Fibrostricturing Crohn's disease is marked by an increase in active eosinophils in the deeper layers.

INTRODUCTION: Approximately 50% of Crohn's disease (CD) patients develop intestinal strictures necessitating surgery. The immune cell distribution in these strictures remains uncharacterized. We aimed to identify the immune cells in intestinal strictures of CD patients. METHODS: During ileocolonic resections, transmural sections of terminal ileum were sampled from 25 CD patients and 10 non-inflammatory bowel disease (IBD) controls. Macroscopically, unaffected, fibrostenotic and inflamed ileum was collected and analysed for immune cell distribution (flow cytometry) and protein expression. Collagen deposition was assessed via a Masson's Trichrome staining. Eosinophil and fibroblast co-localization was assessed through immunohistochemistry. RESULTS: The Masson's Trichrome staining confirmed augmented collagen deposition in both the fibrotic as the inflamed region, though with a significant increased collagen deposition in fibrotic compared to inflamed tissue. Distinct Th1, Th2, regulatory T cells, dendritic cells and monocytes were identified in fibrotic and inflamed CD ileum compared to unaffected ileum of CD patients as non-IBD controls. Only minor differences were observed between fibrotic and inflamed tissue, with more active eosinophils in fibrotic deeper layers and increased Eosinophil Cationic Protein (ECP) protein expression in inflamed deeper layers. Lastly, no differences in eosinophil and fibroblast co-localization was observed between the different regions. CONCLUSION: This study characterized immune cell distribution and protein expression in fibrotic and inflamed ileal tissue of CD patients. Immunologic, proteomic and histological data suggest inflammation and fibrosis are intertwined, with large overlap between both tissue types. However strikingly, we did identify an increased presence of active eosinophils only in the fibrotic deeper layers, suggesting their potential role in fibrosis development.

Postponement of total knee arthroplasties due to pandemic causes significant deterioration on patients' preoperative knee and quality of life scores.

Introduction: Elective surgeries were postponed during the COVID-19 pandemic to alleviate healthcare strains, affecting majority of elective orthopaedic surgeries such as total knee arthroplasties (TKAs). The aim of this study is to evaluate the impact on knee function and quality of life of patients who had their planned TKA postponed due to the pandemic. Methods: This is a retrospective analysis of data collected in a tertiary hospital. Patients included were diagnosed with primary knee osteoarthritis and they were initially scheduled for primary TKA between January to April 2020 but surgery was postponed by at least 6 months from the initial operative date. 160 patients were included in this study (53 males and 107 females, mean age 68.0 ± 8.1). Patients were assessed prior to initial surgery date and assessed again, prior to the postponed surgery date. Clinical scores included Knee Society Function Score (KSFS), Knee Society Knee Score (KSKS), Oxford Knee scores (OKS) and Short-Form 36 Physical and Mental Component Scores. (SF36 PCS and MCS). Paired T-test was performed for parametric data whereas Wilcoxon signed-rank analysis was performed for non-parametric data. Results: Comparing initial preoperative versus postponement preoperative scores, the cohort had significantly poorer KSKS (38.4 ± 15.4 and 36.5 ± 15.4, p = 0.034), SF36 PCS (34.3 ± 9.2 and 32.7 ± 8.6, p = 0.02) and OKS (34.9 ± 0.77 and 35.8 ± 8.6, p = 0.02) scores respectively. Conclusion: The postponement of elective TKAs has resulted in a significant deterioration of knee scores and physical quality of live scores of patients in a short span of 6 months. Further studies can evaluate if there are repercussions on long term TKAs outcomes. Level of evidence: Retrospective study, Level III.

One-Step Electrochemical Ethylene-to-Ethylene Glycol Conversion over a Multitasking Molecular Catalyst.

