Catalytic Asymmetric Desymmetrization of Cyclic 1,3-Diketones Using Chiral Boro-phosphates.

Herein, we report a chiral boro-phosphate-catalyzed reductive amination for the desymmetrization of 2,2-disubstituted 1,3-cyclopentadiones with pinacolborane as the reducing agent, delivering chiral ß-amino ketones with an all-carbon quaternary stereocenter in good yields (≤94%), high enantioselectivities (≤97% ee), and excellent diastereoselectivities (>20:1 dr). This reaction has a broad substrate scope and high functional group tolerance. The importance of the chiral products was also demonstrated through the preparation of multifunctional building blocks and heterocycles.

The value of ultrasound measurement of muscle thickness at different sites and shear wave elastography in Parkinson's disease with sarcopenia: a pilot study.

Background: Patients with Parkinson's disease (PD) and sarcopenia often exhibit resilience, frailty, disability, and depression, highlighting the complex and interrelated nature of these conditions. Objective: Despite the presence of clinical manifestations of muscle atrophy in both PD and sarcopenia, accurately discerning the coexistence of sarcopenia in PD patients remains a challenging task with significant implications for treatment strategies and prognostic assessments. This study aims to elucidate the specific ultrasonic diagnostic parameters associated with PD accompanied by sarcopenia through a comparative analysis of muscle ultrasound parameters in patients with PD, thereby presenting a novel approach for rapid identification of this condition. Methods: A total of 110 participants were enrolled in this study, including patients with PD and control subjects. Demographic data, clinical characteristics, physical performance tests, appendicular skeletal muscle mass index (ASMI), bioelectrical impedance analysis and muscle ultrasound measurements were collected from all participants. The muscle ultrasound measurements encompassed assessments of muscle thickness, pennation angle and shear wave elastography at various anatomical sites. Results: Parkinson's disease patients exhibited decreased muscle strength and physical performance, and increased shear wave elastography value. In PD patients with sarcopenia, body circumference, including calf circumference, mid-arm circumference, Waist-to-Hip Ratio and body mass index (BMI) were all significantly decreased. Biceps brachii muscle thickness (MT) and gastrocnemius MT decreased in PD patients with sarcopenia and low ASMI. Binary logistic regression analysis revealed that male PD patients, BMI and gastrocnemius MT were predictive factors for ASMI in PD patients. Conclusion: Biceps brachii MT and gastrocnemius MT are important indicators for distinguishing whether PD patients have sarcopenia. Male patients, low BMI and gastrocnemius MT were identified as valid predictors of low ASMI in PD patients. The findings of this study provide important insights into the use of muscle ultrasound in the diagnosis of PD with sarcopenia.

Value of mammographic microcalcifications and MRI-enhanced lesions in the evaluation of residual disease after neoadjuvant therapy for breast cancer.

Background: Microcalcifications persist even if a patient with breast cancer achieves pathologic complete response (pCR) as confirmed by surgery after neoadjuvant treatment (NAT). In practice, surgeons tend to remove all the microcalcifications. This study aimed to explore the correlation between changes in the extent of microcalcification after NAT and pathological tumor response and compare the accuracy of mammography (MG) and magnetic resonance imaging (MRI) in predicting the size of residual tumors. Methods: This was a retrospective study which included a consecutive series of patients in Guangdong Provincial People's Hospital. Between January 2010 and January 2020, 127 patients with breast cancer and Breast Imaging Reporting and Data System (BI-RADS) 4-5 microcalcifications were included in this study. The maximum diameter of the microcalcifications on MG and lesion enhancement on MRI pre- and post-NAT were measured. The correlations between the changes in residual microcalcifications on MG and pCR were analyzed. Intraclass correlation coefficients (ICCs) were computed between the extent of the residual microcalcifications, residual enhancement, and residual tumor size. Results: There were no statistically significant differences in the changes in microcalcifications after NAT according to the RECIST criteria on MRI (P=0.09) and Miller-Payne grade (P=0.14). MRI showed a higher agreement than did residual microcalcifications on MG in predicting residual tumor size (ICC: 0.771 vs. 0.097). Conclusions: MRI is more accurate for evaluating residual tumor size in breast cancer. In our study, the extent of microcalcifications on MG after NAT had nearly no correlation with the pathological size of the residual tumor. Therefore, residual tumors with microcalcifications may not necessarily be a contraindication to breast-conserving surgery.

