Emodin alleviates arthritis pain through reducing spinal inflammation and oxidative stress.

Chronic pain is the predominant problem for rheumatoid arthritis patients, and negatively affects quality of life. Arthritis pain management remains largely inadequate, and developing new treatment strategies are urgently needed. Spinal inflammation and oxidative stress contribute to arthritis pain and represent ideal targets for the treatment of arthritis pain. In the present study, collagen-induced arthritis (CIA) mouse model was established by intradermally injection of type II collagen (CII) in complete Freund's adjuvant (CFA) solution, and exhibited as paw and ankle swelling, pain hypersensitivity and motor disability. In spinal cord, CIA inducement triggered spinal inflammatory reaction presenting with inflammatory cells infiltration, increased Interleukin-1ß (IL-1ß) expression, and up-regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase-1 levels, elevated spinal oxidative level presenting as decreased nuclear factor E2-related factor 2 (Nrf2) expression and Superoxide dismutase (SOD) activity. To explore potential therapeutic options for arthritis pain, emodin was intraperitoneally injected for 3 days on CIA mice. Emodin treatment statistically elevated mechanical pain sensitivity, suppressed spontaneous pain, recovered motor coordination, decreased spinal inflammation score and IL-1ß expression, increased spinal Nrf2 expression and SOD activity. Further, AutoDock data showed that emodin bind to Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) through two electrovalent bonds. And emodin treatment increased the phosphorylated AMPK at threonine 172. In summary, emodin treatment activates AMPK, suppresses NLRP3 inflammasome response, elevates antioxidant response, inhibits spinal inflammatory reaction and alleviates arthritis pain.

Turmeric and curcuminiods ameliorate disorders of glycometabolism among subjects with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Metabolic diseases are globally popular, and a systematic review and meta-analysis of turmeric and curcuminoids on glucose metabolism among people with metabolic diseases was performed. DESIGN: We comprehensively searched Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, the Cochrane Library and two Chinese databases, Wanfang and CNKI for RCTs that focused on the effects of turmeric and curcuminoids on fasting blood glucose (FBG), hemoglobin A1C (HbA1c), fasting serum insulin (FSI) and HOMA-IR among patients with metabolic diseases. The FBG and HbA1c were the main outcomes to be analyzed. With random-effects models, separate meta-analyses were conducted by inverse-variance and reported as WMD with 95% CIs. RESULTS: Evidence from 17 RCTs including 22 trials showed that turmeric and curcuminoids lowered FBG by - 7.86 mg/dL (95% CI: -12.04, -3.67 mg/dL; P = 0.0002), HbA1c by - 0.38% (95% CI: -0.52%, -0.23%; P < 0.00001) and HOMA-IR by - 1.01 (95% CI: -1.6, -0.42; P = 0.0008). Moreover, they decreased fasting serum insulin by - 1.69 mU/L (95% CI: -3.22, -0.16 mU/L; P = 0.03) after more than 8 weeks of intervention in a subgroup analysis. CONCLUSIONS: Turmeric and curcuminiods decrease FBG, HbA1c and HOMA-IR significantly among subjects with metabolic disease. Additionally, they may have an effect on FSI concentrations if the intervention period is more than 8 weeks. However, attention should be paid to these outcomes due to the significant heterogeneity.

Prognostic significance of low TSH concentration in patients with COVID-19 presenting with non-thyroidal illness syndrome.

BACKGROUND: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI. METHODS: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality. RESULTS: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003). CONCLUSIONS: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.

Clinical significance of SIRT3 and inflammatory factors in multiple myeloma patients with bortezomib-induced peripheral neuropathy: a cohort study.

