Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis.

Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with giant or multiple nuclei and high DNA content have the properties of cancer stem cell and single PGCCs can individually generate tumours in immunodeficient mice. PGCCs represent a dormant form of cancer cells that survive harsh tumour conditions and contribute to tumour recurrence. Hypoxic mimics, chemotherapeutics, radiation and cytotoxic traditional Chinese medicines can induce PGCCs formation through endoreduplication and/or cell fusion. After incubation, dormant PGCCs can recover from the treatment and produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric cell division. Additionally, PGCCs can resist hypoxia or chemical stress and have a distinct protein signature that involves chromatin remodelling and cell cycle regulation. Dormant PGCCs form the cellular basis for therapeutic resistance, metastatic cascade and disease recurrence. This review summarises regulatory mechanisms governing dormant cancer cells entry and exit of dormancy, which may be used by PGCCs, and potential therapeutic strategies for targeting PGCCs.

14-3-3ε: a protein with complex physiology function but promising therapeutic potential in cancer.

Over the past decade, the role of the 14-3-3 protein has received increasing interest. Seven subtypes of 14-3-3 proteins exhibit high homology; however, each subtype maintains its specificity. The 14-3-3ε protein is involved in various physiological processes, including signal transduction, cell proliferation, apoptosis, autophagy, cell cycle regulation, repolarization of cardiac action, cardiac development, intracellular electrolyte homeostasis, neurodevelopment, and innate immunity. It also plays a significant role in the development and progression of various diseases, such as cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, and cancer. These immense and various involvements of 14-3-3ε in diverse processes makes it a promising target for drug development. Although extensive research has been conducted on 14-3-3 dimers, studies on 14-3-3 monomers are limited. This review aimed to provide an overview of recent reports on the molecular mechanisms involved in the regulation of binding partners by 14-3-3ε, focusing on issues that could help advance the frontiers of this field. Video Abstract.

Yucca schidigera purpurea-sourced arabinogalactan polysaccharides augments antioxidant capacity facilitating intestinal antioxidant functions.

This study isolated and purified a novel homogeneous arabinogalactan polysaccharide from Yucca schidigera extract (YSE), unveiled its unique structure and explored its antioxidant function. Firstly, the antioxidant potential of YSE was demonstrated in piglet trials. A homogeneous polysaccharide with a molecular weight of 24.2 kDa, designated as Yucca schidigera polysaccharide B (YPB), was isolated and purified from YSE. The monosaccharide composition of YPB was Rha, Araf, Galp, and Glcp, whose molar percentages were 2.8 %, 11.6 %, 45.5 %, and 40.0 %, respectively. Methylation analysis combined with 1D and 2D nuclear magnetic resonance showed that YPB was a complex polysaccharide with a main glycosidic linkage pattern of →2)-α-ʟ-Rha-(1 â†’ 3)-ß-ᴅ-Galp-(1→3)-ß-ᴅ-Galp-(1 â†’ 3)-ß-ᴅ-Galp-(1 â†’ 3)-ß-ᴅ-Glcp-(1→, and branched Araf and Galp fragments were connected with the main chain through →3,6)-ß-ᴅ-Galp-(1→, →3,4)-ß-ᴅ-Glcp-(1→, and →2,4)-α-ʟ-Rha-(1→ linkages. Following the in vitro biochemical assays of bioactive components, YPB should be the contributor to the antioxidant activity in YSE. Based on the establishment of oxidative stress model, YPB exhibited strong antioxidant capacity and activated NRF2 pathway, and then provided protection against the damage induced oxidative stress in IPEC-J2 cells and rats. Further analysis with inhibitors found that this antioxidant effect was attributed to its interaction with epidermal growth factor receptor and mannose receptor, and stimulating PI3K/AKT pathway.

Nomograms for predicting the overall and cancer-specific survival in patients with non-urothelial carcinoma of the bladder: A population-based study.

