increased, no matter transverse or longitudinal. There were 11 cases of parotid LNM in this group. Advanced stage accounted for 81.4%, 78.5% and 75.7% in 2008, UICC and NPC 92 staging system, respectively, without statistic difference. CONCLUSION: Nasal involvement criteria and T-stage classification of the medial pterygoid muscle defined by NPC 2008 staging system seems reasonable. Stage distribution is also similar to the other 2 systems. However, diameter of the LNM might not be a prognostic factor. Parameters such as how to classify a parotid LNM, or a node which occupies more than one region, require further clarify.