Use of Pretreatment Multiparametric MRI to Predict Tumor Regression Pattern to Neoadjuvant Chemotherapy in Breast Cancer.

RATIONALE AND OBJECTIVES: To develop an easy-to-use model by combining pretreatment MRI and clinicopathologic features for early prediction of tumor regression pattern to neoadjuvant chemotherapy (NAC) in breast cancer. MATERIALS AND METHODS: We retrospectively analyzed 420 patients who received NAC and underwent definitive surgery in our hospital from February 2012 to August 2020. Pathologic findings of surgical specimens were used as the gold standard to classify tumor regression patterns into concentric and non-concentric shrinkage. Morphologic and kinetic MRI features were both analyzed. Univariable and multivariable analyses were performed to select the key clinicopathologic and MRI features for pretreatment prediction of regression pattern. Logistic regression and six machine learning methods were used to construct prediction models, and their performance were evaluated with receiver operating characteristic curve. RESULTS: Two clinicopathologic variables and three MRI features were selected as independent predictors to construct prediction models. The apparent area under the curve (AUC) of seven prediction models were in the range of 0.669-0.740. The logistic regression model yielded an AUC of 0.708 (95% confidence interval [CI]: 0.658-0.759), and the decision tree model achieved the highest AUC of 0.740 (95% CI: 0.691-0.787). For internal validation, the optimism-corrected AUCs of seven models were in the range of 0.592-0.684. There was no significant difference between the AUCs of the logistic regression model and that of each machine learning model. CONCLUSION: Prediction models combining pretreatment MRI and clinicopathologic features are useful for predicting tumor regression pattern in breast cancer, which can assist to select patients who can benefit from NAC for de-escalation of breast surgery and modify treatment strategy.

Using Machine Learning Methods to Assess Lymphovascular Invasion and Survival in Breast Cancer: Performance of Combining Preoperative Clinical and MRI Characteristics.

BACKGROUND: Preoperative assessment of lymphovascular invasion (LVI) in invasive breast cancer (IBC) is of high clinical relevance for treatment decision-making and prognosis. PURPOSE: To investigate the associations of preoperative clinical and magnetic resonance imaging (MRI) characteristics with LVI and disease-free survival (DFS) by using machine learning methods in patients with IBC. STUDY TYPE: Retrospective. POPULATION: Five hundred and seventy-five women (range: 24-79 years) with IBC who underwent preoperative MRI examinations at two hospitals, divided into the training (N = 386) and validation datasets (N = 189). FIELD STRENGTH/SEQUENCE: Axial fat-suppressed T2-weighted turbo spin-echo sequence and dynamic contrast-enhanced with fat-suppressed T1-weighted three-dimensional gradient echo imaging. ASSESSMENT: MRI characteristics (clinical T stage, breast edema score, MRI axillary lymph node status, multicentricity or multifocality, enhancement pattern, adjacent vessel sign, and increased ipsilateral vascularity) were reviewed independently by three radiologists. Logistic regression (LR), eXtreme Gradient Boosting (XGBoost), k-Nearest Neighbor (KNN), and Support Vector Machine (SVM) algorithms were used to establish the models by combing preoperative clinical and MRI characteristics for assessing LVI status in the training dataset, and the methods were further applied in the validation dataset. The LVI score was calculated using the best-performing of the four models to analyze the association with DFS. STATISTICAL TESTS: Chi-squared tests, variance inflation factors, receiver operating characteristics (ROC), Kaplan-Meier curve, log-rank, Cox regression, and intraclass correlation coefficient were performed. The area under the ROC curve (AUC) and hazard ratios (HR) were calculated. A P-value <0.05 was considered statistically significant. RESULTS: The model established by the XGBoost algorithm had better performance than LR, SVM, and KNN models, achieving an AUC of 0.832 (95% confidence interval [CI]: 0.789, 0.876) in the training dataset and 0.838 (95% CI: 0.775, 0.901) in the validation dataset. The LVI score established by the XGBoost model was an independent indicator of DFS (adjusted HR: 2.66, 95% CI: 1.22-5.80). DATA CONCLUSION: The XGBoost model based on preoperative clinical and MRI characteristics may help to investigate the LVI status and survival in patients with IBC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Asymmetric Rubottom-Type Oxidation Catalyzed by Chiral Calcium Phosphates.

Invited for the cover of this issue is the group of Jon C. Antilla at Zhejiang Sci-Tech University. The image depicts asymmetric Rubottom-type oxidation catalyzed by chiral calcium phosphates. Read the full text of the article at 10.1002/chem.202203720.