The present study aimed to investigate the role of SIRT3 and inflammatory factors in bortezomib-induced peripheral neuropathy (PN). This prospective observational cohort study included a total of 159 patients of multiple myeloma patients during June 2016 to June 2019. All patients received the strategy of bortezomib and dexamethasone and were further divided into the PN group and the non-PN group. Serum SIRT3, CRP, IL-6 and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA). During the study period, 76 (47.8%) patients developed PN. The inflammatory factors all gradually decreased and SIRT3 levels were gradually increased after treatment by bortezomib combined with dexamethasone compared with the baseline. The levels of all inflammatory factors were markedly higher, while SIRT3 levels were lower in PN patients compared with the non-PN patients at the same time point after treatment. In PN grade III patients, the serum levels of CRP, IL-6 and TNF-α were significantly higher, while serum levels of SIRT3 were markedly lower than the grade I-II patients. SIRT3 was negatively correlated with CRP, IL-6 and TNF-α. After nursing treatment and reduction of bortezomib dose, the levels of SIRT3 significantly increased, while levels of inflammatory decreased in PN patients with grade III. SIRT3 and inflammatory factors showed the potential for diagnosis of bortezomib-induced PN. Besides, SIRT3, IL-6 and TNF-α were the independent risk factors for MM patients developing PN after treatment of bortezomib. Higher inflammatory factors and lower SIRT3 might be associated with the development of bortezomib-induced PN in multiple myeloma patients, which might be reversed by decreased bortezomib dose and proper nursing treatment.

Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88.

BACKGROUNDS: Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is not completely clear. METHODS: The inflammatory polarization of Raw264.7 cells and primary peritoneal macrophages were induced by LPS, and then effects and underlying mechanisms of BBR were explored. An inflammatory model was established by LPS treatment at different concentrations for different treatment time. An ELISA assay was used to detect the secretions of TNF-α. RT-PCR was applied to detect M1 inflammatory factors. The F4/80+ ratio and CD11c+ ratio of primary peritoneal macrophages were determined by flow cytometry. The expressions of p-AMPK and TLR4 were detected by Western blot. The cytoplasmic and nuclear distributions of NFκB p65 were observed by confocal microscopy. The binding of TLR4 to MyD88 was tested by CoIP, and the affinity of BBR for TLR4 was assessed by molecular docking. RESULTS: Upon exposure to LPS, the secretion of TNF-α and transcription of inflammatory factors in macrophages increased, cell morphology changed and protrusions appeared gradually, the proportion of F4/80+CD11c+ M1 macrophages increased, and the nuclear distribution of NFκB p65 increased. BBR pretreatment partially inhibited the changes mentioned above. However, the expression of TLR4 and p-AMPK did not change significantly after LPS intervention for 3 h. Meanwhile, CoIP showed that the interaction between TLR4 and MyD88 increased, and BBR inhibited the binding. Molecular docking suggested that BBR might interact with TLR4. CONCLUSIONS: Inflammatory changes were induced in macrophages after LPS stimulation for 3 h, and BBR pretreatment inhibited inflammatory polarization. BBR might interact with TLR4 and disturb TLR4/MyD88/NFκB signalling pathway, and it might be the mechanism by which BBR attenuated inflammation in the early phase.

Incidental pulmonary embolism in suspected stroke patients undergoing carotid CT angiography.

PURPOSE: The purpose of this study was to investigate the prevalence of incidental pulmonary embolism (IPE) in suspected stroke patients receiving carotid computed tomography angiography (CTA) and its characteristics. MATERIALS AND METHODS: A total of 4873 cases receiving carotid CTA between January 2013 and December 2016 were retrospectively reassessed by one radiologist. Patients with previous or suspected PE were excluded. The remaining prior contrast-enhanced carotid CTA studies were regarded as a "potentially incidental" IPE when a filling defect was found in one or more pulmonary arteries and subjected to the other two thoracic radiologists independently for reviewing and assessing for characteristics of the IPE and the image quality of the PE. The differences were noted between inpatients and outpatients in prevalence of IPE. Characteristics of the patients with IPE were also studied in terms of gender, age, as well as clinical indication. RESULTS: The prevalence of IPE among these suspected stroke patients was 0.8% on carotid CT angiography, and 24 (96%) of all IPEs had not been previously diagnosed by the original reporting radiologists. Most of the IPEs were at the lobar or segmental levels, single and in right upper lobe of pulmonary arteries. In most of the cases, the reviewing radiologists judged the contrast bolus as good. The outpatient group had a lower percentage of patients with IPE when compared with the inpatient counterpart (p = 0.024). The prevalence of IPE in patients with suspected stroke was higher with the increasing of age (p = 0.013). CONCLUSIONS: IPE can occur in suspected stroke patients on carotid CT angiography, and most of them have been previously neglected in clinical practice. Radiologists should check the higher pulmonary arterial vasculature carefully on the contrast-enhanced carotid CTA scans.

The expression profile and promoter analysis of ß-N-acetylglucosaminidases in the silkworm Bombyx mori.