Non-urothelial carcinoma of the bladder (NUCB) is a relatively rare condition, with limited comprehensive studies conducted to date. This research aims to establish nomograms for forecasting overall survival (OS) and cancer-specific survival (CSS) in NUCB patients. It utilizes data of 2,522 patients from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2004 to 2015. The effectiveness of these nomograms was assessed using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Key independent predictors for OS included age, race, marital status, histological variants, grade, T stage, N stage, M stage, radical cystectomy and chemotherapy administration. For CSS, the predictors were similar, encompassing age, sex, marital status, histological variants, grade, T stage, N stage, M stage, radical cystectomy and chemotherapy. The nomograms showed strong predictive accuracy. In the training cohort, the area under the curve (AUC) values were 0.796 (OS) and 0.799 (CSS) at 1-year, 0.807 (OS) and 0.824 (CSS) at 3-year, and 0.807 (OS) and 0.827 (CSS) at 5-year intervals. In the validation cohort, AUC values were 0.798 (OS) and 0.798 (CSS) at 1-year, 0.810 (OS) and 0.826 (CSS) at 3-year, and 0.811 (OS) and 0.825 (CSS) at 5-year intervals, consistently around 0.8. Calibration curves indicated high congruence between predicted and actual probabilities of OS and CSS, while DCA demonstrated the models' substantial clinical utility. Overall, this study successfully developed and validated prognostic nomograms for NUCB, capable of accurately predicting OS and CSS at 1-, 3-, and 5-years, thereby offering valuable support in clinical decision-making and the design of clinical trials.

The Role of Cathepsin B in Pathophysiologies of Non-tumor and Tumor tissues: A Systematic Review.

Cathepsin B (CTSB), a lysosomal cysteine protease, plays an important role in human physiology and pathology. CTSB is associated with various human diseases, and its expression level and activity are closely related to disease progression and severity. Physiologically, CTSB is integrated into almost all lysosome-related processes, including protein turnover, degradation, and lysosome-mediated cell death. CTSB can lead to the development of various pathological processes through degradation and remodeling of the extracellular matrix. During tumor development and progression, CTSB has two opposing effects. Its pro-apoptotic properties reduce malignancy, while its proteolytic enzymatic activity promotes invasion and metastasis, thereby inducing malignancy. Here, we discuss the roles of CTSB in tumor and non-tumor disease pathophysiologies. We conclude that targeting the activity or expression of CTSB may be important for treating tumor and non-tumor diseases.

Zhiqiao Gancao Decoction Ameliorates Hyperalgesia in Lumbar Disc Herniation via the CCL2/CCR2 Signaling Pathway.

Purpose: The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism. Methods: The potential mechanism of ZQGCD's therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software. Results: Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream. Conclusion: The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression.

An m7G-related lncRNA signature predicts prognosis and reveals the immune microenvironment in bladder cancer.

Bladder cancer (BC) is a representative malignant tumor type, and the significance of N7-methyguanosine (m7G)-related lncRNAs in BC is still unclear. Utilizing m7G-related lncRNAs, we developed a prognostic model to evaluate BC's prognosis and tumor immunity. First, we selected prognostic lncRNAs related to m7G by co-expression analysis and univariate Cox regression and identified two clusters by consensus clustering. The two clusters differed significantly in terms of overall survival, clinicopathological factors, and immune microenvironment. Then, we further constructed a linear stepwise regression signature by multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Patients fell into high-risk (HR) and low-risk (LR) groups considering the train group risk score. HR group had worse prognoses when stratified by clinicopathological factors. The receiver operating curve (ROC) suggested that the signature had a better prognostic value. Tumor mutation burden (TMB) showed a negative relevance to the risk score, and patients with low TMB presented a better prognosis. Validation of the signature was carried out with multivariate and univariate Cox regression analysis, nomogram, principal component analysis (PCA), C-Index, and quantitative reverse transcriptase PCR (qRT-PCR). Finally, the gene set enrichment analysis (GSEA) demonstrated the enrichment of tumor-related pathways in HR groups, and single-sample gene set enrichment analysis (ssGSEA) indicated a close association of risk score with tumor immunity. According to the drug sensitivity test, the signature could predict the effects of conventional chemotherapy drugs. In conclusion, our study indicates the close relevance of m7G-related lncRNAs to BC, and the established risk signature can effectively evaluate patient prognosis and tumor immunity and is expected to become a novel prognostic marker for BC patients.