Ethylene glycol is an essential commodity chemical with high demand, which is conventionally produced via thermocatalytic oxidation of ethylene with huge fossil fuel consumption and CO2 emission. The one-step electrochemical approach offers a sustainable route but suffers from reliance on noble metal catalysts, low activity, and mediocre selectivity. Herein, we report a one-step electrochemical oxidation of ethylene to ethylene glycol over an earth-abundant metal-based molecular catalyst, a cobalt phthalocyanine supported on a carbon nanotube (CoPc/CNT). The catalyst delivers ethylene glycol with 100% selectivity and 1.78 min-1 turnover frequency at room temperature and ambient pressure, more competitive than those obtained over palladium catalysts. Experimental data demonstrate that the catalyst orchestrates multiple tasks in sequence, involving electrochemical water activation to generate high-valence Co-oxo species, ethylene epoxidation to afford an ethylene oxide intermediate via oxygen transfer, and eventually ring-opening of ethylene oxide to ethylene glycol facilitated by in situ formed Lewis acid site. This work offers a great opportunity for commodity chemicals synthesis based on a one-step, earth-abundant metal-catalyzed, and renewable electricity-driven route.

Single and combined effects of increased temperature and methylmercury on different stages of the marine rotifer Brachionus plicatilis.

Rapid, anthropogenic activity-induced global warming is a severe problem that not only raises water temperatures but also shifts aquatic environments by increasing the bioavailability of heavy metals (HMs), with potentially complicated effects on aquatic organisms, including small aquatic invertebrates. For this paper, we investigated the combined effects of temperature (23 and 28 °C) and methylmercury (MeHg) by measuring physiological changes, bioaccumulation, oxidative stress, antioxidants, and the mitogen-activated protein kinase signaling pathway in the marine rotifer Brachionus plicatilis. High temperature and MeHg adversely affected the survival rate, lifespan, and population of rotifers, and bioaccumulation, oxidative stress, and biochemical reactions depended on the developmental stage, with neonates showing higher susceptibility than adults. These findings demonstrate that increased temperature enhances potentially toxic effects from MeHg, and susceptibility differs with the developmental stage. This study provides a comprehensive understanding of the combined effects of elevated temperature and MeHg on rotifers. ENVIRONMENTAL IMPLICATION: Methylmercury (MeHg) is a widespread and harmful heavy metal that can induce lethal effects on aquatic organisms in even trace amounts. The toxicity of metals can vary depending on various environmental conditions. In particular, rising temperatures are considered a major factor affecting bioavailability and toxicity by changing the sensitivity of organisms. However, there are few studies on the combinational effects of high temperatures and MeHg on aquatic animals, especially invertebrates. Our research would contribute to understanding the actual responses of aquatic organisms to complex aquatic environments.

Spatiotemporal profile and ecological impacts of major and trace elements in surface sediments of marginal seas of the Arctic and Northern Pacific Oceans.

The status and ecological impacts of sedimentary elements of the marginal seas of Arctic and Northern Pacific Oceans was investigated during 2016 to 2018 by using inductively coupled plasma mass spectrometry. Industrial (0.006 mg kg-1-64.6 g kg-1), precious (0.003-43.8 mg kg-1), rare earth (0.006-112.9 mg kg-1), and heavy metal (0.009-398.9 mg kg-1) elements showed spatial variation, and temporal uniformity. The results indicated ΣREEs and light REEs enrichment compared to chondrite and heavy REEs, respectively, while nonsignificant positive and negative δCe and δEu anomalies existed, respectively. High contamination and extreme enrichment of priority control, industrial (As, Mo, Re, Sb), precious (Au, Ir, Pd, Pt, and Ru) and RE elements indicated potential moderate to high ecological and biological risks. The study highlighted the ecological importance and fragile nature of these ecosystems and calls for an urgent action to ensure sustainability of these ecosystems.

Overexpression of sirtuin 1 attenuates calcium oxalate-induced kidney injury by promoting macrophage polarization.