ß-N-acetylglucosaminidase (GlcNAcase) is a key enzyme in the chitin decomposition process. In this study, we investigated the gene expression profile of GlcNAcases and the regulation mechanism for one of these genes, BmGlcNAcase1, in the silkworm. We performed sequence analysis of GlcNAcase. Using dual-spike-in qPCR method, we examined the expression of Bombyx ß-N-acetylglucosaminidases (BmGlcNAcases) in various tissues of silkworm as well as expression changes after stimulation with ecdysone. Using Bac-to-Bac system and luciferase reporter vectors, we further analyzed the promoter sequence of BmGlcNAcase1. The results showed that these proteins have a highly conserved catalytic domain. The expression levels of the BmGlcNAcase genes varied in different tissues, and were increased 48 h after exposure to ecdysone. BmGlcNAcase1 gene promoter with 5'-end serial deletions showed different levels of activity in various tissues, higher in the blood, skin and fat body. Deletion of the region from -347 to -223 upstream of BmGlcNAcase-1 gene abolished its promoter activity. This region contains the binding sites for key transcription factors including Hb, BR-C Z, the HSF and the typical TATA-box element. These results indicate that BmGlcNAcases are expressed at different levels in different tissues of the silkworm, but all are subjected to the regulation by ecdysone. BmGlcNAcase1 promoter analysis has paved a foundation for further study of the gene expression patterns.

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn's disease.

BACKGROUND: Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD. AIM: To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD. METHODS: The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD. RESULTS: A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD (P < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index (ß value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (ß value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression (P < 0.05). CONCLUSION: Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.

[A meta-analysis of preventing bone mineral loss in patients with endometriosis treated by gonadotrophin-releasing hormone analogues with add-back therapy].

OBJECTIVE: To evaluate the role and efficacy of preventing bone mineral loss in patients with endometriosis treated by gonadotrophin-releasing hormone analogues (GnRH-a) combined with add-back therapy. METHODS: Prospective, randomized controlled studies of the use of GnRHa with add-back therapy in treatment of endometriosis were enrolled in this study from Medline, Embase, Cochrane library, China National Knowledge Internet (CNKI), Chinese Biological Medicine Disk (CBM) and Data Base of Wanfang.After quality assessment and data extraction, meta-analysis were conducted in the change of BMD, reproductive hormone (E2) and visual pain score(VAS) by Stata 11.0 software. RESULTS: A total of 785 patients from 13 randomized controlled trail (RCT) studies enrolled in this study after exclude no following up, poor quality and repeat published studies.377 patients were in group of GnRH-a with add-back treatment and 408 patients were in group of GnRna alone.The findinds were showed in meta-analysis: (1) there was a significant difference in percentage change of bone mineral density (BMD) between two groups, the add-back therapy was more effective in prevention of bone loss which was (SMD = 0.223, 95%CI:0.003 to 0.443, P = 0.047). (2) There was no significant difference in the level of reproductive hormone between two groups (SMD = -0.053, 95% CI:-0.479 to 0.373, P = 0.807). (3) There was also no significant difference in the visual pain score between the two groups (SMD = -0.157, 95% CI: -0.474 to 0.160, P = 0.332). CONCLUSIONS: GnRH-a with add-back therapy have been shown to be more effective in preventing loss of BMD than GnRH-a treatment alone.However, the long term effect of preventing BMD should be studied.

[Analysis of Prognosis and Therapeutic Effect of Patients with Thrombotic Thrombocytopenic Purpura].