Early life exposure to chronic unpredictable stress induces anxiety-like behaviors and increases the excitability of cerebellar neurons in zebrafish.

Anxiety is a common emotional disorder in children. To understand its underlying mechanisms, chronic unpredictable stress (CUS) has been established as a stress model in zebrafish. By using the tall tank test, the stress response reliability could be improved in adult fish which has not been confirmed in larvae. In addition, the increasing evidences have shown that cerebellum plays important roles in anxiety. Whether CUS will affect cerebellar neuronal activity remains unknown. We found that CUS exposure to larvae (from 10 to 17 days post fertilization) induced anxiety-like behaviors and social cohesion impairments within 1-2 d after CUS, including a prolonged freezing time, an increased time spent at the bottom of tank, an increased thigmotaxis index, and an increased interindividual distance. Our results showed that the four behavioral tests were homogeneous, especially the tall tank test either anxiety-like behaviors or the basal locomotion. Furthermore, we found that CUS enhanced the excitability of cerebellar neurons, as the amplitude, frequency, time to peak and half-width of spontaneous firing significantly decreased, as well as the amplitude of excitatory post-synaptic current when compared with the control group. CUS also activated hyperpolarization-activated cyclic nucleotide-gated and potassium channels of cerebellar neurons. Multiple linear regression analysis showed that the total distance in bottom (tall tank test) was correlated positively with outward Na+-K+ currents (r = 0.848, P = 0.016), and the thigmotaxis index (open field test) correlated with action potential amplitude (r = 0.854, P = 0.030). Altogether, early life CUS transiently induced an anxiety-like behavior which could be more accurately assessed by combining the tall tank test with other behavior tests in young zebrafish. CUS increased the excitability of cerebellar neurons might provide new targets to treat emotional diseases such as anxiety.

High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol.

Background: Hypoxia-inducible factor 1-alpha (HIF-1α) is overexpressed in pancreatic ductal adenocarcinomas (PDACs). However, the prognosis of high expression of HIF-1α in PDACs remains controversial because of lacking a solid support. A meta-analysis may help for a better understanding of the role of HIF-1α in the prognosis of PDACs. Methods: By using a systematic approach, we conducted a meta-analysis from current literature. We performed an advanced search in PubMed, Embase, Cochrane Library and Web of Science databases. Recorded studies were published between September 1, 2001, and February 26, 2021, in English and related to the expression of HIF-1α in PDAC. We pooled and combined hazard ratios (HRs) and 95% confidence intervals (CIs) to show the effect of HIF-1α expression on overall survival (OS). We pooled also risk ratios (RRs) and 95% CIs to assess the correlation between HIF-1α expression and clinicopathological characteristics in PDAC. We evaluated publication bias among included studies through the Begg's test and Egger's test. From "Expression Plots" modules in the Gene Expression Profiling Interactive Analysis (GEPIA) database, we showed the difference of mRNA level for HIF1A between 179 pancreatic adenocarcinomas (PAADs) and 171 normal pancreatic tissues. Results: This meta-analysis included 11 studies and 764 patients. High expression of HIF-1α was associated with shorter OS compared to low HIF-1α expression in PDAC (HR =1.74, 95% CI: 1.49-2.04, P<0.001). Patients with high expression of HIF-1α tended to have an increased risk of earlier lymph node metastasis (LNM) (RR =1.63, 95% CI: 1.36-1.95, P<0.001), and more advanced clinical stage (RR =1.64, 95% CI: 1.38-1.97, P<0.001) compared to those with low HIF-1α expression. Expression plots from GEPIA database showed HIF1A overexpressed in PDAC tissues compared to normal tissues (Log2FC =2, P<0.01). Conclusions: High HIF-1α expression associated with worse prognosis of PDACs compared to low HIF-1α expression. Since HIF-1α expression is greater in PDAC than normal pancreas, it could serve as a prognostic factor and potential therapeutic target. However, due to the complex role of HIF-1α in physiology and pathology, therapeutic intervention should be considered with caution.