Sirtuin 1 (SIRT1) protein is involved in macrophage differentiation, while NOTCH signaling affects inflammation and macrophage polarization. Inflammation and macrophage infiltration are typical processes that accompany kidney stone formation. However, the role and mechanism of SIRT1 in renal tubular epithelial cell injury caused by calcium oxalate (CaOx) deposition and the relationship between SIRT1 and the NOTCH signaling pathway in this urological disorder are unclear. This study investigated whether SIRT1 promotes macrophage polarization to inhibit CaOx crystal deposition and reduce renal tubular epithelial cell injury. Public single-cell sequencing data, RT-qPCR, immunostaining approaches, and Western blotting showed decreased SIRT1 expression in macrophages treated with CaOx or exposed to kidney stones. Macrophages overexpressing SIRT1 differentiated towards the anti-inflammatory M2 phenotype, significantly inhibiting apoptosis and alleviating injury in the kidneys of mice with hyperoxaluria. Conversely, decreased SIRT1 expression in CaOx-treated macrophages triggered Notch signaling pathway activation, promoting macrophage polarization towards the pro-inflammatory M1 phenotype. Our results suggest that SIRT1 promotes macrophage polarization towards the M2 phenotype by repressing the NOTCH signaling pathway, which reduces CaOx crystal deposition, apoptosis, and damage in the kidney. Therefore, we propose SIRT1 as a potential target for preventing disease progression in patients with kidney stones.

Unveiling the unprecedented catalytic capability of micro-sized Co-ZIF-L for the thermal decomposition of RDX by 2D-structure-induced mechanism reversal.

Developing MOF-based catalysts with superior catalytic properties for the thermal decomposition of cyclotrimethylenetrinitramine (RDX) is significant for the application of novel and efficient combustion catalysts oriented to RDX-based propellants with excellent combustion performance. Herein, micro-sized Co-ZIF-L with a star-like morphology (SL-Co-ZIF-L) was found to exhibit unprecedented catalytic capability for the decomposition of RDX, which can lower the decomposition temperature of RDX by 42.9 °C and boost the heat release by 50.8%, superior to that of all the ever-reported MOFs and even ZIF-67, which has similar chemical composition but a much smaller size. In-depth mechanism study from both experimental and theoretical views reveals that the weekly interacted 2D layered structure of SL-Co-ZIF-L could activate the exothermic C-N fission pathway for the decomposition of RDX in the condensed phase, thus reversing the commonly advantageous N-N fission pathway and promoting the decomposition process in the low-temperature stage. Our study reveals the unusually superior catalytic capability of micro-sized MOF catalysts and sheds light on the rational structure design of catalysts used in micromolecule transformation reactions, typically the thermal decomposition of energetic materials.

Koumine alleviates rheumatoid arthritis by regulating macrophage polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: The imbalance between M1-and M2-polarized macrophages is one of the major pathophysiological changes in RA. Therefore, targeted macrophage polarization may be an effective therapy for RA. Koumine, an alkaloid monomer with the highest content and low toxicity in Gelsemium elegans Benth., has the effect of treating RA by playing an immunomodulatory role by influencing various immune cells. However, whether koumine affects macrophage polarization in RA and the associated molecular mechanisms remain unknown. AIM OF THE STUDY: To investigate the mechanism of the anti-RA effect of koumine on macrophage polarization. MATERIALS AND METHODS: The effect of koumine on macrophage polarization was investigated in vivo and in vitro. We first explored the effects of koumine on AIA rats and detected the levels of M1/M2 macrophage polarization markers in the spleen by western blotting. Then, we explored the regulatory effect of koumine on M1/M2 macrophage polarization and the effect on the PI3K/AKT signaling pathway in vitro. Finally, we verified the effects of koumine on macrophage polarization in CIA mice. RESULTS: We found that koumine alleviated symptoms, including relieving pain, reducing joint redness and swelling in AIA rats and restoring the M1/M2 macrophage balance in vivo. Interestingly, koumine had an inhibitory effect on both M1 and M2 macrophage polarization in vitro, but it had a stronger inhibitory effect on M1 macrophage. In a mixed polarization experiment, koumine mainly inhibited M1 macrophage polarization and had an inhibitory effect on the PI3K/AKT signaling pathway. Finally, we found that koumine had therapeutic effects on CIA mice, regulated macrophage polarization and inhibited the PI3K/AKT signaling pathway. CONCLUSIONS: Our results reveal that koumine regulates macrophage polarization through the PI3K/AKT signaling pathway. This may be one of the important mechanisms of its anti-RA effect, which provides a theoretical and scientific basis for the possible clinical application of koumine.