Asymmetric Rubottom-Type Oxidation Catalyzed by Chiral Calcium Phosphates.

A highly efficient catalytic asymmetric Rubottom-type oxidation is described. Using meta-chloroperbenzoic acid (m-CPBA) as the oxidant and chiral calcium phosphate as the catalyst, the facile transformation enables direct hydroxylation of N-Boc oxindoles and ß-ketoesters in high yields (up to 99 %) and in a highly enantioenriched fashion (up to >99 % ee). The application of the established method was demonstrated by the synthesis of a pharmaceutically important 3-hydroxyoxindole with excellent enantiocontrol.

Asymmetric Reductive Amination with Pinacolborane Catalyzed by Chiral SPINOL Borophosphates.

The catalytic asymmetric reductive amination of ketones with pinacolborane employing chiral SPINOL-derived borophosphates as catalysts has been realized. A series of chiral amine derivatives bearing multiple functional groups were obtained in good to excellent yields and enantioselectivities (up to 97% yield, 98% ee) under mild reaction conditions. Moreover, the synthetic applicability of the established method has been demonstrated by the asymmetric synthesis of (R)-Fendiline.

Coupling Effect of Non-Ignition Impact and Heat on the Decay of FOX-7.

Non-ignition impact and heat stimuli are the most common external stimuli loaded on energetic materials. Nevertheless, there is thereby an urgent need, but it is still a significant challenge to comprehend their coupling effects on the decay and safety mechanisms of energetic materials. Then, reactive molecular dynamics simulation was employed to mimic practical situations and reveal the impact heat coupling effect on the decay mechanism of FOX-7. The temperature and the degree of compression of the crystal caused by the impact are considered variables in the simulation. Both increasing the degree of compression and elevating the temperature promotes the decay of FOX-7. However, their underlying response mechanism is not the same. The acceleration of decomposition is due to the elevated potential energy of the FOX-7 molecules because of elevating the temperature. In addition to the elevated potential energy of the molecule, the main contribution to the decomposition from the compression is to change the decomposition path. The results of the analysis show that compression reduces the stability of the C=C bond, so that chemical reactions related to the double bond occur. In addition, interestingly, the compression along the c direction has an almost equal effect on the final product as the compression along the b direction. Finally, the decay reaction networks are proposed to provide insights into the decomposition mechanism on atomic level. All these findings are expected to pave a way to understand the underlying response mechanism for the FOX-7 against external stimuli.

Multiple-parameter MRI after neoadjuvant systemic therapy combining clinicopathologic features in evaluating axillary pathologic complete response in patients with clinically node-positive breast cancer.

OBJECTIVE: This study aimed to evaluate axillary pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) in clinically node-positive breast cancer (BC) patients based on post-NST multiple-parameter MRI and clinicopathological characteristics. METHODS: In this retrospective study, females with clinically node-positive BC who received NST and followed by surgery between January 2017 and September 2021 were included. All axillary lymph nodes (ALNs) on MRI were matched with pathology by ALN markers or sizes. MRI morphological parameters, signal intensity curve (TIC) patterns and apparent diffusion coefficient (ADC) values of post-NST ALNs were measured. The clinicopathological characteristics was also collected and analyzed. Univariable and multivariable logistic regression analyses were performed to evaluate the independent predictors of axillary pCR. RESULTS: Pathologically confirmed 137 non-pCR ALNs in 71 patients and 87 pCR ALNs in 87 patients were included in this study. Cortical thickness, fatty hilum, and TIC patterns of ALNs, hormone receptor, and human epidermal growth factor receptor 2 (HER2) status were significantly different between the two groups (all, p < 0.05). There was no significant difference for ADC values (p = 0.875). On multivariable analysis, TIC patterns (odds ratio [OR], 2.67, 95% confidence interval [CI]: 1.33, 5.34, p = 0.006), fatty hilum (OR, 2.88, 95% CI:1.39, 5.98, p = 0.004), hormone receptor (OR, 8.40, 95% CI: 2.48, 28.38, p = 0.001) and HER2 status (OR, 8.57, 95% CI: 3.85, 19.08, p < 0.001) were identified as independent predictors associated with axillary pCR. The area under the curve of the multivariate analysis using these predictors was 0.85 (95% CI: 0.79, 0.91). CONCLUSION: Combining post-NST multiple-parameter MRI and clinicopathological characteristics allowed more accurate identification of BC patients who had received axillary pCR after NST. ADVANCES IN KNOWLEDGE: A combined model incorporated multiple-parameter MRI and clinicopathologic features demonstrated good performance in evaluating axillary pCR preoperatively and non-invasively.