OBJECTIVE: To summarize the features of clinical and laboratory parameters of thrombotic thrombocytopenic purpura (TTP), and to analyze the factors affecting the prognosis and therapeutic effect during the acute phase of the disease. METHODS: The etiology, clinical features, laboratory parameters, treatment regimens and other data of 59 TTP patients admitted to Hunan Provincial People's Hospital were retrospectively analyzed. And the differences of each variable between the death group and the survival group were compared, the correlations between each variable and prognosis, as well as the therapeutic effect of the acute phase patients were analyzed. RESULTS: Among the 59 cases of TTP, one 4-year-old boy was inherited TTP, the other 58 cases were acquired TTP (39 cases were idiopathic TTP and 19 were secondary TTP), including 27 males and 31 females, with a median age of 54 (11-84) years old. 36 patients were tested for von Willebrand factor cleaving protease (ADAMTS13) activity, and 34 patients (94.44%) had decreased ADAMTS13 activity. There was a statistical difference in the activity of ADAMTS13 between idiopathic and secondary TTP patients (P<0.001). There were statistical differences in factors such as age (64 vs 51 years), ALT/AST ratio (0.61 vs 0.36), therapeutic plasma exchange (TPE) times (3 times vs 8 times), and TPE duration (3 d vs 9 d) between the death and survival groups. Multivariate analysis showed that total times of TPE (OR=5.175,95%CI: 1.169-22.914, P=0.030), ALT/AST ratio (OR=4.387, 95%CI: 1.019-18.891, P=0.047) were associated with mortality. COX regression analysis showed that degree of neuropsychiatric disorder (HR=0.200, 95%CI: 0.084-0.474, P<0.001), days from onset to initiation of TPE (HR=0.288, 95%CI: 0.114-0.726, P=0.008), treatment regimen (HR=0.336, 95%CI: 0.125-0.902, P=0.030) were associated with platelet recovery and therapeutic effect in the acute phase of the patients. CONCLUSION: TTP patients with high ALT/AST ratio have a higher mortality rate. Patients with enough times and full course of TPE have lower mortality rate. Poor therapeutic effect were found in TTP patients with severe neuropsychiatric disorders, delayed diagnosis and treatment, and who added rituximab when TPE was ineffective.

Berberine enhances the function of db/db mice islet ß cell through GLP-1/GLP-1R/PKA signaling pathway in intestinal L cell and islet α cell.

Background: The evidence on berberine stimulating the secretion of GLP-1 in intestinal L cell has been studied. However, few research has explored its role on generating GLP-1 of islet α cell. Our experiment aims to clarify the mechanism of berberine promoting the secretion of GLP-1 in intestinal L cell and islet α cell, activating GLP-1R and its downstream molecules through endocrine and paracrine ways, thus improving the function of islet ß cell and treating T2DM. Methods: After confirming that berberine can lower blood glucose and improve insulin resistance in db/db mice, the identity maintenance, proliferation and apoptosis of islet cells were detected by immunohistochemistry and immunofluorescence. Then, the activation of berberine on GLP-1/GLP-1R/PKA signaling pathway was evaluated by Elisa, Western blot and PCR. Finally, this mechanism was verified by in vitro experiments on Min6 cells, STC-1 cells and aTC1/6 cells. Results: Berberine ameliorates glucose metabolism in db/db mice. Additionally, it also increases the number and enhances the function of islet ß cell. This process is closely related to improve the secretion of intestinal L cell and islet α cell, activate GLP-1R/PKA signaling pathway through autocrine and paracrine, and increase the expression of its related molecule such as GLP-1, GLP-1R, PC1/3, PC2, PKA, Pdx1. In vitro, the phenomenon that berberine enhanced the GLP-1/GLP-1R/PKA signal pathway had also been observed, which confirmed the results of animal experiments. Conclusion: Berberine can maintain the identity and normal function of islet ß cell, and its mechanism is related to the activation of GLP-1/GLP-1R/PKA signal pathway in intestinal L cell and islet α cell.

Efficacy and safety of Huangqi Jianzhong decoction in the treatment of chronic atrophic gastritis: A meta-analysis.