Ecological risk and health risk analysis of soil potentially toxic elements from oil production plants in central China.

In this study, the enrichment factor (EF) and pollution load index (PLI) were used to evaluate the pollution of potential toxic elements (PTEs) in the soil near the oil production plants in central China, and the potential ecological risk (PER) and human health risk (HHR) assessment model were used to evaluate the PER and HHR caused by the soil PTEs in the study area. The mean EFs of all PTEs were greater than 1, PTEs have accumulated to varying degrees, especially Cr, Ni and Pb were the most serious. The average value of PLI was 2.62, indicating that the soil PTEs were seriously polluted. The average [Formula: see text] values of PTEs were Cr > Pb > Cd > Ni > As > Cu > Zn > Mn, of which Cr, Pb, Cd and Ni were at medium and above PER levels. Both adults and children in the study area suffered from varying degrees of non-carcinogenic and carcinogenic risks. The total hazard index (THI) values of children (7.31) and adults (1.03) were all > 1, and the total carcinogenic risk index (TCRI) of children (9.44E-04) and adults (5.75E-04) were also > 10-4. In particular, the hazardous quotient (HQ) of Cr and Pb for children under the oral intake route were 4.91 and 1.17, respectively, caused serious non-carcinogenic risk. And the carcinogenic risk index (CRI) values of the PTEs in adults and children under the three exposure routes were Cr > Ni > > As > Pb > > Cd. Among them, the CRI values of Cr and Ni in children and adults by oral intake were both greater than 10-4, showing a strong carcinogenic risk. The results will provide scientific basis for environmental protection and population health protection in this area.

Circulating malondialdehyde level in patients with epilepsy: A meta-analysis.

PURPOSE: Malondialdehyde (MDA) is an oxidative stress marker that determines the impact of oxidation on MDA levels in patients with epilepsy (PWE) and healthy controls. METHODS: A meta-analysis was performed on 15 published studies. A total of 559 PWE and 853 healthy controls were included to evaluate the MDA levels in erythrocytes, serum, and plasma, respectively. RESULTS: Meta-analysis showed that MDA levels were significantly higher in PWE than in healthy controls. Moreover, the meta-analysis demonstrated that MDA levels were increased in three subgroups of serum, plasma, and red blood cells from epileptic patients compared with the control group. Differentiating the subgroups according to the proportion of female patients, region, and MDA detection method showed that MDA levels in epileptic patients were higher than in healthy controls. In addition, MDA levels were significantly higher in the Asian subgroup than in the non-Asian subgroup. There was no potential publication bias. The age of the patients, the proportion of female patients, the region, and methods for measuring MDA of the included studies did not cause heterogeneity. CONCLUSION: Our results showed increased MDA levels in erythrocytes, serum, and plasma in PWE, which may be an indicator of oxidative damage in epilepsy. This is the first meta-analysis of circulating MDA levels in PWE and healthy controls.

[Bladder wall neourethra technique improves early urinary continence after laparoscopic radical prostatectomy].