A Longer Duration of Myelopathy Symptoms is Associated With the Lack of Intraoperative Motor Evoked Potential Improvement During Decompressive Cervical Myelopathy Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: We aim to investigate the relationship between the intraoperative motor evoked potential (MEP) signal changes during surgical treatment of cervical myelopathy with postoperative functional outcomes and determine what factors correlate with MEP signal changes. SUMMARY OF BACKGROUND DATA: Intraoperative neurophysiologic monitoring with MEP for cervical cord decompression can potentially predict postoperative neurological complications. MATERIALS AND METHODS: We prospectively collected data from 114 consecutive cervical compressive myelopathy patients who underwent decompressive cervical spine surgery. Functional outcomes were measured preoperatively and postoperatively at the 6-month mark, using the modified Japanese Orthopedic Association score. RESULTS: Among the 114 patients, 87 patients showed significant MEP improvement, 1 patient with MEP degeneration, 3 patients with no change in MEP, and 23 patients with MEP change, but which eventually returned to baseline. Univariate analysis showed that patients with MEP improvement had similar 6-month functional and Japanese Orthopedic Association scores compared with patients who did not have MEP improvement. Critically, a longer duration of symptoms was shown to have a statistically significant relationship with patients who did not have MEP improvement on univariate analysis (49.2 wk in patients with no MEP improvement compared with 34.59 wk in patients with MEP improvement, P = 0.03) but this did not translate to differences in functional outcomes. There was also no statistically significant association between the functional outcome scores and demographics, surgical, or radiologic factors. CONCLUSIONS: Our study shows that the duration of symptoms is not attributed to lower functional outcomes but is associated with a lack of MEP improvement. LEVEL OF EVIDENCE: Level III.

[Ameliorative Effects of Cang-ai Volatile Oil on Left Ventricular Remodeling in Rats].

Objective: To evaluate with 7T cardiac magnetic resonance tissue tracking imaging (CMR-TT) the ameliorative effect of Cang-ai volatile oil (CAVO) on left ventricular remodeling (LVR) in rats induced by isoproterenol (ISO), and to make preliminary investigation into CAVO's effects on endothelial dysfunction in LVR. Methods: A total of 35 healthy male Sprague-Dawley (SD) rats were randomly assigned to two groups, the experimental group ( n=27) and the normal control group ( n=8). The rat model of LVR was established by subcutaneous injection of ISO solution at 10 mg·kg -1·d -1 at multiple sites for 10 consecutive days. After modeling was completed, the surviving rats ( n=24) in the experimental group were then randomly assigned to the blank experimental group, CAVO group, and Shexiang Baoxin pill (SXBXP) group ( n=8 in each group). Rats in each group were given via gavage the corresponding intervention medicine or an equivalent amount of normal saline solution for 28 consecutive days. At the end of modeling and intragastric intervention, 7T CMR cine sequence scanning was conducted to collect data. Then, post-processing software CVI42 was used to analyze the images and to compare and contrast the changes in the parameters of left ventricular cardiac function and myocardial strain in each group before and after the administration of the medication. The rats were sacrificed after MRI scanning, and their hearts were harvested for pathological examination. The levels of serum biochemical indicators were measured by enzyme-linked immunosorbent assay (ELISA). Results: CAVO significantly increased LV ejection fraction and overall myocardial strain parameters in LVR rats, while it decreased LV volume, mass, and serum levels of endothelial function indicators in LVR rats. In addition, pathological staining showed marked improvements in the hypertrophy, necrosis and interstitial fibrosis of cardiomyocytes. Conclusion: Through the regulation of myocardial vascular endothelial function, CAVO can significantly improve cardiac functions in LVR rats, delay the process of ventricular remodeling, and have a certain amount of protective effect on cardiac structure and function in rats.

First evidence of meso- and microplastics on the mangrove leaves ingested by herbivorous snails and induced transcriptional responses.