BACKGROUND: Chronic atrophic gastritis is a persistent disorder of the digestive system where the gastric mucosa epithelium and glands undergo atrophy, leading to a decrease in their number and thinning of the gastric mucosa. It is worth noting that the prevalence of chronic atrophic gastritis is higher in China compared to the global average, and it is also considered a precancerous condition for gastric cancer. AIM: To evaluate the efficacy of Huangqi Jianzhong decoction in treating chronic atrophic gastritis. Chronic atrophic gastritis is a persistent illness characterized by the progressive disappearance of healthy gastric glands due to repeated injury. Huangqi Jianzhong decoctions are widely used in China to treat chronic atrophic gastritis. However, there is limited scientific evidence regarding their efficacy in treating this illness. METHODS: The present meta-analysis adhered to the PRISMA guidelines and used the Cochrane Collaboration methodology. We performed a comprehensive search for clinical trials investigating the use of Huangqi Jianzhong decoction in treating chronic atrophic gastritis published until January 2023. The risk of bias and the quality of the included studies were evaluated using the Cochrane Handbook guidelines. Finally, a meta-analysis was conducted using the RevMan 5.4 software. RESULTS: This study included a total of 13 articles, comprising 1269 samples. The meta-analysis was conducted on these 13 articles, yielding the following results: I2 = 0%, P = 0.60, [RR = 1.24, 95%CI: 1.18 to 1.30, P < 0.00001]. The forest plot analysis of the Helicobacter pylori clearance rate revealed I2 = 0%, P = 0.36, [RR = 1.20, 95%CI: 1.05 to 1.38, P = 0.009]. The forest plot of PG-I level showed I2 = 99%, P < 0.00001, [MD = 4.99, 95%CI: -1.59 to 11.58, P = 0.14]. The forest plot of stomach pain demonstrated I2 = 54%, P = 0.04, [MD = -0.63, 95%CI: -0.68 to -0.58, P < 0.00001]. The forest plot of reflux indicated I2 = 82%, P = 0.0009, [MD = -0.48, 95%CI: -0.63 to -0.33, P < 0.00001]. The forest plot of recurrence rate exhibited I2 = 0%, P = 0.92, [RR = 0.15, 95%CI: 0.04 to 0.66, P = 0.01]. The forest plot of adverse reactions showed no heterogeneity in outcome data, [RR = 1.07, 95%CI: 0.53 to 2.17, P = 0.86]. CONCLUSION: This study demonstrated that Huangqi Jianzhong decoction improved various factors in adults with chronic atrophic gastritis. These factors included the total effective rate, Helicobacter pylori clearance rate, symptoms such as stomachache and acid reflux alleviation, and recurrence rates.

Alleviating effect of lycorine on CFA­induced arthritic pain via inhibition of spinal inflammation and oxidative stress.

Chronic pain is the primary symptom of osteoarthritis affecting a patient's quality of life. Neuroinflammation and oxidative stress in the spinal cord contribute to arthritic pain and represent ideal targets for pain management. In the present study, a model of arthritis was established by intra-articular injection of complete Freund's adjuvant (CFA) into the left knee joint in mice. After CFA inducement, knee width and pain hypersensitivity in the mice were increased, motor disability was impaired, spinal inflammatory reaction was induced, spinal astrocytes were activated, antioxidant responses were decreased, and glycogen synthase kinase 3ß (GSK-3ß) activity was inhibited. To explore the potential therapeutic options for arthritic pain, lycorine was intraperitoneally injected for 3 days in the CFA mice. Lycorine treatment significantly reduced mechanical pain sensitivity, suppressed spontaneous pain, and recovered motor coordination in the CFA-induced mice. Additionally, in the spinal cord, lycorine treatment decreased the inflammatory score, reduced NOD-like receptor protein 3 inflammasome (NLRP3) activity and IL-1ß expression, suppressed astrocytic activation, downregulated NF-κB levels, increased nuclear factor erythroid 2-related factor 2 expression and superoxide dismutase activity. Furthermore, lycorine was shown to bind to GSK-3ß through three electrovalent bonds, to inhibit GSK-3ß activity. In summary, lycorine treatment inhibited GSK-3ß activity, suppressed NLRP3 inflammasome activation, increased the antioxidant response, reduced spinal inflammation, and relieved arthritic pain.

[Study on the release and mechanism of carbon nanotubes loaded with verapamil hydrochloride in vitro].

OBJECTIVE: The aim of this study was to load Verapamil Hydrochloride to carboxylated multi-walled carbon nanotubes( c-CNTs) and discuss the mechanism of drug release which could act as an effective basis for c-MWNTs used as drug carriers of controlled and sustained release delivery system. METHODS: Raw CNTs were treated with mixed strong acid to obtain c-CNTs. Raman, IR, SEM and HR-TEM were used to characterize the CNTs and investigate the loading sites for drugs. The release behavior of the drug delivery system in vitro and the release model were studied. RESULTS: The raw CNTs were successfully grafted with carboxyl group by acid treatment. The water-soluble ability of c-CNTs was greatly improved. The length of c-CNTs was 200-300nm. Meanwhile, the ends of c-CNTs were opened. The results of the drug loading experiment showed that the more adding drugs, the larger loading content of drugs. Most of the drugs were loaded into the inner pores of c-CNTs when adding drugs was no more than 0.1 as quantity as c-CNTs. As the quantity of adding drugs increased, the drugs were loaded both in the inner pores and on the out-wall of c-CNTs. The release results in vitro showed release mechanism had something with the quantity of adding drugs. CONCLUSION: C-CNTs can be used as carriers of sustained and controlled release delivery system. Ideal release behavior of drugs can be achieved by choosing appropriate formula.