OBJECTIVE: To study the effect of the bladder wall neourethra (BWN) technique on early urinary continence after laparoscopic radical prostatectomy (LRP). METHODS: We prospectively selected 40 cases of LRP performed in our hospital from August 2020 to August 2021 and randomly divided them into a BWN group (n = 20) and a control group (n = 20). We recorded the urinary continence rate of the two groups of patients at 7, 30, 90 and 180 days, and measured the maximum urethral pressure (MUP), functional urethral length (FUL) and functional urethral area (UFA) and observed the shape of the neourethra closure by MRI at 1 month after catheter removal. RESULTS: The urinary continence rates were significantly higher in the BWN than in the control group at 7 days (90.0% vs 25.0%, P < 0.001), 30 days (95.0% vs 35.0%, P < 0.001), 90 days (100% vs 60.0%, P < 0.05) and 180 days (100% vs 90.0%, P > 0.05) after catheter removal. No statistically significant difference was observed in MUP between the two groups (P > 0.05). FUL and FUA were remarkably higher in the BWN than in the control group (P < 0.01). MRI showed tight closure of the neourethra in the BWN group in the urine storage period. CONCLUSION: The BWN technique can significantly prolong FUL and improve early urinary continence after LRP.

Poly(I:C)-exposed zebrafish shows autism-like behaviors which are ameliorated by fabp2 gene knockout.

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly representing impaired social communication. The etiology of ASD includes genetic and environmental risk factors. Rodent models containing ASD risk gene mutations or environmental risk factors, such as exposure to maternal inflammation, show abnormal behavior. Although zebrafish conserves many important brain structures of humans and has sophisticated and fine behaviors in social interaction, it is unknown whether the social behaviors of their offspring would be impaired due to exposure to maternal inflammation. Methods: We exposed zebrafish to maternal immune activation (MIA) by injection with polyinosinic:polycytidylic acid [poly(I:C)], and screened their behaviors through social behavioral tests such as social preference and shoaling behavior tests. We compared phenotypes resulted from different ways of poly(I:C) exposure. RNA sequencing was performed to explore the differential expression genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis was performed with the detected DEGs to find the concentrated pathways. Finally, we knocked out the fatty acid-binding protein 2 (fabp2), a key node of the concentrated PPI network, to find its rescues on the altered social behavior. Results: We reported here that MIA offspring born to mothers injected with poly(I:C) exhibited impaired social approach and social cohesion that mimicked human ASD phenotypes. Both maternal exposure and direct embryo exposure to poly(I:C) resulted in activations of the innate immune system through toll-like receptors 3 and 4. RNA-sequencing results from MIA brain tissues illustrated that the numbers of overexpressed genes were significantly more than that of underexpressed genes. GO and KEGG analyses found that MIA-induced DEGs were mainly concentrated in complement and coagulation cascade pathways. PPI network analyses suggested that villin-1 (vil1) pathway might play a key role in MIA-induced ASD. Knockout of fabp2 in F0 zebrafish rescued the social behavior deficits in MIA offspring. Conclusions: Overall, our work established an ASD model with assessable behavior phenotype in zebrafish and provided key insights into environmental risk factor in ASD etiology and the influence of fabp2 gene on ASD-like behavior.

miR-485's anti-drug resistant epilepsy effects by regulating SV2A/PSD-95 and targeting ABCC1 and neuronal signaling-transduction proteins in hippocampus of rats.

AIM: Drug-resistant epilepsy (DRE), most subsequently developing refractory epilepsy, causes a significant burden to the society. microRNAs have been demonstrated as key regulators and therapeutic targets in epilepsy. Accordingly, the aim of the present study was to test whether miR-485 could be a potential target for DRE. METHODS AND RESULTS: An in vivo DRE model was developed in Sprague-Dawley rats by lithium chloride-pilocarpine and screened by antiepileptic drugs. We found that miR-485-5p in hippocampus was significant downregulated at early stage and recovered to normal level at late stage of DRE. Overexpression of miR-485-5p in dentate gyrus (DG) of hippocampus in DRE rats could significantly decrease the frequency of seizures and the numbers of epileptiform spikes of hippocampal DG neuron, and could specifically decrease SV2A expression without affecting PSD-95 expression in DG. Furthermore, miR-485-5p overexpression could significantly downregulate the expression of efflux transporter related to multidrug resistance (ABCC1) in hippocampus at late stage of DRE. Finally, a specific expression pattern of neuronal signaling-transduction proteins (LRP4, MDM4, p53, and TMBIM1) for DRE was observed, and miR-485-5p overexpression could modulate these proteins' expression levels toward normal in hippocampus both at early and late stage of DRE. CONCLUSION: Collectively, these results suggest that miR-485 was a potential target for anti-DRE, and this effects might be partially via miR-485-5p/homeostatic-synaptic plasticity-molecule axis and/or targeting efflux transporter (ABCC1) and other neuronal signaling-transduction proteins (LRP4, MDM4, p53, and TMBIM1).