Although evidence suggests the ubiquity of meso- and microplastics (MMPs) in mangrove forests, our knowledge of their bioavailability and risk on mangrove leaves is scarce. Here, we investigated MMP contamination concerning submerged mangrove leaves and herbivorous snails that mainly feed on them from the four mangrove forests located in Beibu Gulf, Guangxi Province, China. Results showed that the MMP abundance on the mangrove leaves ranged from 0.01 ± 0.00 to 0.42 ± 0.15 items cm-2, while it ranged from 0.33 ± 0.21 to 6.20 ± 2.91 items individual-1 in the snails. There were significant positive correlations between snails and leaves regarding the abundance of total MMPs and the proportions of MMPs with the same characteristics. Expanded polystyrene (EPS) that mainly derived from aquaculture rafts, accounted for a major component both on the leaves and in the snails in Shi Jiao (SJ). Both the detection frequency and percentage of larger EPS (2.00-17.50 mm) on the leaves in SJ were higher than other sites. Meanwhile, the detection frequency, abundance and percentage of larger EPS on the leaves had significant positive correlations with those of micro-EPS in the snails. These findings suggested that mangrove leaves may represent a viable pathway for MMPs to enter the herbivorous snails. Larger EPS with higher frequency of occurrence on mangrove leaves were more likely to be encountered and ingested by snail considering its opportunistic feeding behavior. In addition, 11 sensitive genes involved in the processes of metabolism, intestinal mucosal immune systems, and cellular transduction in the snails were significantly suppressed by MMP exposure, which may be potentially used as early biomarkers to indicate the biological effects of MMPs under realistic environmental conditions. Overall, this study provides novel insights into the fate, sources, and biological effects of MMPs on mangrove leaves.

Basolateral amygdala astrocytes modulate diabetic neuropathic pain and may be a potential therapeutic target for koumine.

BACKGROUND AND PURPOSE: New remedies are required for the treatment of diabetic neuropathic pain (DNP) due to insufficient efficacy of available therapies. Here, we used chemogenetic approaches combined with in vivo pharmacology to elucidate the role of basolateral amygdala (BLA) astrocytes in DNP pathogenesis and provide new insights into therapeutic strategies for DNP. EXPERIMENTAL APPROACH: A streptozotocin-induced DNP model was established. Designer receptors exclusively activated by designer drugs (DREADDs) were used to regulate astrocyte activity. Mechanical hyperalgesia was assessed using the electronic von Frey test. Anxiety-like behaviours were detected using open field and elevated plus maze tests. Astrocytic activity was detected by immunofluorescence, and cytokine content was determined by ELISA. KEY RESULTS: BLA astrocytes were regulated by DREADDs, and inhibition of BLA astrocytes attenuated mechanical allodynia and pain-related negative emotions in DNP rats. In contrast, temporary activation of BLA astrocytes induced allodynia without anxious behaviours in naive rats. In addition, koumine (KM) alleviated mechanical allodynia and anxiety-like behaviours in DNP rats, inhibited the activation of BLA astrocytes and suppressed the inflammatory response. Furthermore, persistent activation of BLA astrocytes through chemogenetics mimicked chronic pain, and KM alleviated the pain hypersensitivity and anxiety-like behaviours. CONCLUSION AND IMPLICATIONS: DREADDs bidirectionally regulate the activity of BLA astrocytes, which proves for the first time the role of BLA astrocyte activation in the pathogenesis of DNP and represents a novel therapeutic strategy for DNP. KM ameliorates DNP, perhaps by inhibiting the activation of BLA astrocytes and reveal KM as a potential candidate for treating DNP.

Regulation effect of koumine on T-helper cell polarization in rheumatoid arthritis.

Koumine, an alkaloid, exerts therapeutic effects against rheumatoid arthritis (RA), and thus may have a potential application in novel treatment strategies against this disease. Herein, we investigated the regulatory effect of koumine on Th cell polarization using a "pyramid" structure model to elucidate the mechanism underlying its therapeutic effect on RA. The third layer of the model comprises the cytokine secretion layer, in which the effects of koumine on the balance of Th-related cytokines were investigated in mice with collagen-induced arthritis (CIA). Koumine showed significant therapeutic effects and reversed the imbalance of Th1/Th2 and Th17/Treg cytokines. In the Th cell polarization layer, the effects of koumine on the relative numbers of Th cell subsets in splenocytes of rats with CIA were examined. Koumine attenuated both of the increased Th1/Th2 and Th17/Treg subset ratios accompanied with its therapeutic effects. Finally, the primary cultured splenocytes from BALB/c mice were used to further investigate the effect of koumine on Th cell activation by evaluating cell proliferation induced by concanavalin A (Con A), lipopolysaccharides (LPS) and phytohemagglutinin (PHA). Koumine inhibited the cell proliferation responses and its effects on proliferation induced by Con A and PHA were greater than those by LPS, showing the relatively selective inhibition on the proliferation of Th cells. Our results suggest that koumine might restore the homeostasis of the network system with Th subsets and cytokines by inhibiting the activation of T cells, subsequently regulating the polarization of Th subsets and the downstream imbalance of pro/anti-inflammatory cytokines in RA.