Ban-xia-xie-xin-tang ameliorates hepatic steatosis by regulating Cidea and Cidec expression in HFD-fed mice.

BACKGROUND: Ban-xia-xie-xin-tang (BXXXT) has been applied in treating metabolic diseases, such as nonalcohol fatty liver disease, diabetes mellitus, and obesity. However, the underlying molecular mechanism of BXXXT in treating diabetes mellitus is unknown. PURPOSE: To clarify the underlying molecular mechanism of BXXXT in alleviating hepatic steatosis in high-fat diet (HFD)-fed mice. METHODS: After 12 weeks of HFD treatment, mice were administered BXXXT for 4 weeks. The main chemical components of BXXXT were identified by UPLC-TQ-MS/MS. Indicators associated with insulin resistance and lipid metabolism were detected. The effect of improving glucose and lipid metabolism between BXXXT and the different components was compared. Differentially expressed genes (DEGs) were identified by hepatic transcriptomics. Key DEGs and proteins were further detected by real-time quantitative polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence staining. LDs and mitochondria were detected by transmission electron microscopy. RESULTS: First of all, our data demonstrated that the capacity to improve glucose and lipid metabolism for BXXXT was significantly superior to different components of BXXXT. BXXXT was found to improve HFD-induced insulin resistance. Moreover, BXXXT decreased weight, serum/hepatic triglycerides, total cholesterol, and FFAs to alleviate HFD-induced hepatic steatosis. According to the results of the hepatic transcription, Cidea and Cidec were identified as critical DEGs for promoting LD fusion and reducing FFAs ß-oxidation in mitochondria and peroxisome resulting in hepatic steatosis, which was reversed by BXXXT. CONCLUSION: BXXXT ameliorates HFD-induced hepatic steatosis and insulin resistance by increasing Cidea and Cidec-mediated mitochondrial and peroxisomal fatty acid oxidation, which may provide a potential strategy for therapy of NAFLD and T2DM.

The rapid appearance of homostyly in a cultivated distylous population of Primula forbesii.

Evolutionary breakdown from rigorous outbreeding to self-fertilization frequently occurs in angiosperms. Since the pollinators are not necessary, self-compatible populations often reduce investment in floral display characteristics and pollination reward. Primula forbesii is a biennial herb with distribution restricted to southwest China; it was initially a self-incompatible distylous species, but after 20 years of artificial domestication, homostyly appeared. This change in style provides an ideal material to explore the time required for plant mating systems to adapt to new environmental changes and test whether flower attraction has reduced following transitions to selfing. We did a survey in wild populations of P. forbesii where its seeds were originally collected 20 years ago and recorded the floral morph frequencies and morphologies. The floral morphologies, self-incompatibility, floral scent, and pollinator visitation between distyly and homostyly were compared in greenhouse. Floral morph frequencies of wild populations did not change, while the cultivated population was inclined to L-morph and produced homostyly. Evidence from stigma papillae and pollen size supports the hypothesis that the homostyly possibly originated from mutations of large effect genes in distylous linkage region. Transitions to self-compatible homostyly are accompanied by smaller corolla size, lower amounts of terpenoids, especially linalool and higher amounts of fatty acid derivatives. The main pollinators in the greenhouse were short-tongued Apis cerana. However, homostyly had reduced visiting frequency. The mating system of P. forbesii changed rapidly in just about 20 years of domestication, and our findings confirm the hypothesis that the transition to selfing is accompanied by decreased flower attraction.

Characterizing Sensorimotor-Related Area Abnormalities in Amyotrophic Lateral Sclerosis: An Intravoxel Incoherent Motion Magnetic Resonance Imaging Study.