Application of Three-dimensional Visualization Fused with Ultrasound for Percutaneous Renal Puncture.

We present here the three-dimensional (3D) visualization fused with ultrasound and to evaluate its clinical application effect preliminarily. One hundred and eighteen patients with renal calculi in our hospital from September 2017 to December 2019 were prospectively randomized into two groups. The experimental group was treated with percutaneous renal puncture guided by the 3D visualization fused with ultrasound. The control group was treated with percutaneous renal puncture guided by B-ultrasonography (B-US). The puncture time in the experimental versus control group was 4.36 ± 1.28 min versus 10.72 ± 2.94 min (P = 0.000), operation time was 65.85 ± 10.63 min versus 81.34 ± 12.52 min (P = 0.000), and the loss of hemoglobin was 8.55 ± 3.76 g/L min versus 13.33 ± 5.81 g/L(P = 0.000), and the success rate of establishing the channel at one time was 98.41% versus 81.82% (P = 0.002), and the coincidence rate between the channel and the longitudinal axis of the target renal calyx was 88.89% versus 60.00% (P = 0.000). The 3D visualization fused with ultrasound could guide precise puncture to target calyces, reduce operation time, bleeding, and difficulty of puncture.

Demethoxycucumin protects MDA-MB-231 cells induced bone destruction through JNK and ERK pathways inhibition.

Bone is the most common late metastasis of breast cancer. Bone metastasis causes not only severe bone pain, but also bone-related diseases such as pathological fractures, which are closely related to osteoclasts. The effects of demethoxycurcumin (DMC) on osteoclast biology has not been investigated. In this study, we explored the effects of DMC on MDA-MB-231 cells, MCF-7 cells, and osteoclasts induced by RANKL in vitro, as well as the protective effect on bone destruction of tumor bone metastasis in vivo. DMC showed inhibitory effect on the migration and promotes the apoptosis of MDA-MB-231 and MCF-7 cells. At the same time, DMC inhibited osteoclast maturation and mature osteoclast bone resorption in a dose-dependent manner, and suppressed the expression of osteoclast marker genes TRAP, CTSK, MMP9, V-ATPase-d2 and DC-STAMP significantly. Biochemical data showed that DMC inhibited tumor cells and osteoclasts by inhibiting the early activation of ERK and JNK MAPK pathway. Consistent with the results in vitro, we confirmed that DMC protects bone destruction caused by tumor metastasis in vivo. In short, our study confirmed that DMC could be used as a potential drug for the treatment of tumor bone destruction.

Transversus Abdominis Plane Block With Liposomal Bupivacaine vs. Regular Anesthetics for Pain Control After Surgery: A Systematic Review and Meta-Analysis.