[Effect of low magnitude tension on the inflammatory response of periodontal ligament cells induced by isoproterenol].

PURPOSE: To investigate the effect of tension on the inflammatory response of human periodontal ligament cells (PDLCs) induced by isoproterenol (ISO) and its molecular mechanism. METHODS: Human PDLCs were cultured in vitro and stimulated with a certain concentration of ISO(0.01, 0.1, 1 µmol/L) for 24 h. Cyclic tensile strain with different degrees of elongation (5%, 10% and 15%) were applied. The expression of IL-1ß and IL-6 mRNA in PDLCs was detected by real-time quantitative PCR(RT-qPCR). The protein expression of p-PERK, PERK, p-eIF2α, eIF2α and ATF4 related to ER stress was detected by Western blot. The expression of PERK gene in PDLCs was knocked down by cell transfection technique, and the expression of IL-1ß and IL-6 mRNA in PDLCs with low expression of PERK was detected by RT-qPCR under the stimulation of ISO and low magnitude tension. Statistical analysis was conducted with SPSS 22.0 software package. RESULTS: ISO induction could significantly up-regulate the IL-1ß and IL-6 mRNA expression in PDLCs(P＜0.05). Compared with the control group, the expression of IL-1ß and IL-6 mRNA in PDLCs induced by ISO was inhibited by low magnitude tension, and the difference was statistically significant(P＜0.05). Western blot results showed that low magnitude tension could inhibit the ISO-stimulated phosphorylation of PERK and eIF2α and the expression of ATF4（P＜0.05）. Compared with the negative control group, IL-1ß and IL-6 mRNA expression was decreased in the ISO-stimulated PDLCs silenced by PERK gene. CONCLUSIONS: Tension with 5% degrees of elongation may inhibit ISO-stimulated periodontal inflammatory response through endoplasmic reticulum stress pathway.

Koumine regulates macrophage M1/M2 polarization via TSPO, alleviating sepsis-associated liver injury in mice.

BACKGROUND: Translocator protein (TSPO) is an 18-kDa transmembrane protein found primarily in the mitochondrial outer membrane, and it is implicated in inflammatory responses, such as cytokine release. Koumine (KM) is an indole alkaloid extracted from Gelsemium elegans Benth. It has been reported to be a high-affinity ligand of TSPO and to exert anti-inflammatory and immunomodulatory effects in our recent studies. However, the protective effect of KM on sepsis-associated liver injury (SALI) and its mechanisms are unknown. PURPOSE: To explore the role of TSPO in SALI and then further explore the protective effect and mechanism of KM on SALI. METHODS: The effect of KM on the survival rate of septic mice was confirmed in mouse models of caecal ligation and puncture (CLP)-induced and lipopolysaccharide (LPS)-induced sepsis. The protective effect of KM on CLP-induced SALI was comprehensively evaluated by observing the morphology of the mouse liver and measuring liver injury markers. The serum cytokine content was detected in mice by flow cytometry. Macrophage polarization in the liver was examined using western blotting. TSPO knockout mice were used to explore the role of TSPO in sepsis liver injury and verify the protective effect of KM on sepsis liver injury through TSPO. RESULTS: KM significantly improved the survival rate of both LPS- and CLP-induced sepsis in mice. KM has a significant liver protective effect on CLP-induced sepsis in mice. KM treatment ameliorated liver ischaemia, improved liver pathological injuries, and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and proinflammatory cytokines in serum. Western blotting results showed that KM inhibited M1 polarization of macrophages and promoted M2 polarization. In TSPO knockout mice, we found that TSPO knockout can improve the survival rate of septic mice, ameliorate liver ischaemia, improve liver pathological injuries, and decrease the levels of ALT, AST, and LDH. In addition, TSPO knockout inhibits the M1 polarization of macrophages in the liver of septic mice and promotes M2 polarization and the serum levels of proinflammatory cytokines. Interestingly, in TSPO knockout septic mice, these protective effects of KM were no longer effective. CONCLUSIONS: We report for the first time that TSPO plays a critical role in sepsis-associated liver injury by regulating the polarization of liver macrophages and reducing the inflammatory response. KM, a TSPO ligand, is a potentially desirable candidate for the treatment of SALI that may regulate macrophage M1/M2 polarization through TSPO in the liver.