MRI characteristics of breast edema for assessing axillary lymph node burden in early-stage breast cancer: a retrospective bicentric study.

OBJECTIVES: To investigate whether breast edema characteristics at preoperative T2-weighted imaging (T2WI) could help evaluate axillary lymph node (ALN) burden in patients with early-stage breast cancer. METHODS: This retrospective study included women with clinical T1 and T2 stage breast cancer and preoperative MRI examination in two independent cohorts from May 2014 to December 2020. Low (< 3 LNs+) and high (≥ 3 LNs+) pathological ALN (pALN) burden were recorded as endpoint. Breast edema score (BES) was evaluated at T2WI. Univariable and multivariable analyses were performed by the logistic regression model. The added predictive value of BES was examined utilizing the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 1092 patients were included in this study. BES was identified as the independent predictor of pALN burden in primary (n = 677) and validation (n = 415) cohorts. The analysis using MRI-ALN status showed that BES significantly improved the predictive performance of pALN burden (AUC: 0.65 vs 0.71, p < 0.001; IDI = 0.045, p < 0.001; continuous NRI = 0.159, p = 0.050). These results were confirmed in the validation cohort (AUC: 0.64 vs 0.69, p = 0.009; IDI = 0.050, p < 0.001; continuous NRI = 0.213, p = 0.047). Furthermore, BES was positively correlated with biologically invasive clinicopathological factors (p < 0.05). CONCLUSIONS: In individuals with early-stage breast cancer, preoperative MRI characteristics of breast edema could be a promising predictor for pALN burden, which may aid in treatment planning. KEY POINTS: • In this retrospective study of 1092 patients with early-stage breast cancer from two cohorts, the MRI characteristic of breast edema has independent and additive predictive value for assessing axillary lymph node burden. • Breast edema characteristics at T2WI positively correlated with biologically invasive clinicopathological factors, which may be useful for preoperative diagnosis and treatment planning for individual patients with breast cancer.

Gender-specific impact of cognitive impairment on all-cause mortality in older persons: A meta-analysis.

BACKGROUND: Gender-specific impact of cognitive impairment on survival in the general population remains controversial. The objective of this meta-analysis was to assess the gender difference in the impact of cognitive impairment on all-cause mortality in the general population. METHODS: Two reviewers independently searched PubMed and Embase databases up to September 30, 2021 for cohort studies that reported gender-specific impact of cognitive impairment detected by the mini-mental state examination (MMSE) on all-cause mortality in elderly general population (aged ≥60 years) in the same study. RESULTS: Nine articles reporting on 10 studies with a total of 52,134 individuals were included. The pooled multivariate-adjusted risk ratio (RR) of all-cause mortality associated with cognitive impairment compared with those without was 1.48 (95% confidence interval [CI] 1.36-1.61) in women and 1.34 (95% CI 1.24-1.44) in men, after adjusting for potential confounding. The pooled multivariate-adjusted female-to-male ratio of relative risk of all-cause mortality was 1.08 (95% CI 1.02-1.14) for individuals with cognitive impairment versus those without. CONCLUSIONS: Cognitive impairment detected by the MMSE is associated with an increased risk of all-cause mortality in older aged women than in men from the general population, even after adjusting sociodemographic factors. Compared with men with cognitive impairment, women with cognitive impairment had an 8% higher risk of all-cause mortality. These findings highlight the importance of early detection and management of cognitive impairment in older adults, particularly in women.

Machine Learning to Predict Long-Term Cardiac-Relative Prognosis in Patients With Extra-Cardiac Vascular Disease.