Background: Transverse abdominal plane (TAP) blocks are used to provide pain relief after abdominopelvic surgeries. The role of liposomal bupivacaine (LB) for TAP blocks is unclear. Therefore, this study aimed to synthesize evidence on the efficacy of LB vs. regular anesthetics in improving outcomes of TAP block. Methods: PubMed, Science Direct, Embase, Springer, and CENTRAL databases were searched up to July 24, 2020. Studies comparing LB with any regular anesthetic for TAP block for any surgical procedure and reporting total analgesic consumption (TAC) or pain scores were included. Results: Seven studies including five randomized controlled trials (RCTs) were reviewed. LB was compared with regular bupivacaine (RB) in all studies. A descriptive analysis was conducted for TAC due to heterogeneity in data presentation. There were variations in the outcomes of studies reporting TAC. Meta-analysis of pain scores indicated statistically significant reduction of pain with the use of LB at 12 h (MD: -0.89 95% CI: -1.44, -0.34 I2 = 0% p = 0.01), 24 h (MD: -0.64 95% CI: -1.21, -0.06 I2 = 0% p = 0.03), 48 h (MD: -0.40 95% CI: -0.77, 0.04 I2 = 0% p = 0.03) but not at 72 h (MD: -0.37 95% CI: -1.31, 0.56 I2 = 57% p = 0.43). Pooled analysis indicated no difference in the duration of hospital stay between LB and RB (MD: -0.18 95% CI: -0.49, 0.14 I2 = 61% p = 0.27). LB significantly reduced the number of days to first ambulation postsurgery (MD: -0.28 95% CI: -0.50, -0.06 I2 = 0% p = 0.01). Conclusions: Current evidence on the role of LB for providing prolonged analgesia with TAP blocks is unclear. Conflicting results have been reported for TAC. LB may result in a small reduction in pain scores up to 48 h but not at 72 h. Further, high-quality homogenous RCTs are needed to establish high-quality evidence.

Metastasis-associated protein 1 (MTA1) regulates the catecholamine production homeostasis via transcriptional repression of aromatic l-amino acid decarboxylase (Aadc) in the interstitial cells of Cajal of mouse prostate.

Based on the lately identified role for the interstitial cells of Cajal (ICCs) of mouse prostate in catecholamine production, as well as the well-established role for the master coregulator metastasis-associated protein 1 (MTA1) in inflammation, we probed into the functional link between aberrant MTA1 expression and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using both a MTA1-/- mouse model of experimental autoimmune prostatitis (EAP) and an in vitro chronic prostatitis model in cultured murine ICCs. EAP-induced MTA1 expression was enriched in ICCs of mouse prostate. EAP resulted in a higher increase in the pelvic pain response in MTA1-/- mice compared to WT mice. Consistently, the ICCs from MTA1-/- mice produced higher levels of catecholamines upon induction of in vitro chronic prostatitis. Mechanistically, MTA1 could directly suppress the transcription of Aadc, a rate-limiting enzyme during catecholamine synthesis, in a HDAC2-depdendent manner. Importantly, treatment with AADC inhibitor NSD-1015 significantly ameliorated EAP-elicited pain response and catecholamine overactivity in MTA1-/- mice. Taken together, our findings reveal an inherent regulatory role of the MTA1/AADC pathway in the maintenance of catecholamine production homeostasis in prostate ICCs, and also point to a potential use of HDAC inhibitors and/or AADC inhibitors to treat CP/CPPS.

Icariin controlled release on a silk fibroin/mesoporous bioactive glass nanoparticles scaffold for promoting stem cell osteogenic differentiation.

The treatment of bone defects caused by various reasons is still a major problem in orthopedic clinical work. Many studies on osteogenic implant materials have used various biologically active factors such as osteogenic inducers, but these biologically active factors have various side effects. Therefore, in this study, silk fibroin (SF) was used as a scaffold material, mesoporous bioactive glass nanoparticles (MBGNs) as a sustained release carrier, and the traditional Chinese drug icariin (ICA) was loaded to promote bone formation. The experiments in this study have proven that SF/MBGNs-ICA scaffolds can successfully load and release ICA for a long time, and the sustained-release ICA can promote the proliferation and differentiation of BMSCs for a long time. This controlled-release ICA organic/inorganic two-component scaffold material is expected to become a new bone grafting solution.