Analysis of the successful clinical treatment of 140 patients with parathyroid adenoma: A retrospective study.

BACKGROUND: Parathyroid adenoma (PA) sometimes recurs after surgery, how to improve the surgical success rate of PA is the key to the treatment of this disease. AIM: To investigate the clinical features, diagnosis, and surgical treatment of patients with PA. METHODS: Patients who were pathologically confirmed with PA and had undergone surgery for the first time between January 2010 and December 2017 at the Beijing Shijitan Hospital affiliated to Capital Medical University were included in the study. The clinical features, localization diagnosis, and surgical treatment of these patients were analyzed. RESULTS: Of the 140 patients, 32 were male and 108 were female; 132 cases had one adenoma, and 8 had two adenomas. In addition, 114 cases had clinical symptoms, among which 51, 28, 23, 8, and 4 had urinary system, skeletal system, digestive system, neuromuscular system, and neuropsychiatric symptoms, respectively, while 26 cases had no obvious symptoms. The median level of preoperative parathyroid hormone (PTH) was 201.0 pg/mL. The positive detection rate of technetium-99m sestamibi (Tc-99m MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT), ultrasound examination, and the combined use of Tc-99m MIBI SPECT/CT and ultrasound examination was 92.9%, 85.5%, and 96.4%, respectively. Open surgery was performed in all patients, and PTH was monitored during surgery. The success rate of surgery was 98.6%. After surgery, 21 cases developed hypocalcemia, 1 case developed temporary hoarseness, and 19 cases had transient hypoparathyroidism but there was no permanent hypoparathyroidism, postoperative hemorrhage, or hematoma in the surgical area. CONCLUSION: For patients with clinically unexplained skeletal system, urinary system, and neuropsychiatric symptoms, the possibility of PA should be considered. Imaging examinations such as ultrasound and Tc-99m MIBI SPECT/CT could be integrated before surgery to obtain accurate localization diagnosis. Precise preoperative localization, intraoperative PTH monitoring, and delicate surgery to protect the integrity of the PA capsule ensure a minimally invasive and successful surgery.

2-Bromopalmitate decreases spinal inflammation and attenuates oxaliplatin-induced neuropathic pain via reducing Drp1-mediated mitochondrial dysfunction.

Oxaliplatin (OXA) is a third-generation platinum compound with clinical activity in multiple solid tumors. Due to the repetition of chemotherapy cycle, OXA-induced chronic neuropathy presenting as paresthesia and pain. This study explored the neuropathy of chemotherapy pain and investigated the analgesic effect of 2-bromopalmitate (2-BP) on the pain behavior of OXA-induced rats. The chemotherapy pain rat model was established by the five consecutive administration of OXA (intraperitoneal, 4 mg/kg). After the establishment of OXA-induced rats, the pain behavior test, inflammatory signal analysis and mitochondrial function measurement were conducted. OXA-induced rats exhibited mechanical allodynia and spinal inflammatory infiltration. Our fluorescence and western blot analysis revealed spinal astrocytes were activated in OXA rats with up-regulation of astrocytic markers. In addition, NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome mediated inflammatory signal cascade was also activated. Inflammation was triggered by dysfunctional mitochondria which represented by increase in cyclooxygenase-2 (COX-2) level and manganese superoxide dismutase (Mn-SOD) activity. Intrathecally injection of 2-BP significantly attenuated dynamin-related protein 1 (Drp1) mediated mitochondrial fission, recovered mitochondrial function, suppressed NLRP3 inflammasome cascade, and consequently decreased mechanical pain sensitivity. For cell research, 2-BP treatment significantly reversed tumor necrosis factor-α (TNF-α) induced mitochondria membrane potential deficiency and high reactive oxygen species (ROS) level. These findings indicate 2-BP decreases spinal inflammation and relieves OXA-induced neuropathic pain via reducing Drp1-mediated mitochondrial dysfunction.