Aim: Patients with ischemic stroke (IS), transient ischemic attack (TIA), and/or peripheral artery disease (PAD) represent a population with an increased risk of coronary artery disease. Prognostic risk assessment to identify those with the highest risk that may benefit from more intensified treatment remains challenging. To explore the feasibility and capability of machine learning (ML) to predict long-term adverse cardiac-related prognosis in patients with IS, TIA, and/or PAD. Methods: We analyzed 636 consecutive patients with a history of IS, TIA, and/or PAD. All patients underwent a coronary CT angiography (CCTA) scan. Thirty-five clinical data and 34 CCTA metrics underwent automated feature selection for ML model boosting. The clinical outcome included all-cause mortality (ACM) and major adverse cardiac events (MACE) (ACM, unstable angina requiring hospitalization, non-fatal myocardial infarction (MI), and revascularization 90 days after the index CCTA). Results: During the follow-up of 3.9 ± 1.6 years, 21 patients had unstable angina requiring hospitalization, eight had a MI, 23 had revascularization and 13 deaths. ML demonstrated a significant higher area-under-curve compared with the modified Duke index (MDI), segment stenosis score (SSS), segment involvement score (SIS), and Framingham risk score (FRS) for the prediction of ACM (ML:0.92 vs. MDI:0.66, SSS:0.68, SIS:0.67, FRS:0.51, all P < 0.001) and MACE (ML:0.84 vs. MDI:0.82, SSS:0.76, SIS:0.73, FRS:0.53, all P < 0.05). Conclusion: Among the patients with IS, TIA, and/or PAD, ML demonstrated a better capability of predicting ACM and MCAE than clinical scores and CCTA metrics.

Combining quantitative and qualitative magnetic resonance imaging features to differentiate anorectal malignant melanoma from low rectal cancer.

Background: Distinguishing anorectal malignant melanoma from low rectal cancer remains challenging because of the overlap of clinical symptoms and imaging findings. We aim to investigate whether combining quantitative and qualitative magnetic resonance imaging (MRI) features could differentiate anorectal malignant melanoma from low rectal cancer. Methods: Thirty-seven anorectal malignant melanoma and 98 low rectal cancer patients who underwent pre-operative rectal MRI from three hospitals were retrospectively enrolled. All patients were divided into the primary cohort (N = 84) and validation cohort (N = 51). Quantitative image analysis was performed on T1-weighted (T1WI), T2-weighted (T2WI), and contrast-enhanced T1-weighted imaging (CE-T1WI). The subjective qualitative MRI findings were evaluated by two radiologists in consensus. Multivariable analysis was performed using stepwise logistic regression. The discrimination performance was assessed by the area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI). Results: The skewness derived from T2WI (T2WI-skewness) showed the best discrimination performance among the entire quantitative image features for differentiating anorectal malignant melanoma from low rectal cancer (primary cohort: AUC = 0.852, 95% CI 0.788-0.916; validation cohort: 0.730, 0.645-0.815). Multivariable analysis indicated that T2WI-skewness and the signal intensity of T1WI were independent factors, and incorporating both factors achieved good discrimination performance in two cohorts (primary cohort: AUC = 0.913, 95% CI 0.868-0.958; validation cohort: 0.902, 0.844-0.960). Conclusions: Incorporating T2WI-skewness and the signal intensity of T1WI achieved good performance for differentiating anorectal malignant melanoma from low rectal cancer. The quantitative image analysis helps improve diagnostic accuracy.

Co-Encapsulation of Mitoxantrone and ß-Elemene in Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Leukemia.

Multidrug resistance (MDR) due to P-glycoprotein (P-gp) overexpression is a major obstacle to successful leukemia chemotherapy. The combination of anticancer chemotherapy with a chemosensitizer of P-gp inhibitor is promising to overcome MDR, generate synergistic effects, and maximize the treatment effect. Herein, we co-encapsulated a chemotherapeutic drug of mitoxantrone (MTO) and a P-gp inhibitor of ß-elemene (ßE) in solid lipid nanoparticles (MTO/ßE-SLNs) for reversing MDR in leukemia. The MTO/ßE-SLNs with about 120 nm particle size possessed good colloidal stability and sustained release behavior. For the cellular uptake study, doxorubicin (DOX) was used as a fluorescence probe to construct SLNs. The results revealed that MTO/ßE-SLNs could be effectively internalized by both K562/DOX and K562 cells through the pathway of caveolate-mediated endocytosis. Under the optimized combination ratio of MTO and ßE, the in vitro cytotoxicity study indicated that MTO/ßE-SLNs showed a better antitumor efficacy in both K562/DOX and K562 cells than other MTO formulations. The enhanced cytotoxicity of MTO/ßE-SLNs was due to the increased cellular uptake and blockage of intracellular ATP production and P-gp efflux by ßE. More importantly, the in vivo studies revealed that MTO/ßE-SLNs could significantly prolong the circulation time and increase plasma half-life of both MTO and ßE, accumulate into tumor and exhibit a much higher anti-leukemia effect with MDR than other MTO formulations. These findings suggest MTO/ßE-SLNs as a potential combined therapeutic strategy for overcoming MDR in leukemia.

Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis.

Multifunctional nanomedicines with active targeting and stimuli-responsive drug release function utilizing pathophysiological features of the disease are regarded as an effective strategy for treatment of rheumatoid arthritis (RA). Under the inflammatory environment of RA, activated macrophages revealed increased expression of folate receptor and elevated intracellular reactive oxygen species (ROS) level. In this study, we successfully conjugated folate to polyethylene glycol 100 monostearate as film-forming material and further prepared methotrexate (MTX) and catalase (CAT) co-encapsulated liposomes, herein, shortened to FOL-MTX&CAT-L, that could actively target to activated macrophages. Thereafter, elevated intracellular hydrogen peroxide, the main source of ROS, diffused into liposomes and encapsulated CAT catalyzed the decomposition of hydrogen peroxide into oxygen and water. Continuous oxygen-generation inside liposomes would eventually disorganize its structure and release the encapsulated MTX. We characterized the in vitro drug release, cellular uptake and cytotoxicity studies as well as in vivo pharmacokinetics, biodistribution, therapeutic efficacy and safety studies of FOL-MTX&CAT-L. In vitro results revealed that FOL-MTX&CAT-L possessed sufficient ROS-sensitive drug release, displayed an improved cellular uptake through folate-mediated endocytosis and exhibited a higher cytotoxic effect on activated RAW264.7 cells. Moreover, in vivo results showed prolonged blood circulation time of PEGylated liposomes, enhanced accumulation of MTX in inflamed joints of collagen-induced arthritis (CIA) mice, reinforced therapeutic efficacy and minimal toxicity toward major organs. These results imply that FOL-MTX&CAT-L may be used as an effective nanomedicine system for RA treatment.

NLRP3 inflammasome signaling as an early molecular response is negatively controlled by miR-186 in CFA-induced prosopalgia mice.

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most frequently studied in the central nervous system and has been linked to neuropathic pain. In this study, a post-translational mechanism of microRNA (miR)-186 via regulating the expression of NLRP3 in the complete Freund's adjuvant (CFA)-treated mice was investigated. The injection of CFA was used to induce trigeminal neuropathic pain in mice. miRs microarray chip assay was performed in trigeminal ganglions (TGs). CFA treatment significantly increased the mRNA expression of NLRP3, interleukin (IL)-1ß, and IL-18 in TGs compared to the control group. Moreover, 26 miRs were differentially expressed in TGs from trigeminal neuropathic pain mice, and the expression of miR-186 showed the lowest level of all the miRs. Further examination revealed that NLRP3 was a candidate target gene of miR-186. We delivered miR-186 mimics to CFA-treated mice. The head withdrawal thresholds of the CFA-treated mice were significantly increased by miR-186 mimics injection compared with CFA single treatment. The mRNA and protein expression of NLRP3, IL-1ß, and IL-18 in TGs from trigeminal neuropathic pain mice were significantly inhibited by miR-186 mimics treatment compared to the CFA group. miR-186 was able to suppress the neuropathic pain via regulating the NLRP3 inflammasome signaling.

NLRP3 inflammasome signaling as an early molecular response is negatively controlled by miR-186 in CFA-induced prosopalgia mice

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most frequently studied in the central nervous system and has been linked to neuropathic pain. In this study, a post-translational mechanism of microRNA (miR)-186 via regulating the expression of NLRP3 in the complete Freund's adjuvant (CFA)-treated mice was investigated. The injection of CFA was used to induce trigeminal neuropathic pain in mice. miRs microarray chip assay was performed in trigeminal ganglions (TGs). CFA treatment significantly increased the mRNA expression of NLRP3, interleukin (IL)-1β, and IL-18 in TGs compared to the control group. Moreover, 26 miRs were differentially expressed in TGs from trigeminal neuropathic pain mice, and the expression of miR-186 showed the lowest level of all the miRs. Further examination revealed that NLRP3 was a candidate target gene of miR-186. We delivered miR-186 mimics to CFA-treated mice. The head withdrawal thresholds of the CFA-treated mice were significantly increased by miR-186 mimics injection compared with CFA single treatment. The mRNA and protein expression of NLRP3, IL-1β, and IL-18 in TGs from trigeminal neuropathic pain mice were significantly inhibited by miR-186 mimics treatment compared to the CFA group. miR-186 was able to suppress the neuropathic pain via regulating the NLRP3 inflammasome signaling.