RATIONALE AND OBJECTIVES: To investigate the microperfusion and water molecule diffusion alterations in sensorimotor-related areas in amyotrophic lateral sclerosis (ALS) using intravoxel incoherent motion (IVIM) magnetic resonance imaging. MATERIALS AND METHODS: IVIM data were obtained from 43 ALS patients and 31 controls. This study employed the revised ALS Functional Rating Scale (ALSFRS-R) in evaluating disease severity. IVIM-derived metrics were calculated, including diffusion coefficient (D), pseudo-diffusion coefficient, and perfusion fraction. Conventional apparent diffusion coefficient was also computed. Atlas-based analysis was conducted to detect between-group difference in these metrics in sensorimotor-related gray/white matter areas. Spearman correlation analysis was employed to establish correlation between various metrics and ALSFRS-R. RESULTS: ALS patients had perfusion fraction (× 10-3) reduction in the left presupplementary motor area (60.72 ± 16.15 vs. 71.15 ± 12.98, p = 0.016), right presupplementary motor area (61.35 ± 17.02 vs. 72.18 ± 14.22, p = 0.016), left supplementary motor area (55.73 ± 12.29 vs. 64.12 ± 9.17, p = 0.015), and right supplementary motor area (56.53 ± 11.93 vs. 63.67 ± 10.03, p = 0.020). Patients showed D (× 10-6 mm2/s) increase in a white matter tract projecting to the right ventral premotor cortex (714.20 ± 39.75 vs. 691.01 ± 24.53, p = 0.034). A negative correlation between D of right ventral premotor cortex tract and ALSFRS-R score was observed (r = -0.316, p = 0.039). CONCLUSION: These findings suggest aberrant microperfusion and water molecule diffusion in the sensorimotor-related areas in ALS patients, which are associated with motor impairment in ALS.

Quality of reporting of randomized clinical trials in tai chi interventions-a systematic review.

Objectives. To evaluate the reporting quality of published randomized clinical trials (RCTs) in the Tai Chi literature following the publication of the CONSORT guidelines in 2001. Data Sources. The OVID MEDLINE and PUBMED databases. Review Methods. To survey the general characteristics of Tai Chi RCTs in the literature, we included any report if (i) it was an original report of the trial; (ii) its design was RCT; (iii) one of the treatments being tested was Tai Chi; and (iv) it was in English. In addition, we assessed the reporting quality of RCTs that were published between 2002 and 2007, using a modified CONSORT checklist of 40 items. The adequate description of Tai Chi interventions in these trials was examined against a 10-item checklist adapted from previous reviews. Results. The search yielded 31 Tai Chi RCTs published from 2002 to 2007 and only 11 for 1992-2001. Among trials published during 2002-2007, the most adequately reported criteria were related to background, participant eligibility and interpretation of the study results. Nonetheless, the most poorly reported items were associated with randomization allocation concealment, implementation of randomization and the definitions of period of recruitment and follow-up. In addition, only 23% of RCTs provided adequate details of Tai Chi intervention used in the trials. Conclusion. The findings in this review indicated that the reporting quality of Tai Chi intervention trials is sub-optimal. Substantial improvement is required to meet the CONSORT guidelines and allow assessment of the quality of evidence. We believe that not only investigators, but also journal editors, reviewers and funding agencies need to follow the CONSORT guidelines to improve the standards of research and strengthen the evidence base for Tai Chi and for complementary and alternative medicine.

Targeted Methylation of the LncRNA NEAT1 Suppresses Malignancy of Renal Cell Carcinoma.

Long-chain non-coding RNA (LncRNA) has been found to play an important role in the regulation of the occurrence and progression of renal cell carcinoma (RCC). In this study, we demonstrated that LncRNA NEAT1 expression and m6A methylation level was decreased in RCC tissues. Further, the downregulated expression level of LncRNA NEAT1 was associated with poor prognosis for RCC patients. Then we used CRIPSR/dCas13b-METTL3 to methylate LncRNA NEAT1 in RCC cells. The results showed that the expression level of LncRNA NEAT1 was upregulated after methylated by dCas13b-METTL3 in RCC cells. And the proliferation and migration ability of RCC cells was decreased after methylated LncRNA NEAT1. Finally, we examined the effect of LncRNA NEAT1 hypermethylation on the transcriptome. We found differentially expressed genes in RCC cells were associated with "cGMP-PKG signaling pathway", "Cell adhesion molecules" and "Pathways in cancer". In conclusion, CRISPR/Cas13b-METTL3 targeting LncRNA NEAT1 m6A methylation activates LncRNA NEAT1 expression and provides a new target for treatment of RCC.