Environmentally relevant concentrations of microplastics modulated the immune response and swimming activity, and impaired the development of marine medaka Oryzias melastigma larvae.

Microplastics (MPs), due to their impacts on the ecosystem and their integration into the food web either through trophic transfer or ingestion directly from the ambient environment, are an emerging class of environmental contaminants posing a great threat to marine organisms. Most reports on the toxic effects of MPs exclusively focus on bioaccumulation, oxidative stress, pathological damage, and metabolic disturbance in fish. However, the collected information on fish immunity in response to MPs is poorly defined. In particular, little is known regarding mucosal immunity and the role of mucins. In this study, marine medaka (Oryzias melastigma) larvae were exposed to 6.0 µm beads of polystyrene microplastics (PS-MPs) at three environmentally relevant concentrations (102 particles/L, 104 particles/L, and 106 particles/L) for 14 days. The experiment was carried out to explore the developmental and behavioural indices, the transcriptional profiles of mucins, pro-inflammatory, immune, metabolism and antioxidant responses related genes, as well as the accumulation of PS-MPs in larvae. The results revealed that PS-MPs were observed in the gastrointestinal tract, with a concentration- and exposure time-dependent manner. No significant difference in the larval mortality was found between the treatment groups and the control, whereas the body length of larvae demonstrated a significant reduction at 106 particles/L on 14 days post-hatching. The swimming behaviour of the larvae became hyperactive under exposure to 104 and 106 particles/L PS-MPs. In addition, PS-MP exposure significantly up-regulated the mucin gene transcriptional levels of muc7-like and muc13-like, however down-regulated the mucin gene expression levels of heg1, muc2, muc5AC-like and muc13. The immune- and inflammation and metabolism-relevant genes (jak, stat-3, il-6, il-1ß, tnf-а, ccl-11, nf-κb, and sod) were significantly induced by PS-MPs at 104 and 106 particles/L compared to the control. Taken together, this study suggests that PS-MPs induced inflammation response and might obstruct the immune functions and retarded the growth of the marine medaka larvae even at environmentally relevant concentrations.

Resveratrol ameliorates oxaliplatin-induced neuropathic pain via anti-inflammatory effects in rats.

Oxaliplatin (OXA) is a common chemotherapy drug and exhibits clinical activity in several cancer types. Its anticancer clinical effect is frequently accompanied by neurotoxicity. The symptoms include paresthesia and pain, which adversely affect the quality of life of patients. In the present study, five consecutive intraperitoneal injections of 4 mg/kg OXA were used to mimic chemotherapy in rats. OXA administration induced mechanical allodynia, activated spinal astrocytes and triggered the inflammatory response. To explore potential therapeutic options for OXA-induced neuropathic pain, resveratrol (Res) was intrathecally injected into the spinal cord of OXA-treated rats. Paw withdrawal threshold values of OXA-treated rats were increased, indicating an antinociception effect of Res on OXA-induced pain. Additionally, Res treatment reduced the levels of glial fibrillary acidic protein, TNF-α, IL-1ß and NF-κB, which were upregulated in OXA-treated rats (compared with control). Furthermore, Auto Dock data showed that Res binds to cyclooxygenase-2 (COX-2) through six hydrogen bonds. Western blot analysis and reactive oxygen species (ROS) assays indicated that Res treatment decreased COX-2 expression and suppressed ROS production. In summary, intrathecal injection of Res reduced the spinal COX-2-mediated ROS generation and inflammatory reaction, suppressed astrocytic activation, and alleviated OXA-induced neuropathic pain.