Fetal sexual dimorphism of maternal thyroid function parameters during pregnancy, a single center retrospective real-world study.

Introduction: Thyroid function during pregnancy fluctuates with gestational weeks, seasons and other factors. However, it is currently unknown whether there is a fetal sex-specific thyroid function in pregnant women. The purpose of this study was to investigate the fetal sex differences of maternal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in pregnant women. Methods: This single-center retrospective real-world study was performed by reviewing the medical records of pregnant women who received regular antenatal health care and delivered liveborn infants in Shanghai First Maternity and Infant Hospital (Pudong branch), from Aug. 18, 2013 to Jul. 18, 2020. Quantile regression was used to evaluate the relationship between various variables and TSH and FT4 concentrations. The quantile regression also evaluated the sex impact of different gestational weeks on the median of TSH and FT4. Results: A total of 69,243 pregnant women with a mean age of 30.36 years were included. 36197 (52.28%) deliveries were boys. In the three different trimesters, the median levels (interquartile range) of TSH were 1.18 (0.66, 1.82) mIU/L and 1.39 (0.85, 2.05) mIU/L, 1.70 (1.19, 2.40) mIU/L; and the median levels (interquartile range) of FT4 were 16.63 (15.16, 18.31) pmol/L, 14.09 (12.30, 16.20) pmol/L and 13.40 (11.52, 14.71) pmol/L, respectively. The maternal TSH upper limit of reference ranges was decreased more in mothers with female fetuses during gestational weeks 7 to 12, while their FT4 upper limit of the reference ranges was increased more than those with male fetuses. After model adjustment, the median TSH level was 0.11 mIU/L lower (P <0.001), and FT4 level was 0.14 pmol/L higher (P <0.001) for mothers with female fetuses than those with male fetuses during gestational weeks 9 to 12. Discussion: We identified sexual dimorphism in maternal thyroid function parameters, especially during 9-12 weeks of pregnancy. Based on previous research, we speculated that it may be related to the higher HCG levels of mothers who were pregnant with girls during this period. However, longitudinal studies are needed to determine if fetal sex differences impact the maternal thyroid function across pregnancy.

Human Placenta Decellularized Extracellular Matrix Hydrogel Promotes the Generation of Human Spinal Cord Organoids with Dorsoventral Organization from Human Induced Pluripotent Stem Cells.

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization.

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

Determinants affecting the blood mercury levels of preschool children in Shanghai, China: A cross-sectional study.

Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 µg/L, with a median concentration of 1.34 µg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities.

Effects of food-borne cholesterol supplementation on lead-induced neurodevelopmental impairments of rats based on BDNF signaling pathway and cholesterol metabolism.

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-ß levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.

Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer.

Pancreatic cancer is a lethal malignancy for which there is currently no effective treatment strategy. We previously reported that p21-activated kinase 1 (PAK1) is aberrantly expressed in pancreatic cancer patients and that targeted inhibition of PAK1 significantly suppressed pancreatic cancer progression in vitro and in vivo. In this study, we identified the drug azeliragon as a novel inhibitor of PAK1. Cell experiments revealed that azeliragon abolished PAK1 activation and promoted apoptosis in pancreatic cancer cells. Azeliragon was also found to significantly inhibit tumor growth in a pancreatic cancer xenograft model; when combined with afuresertib, an oral pan-AKT kinase inhibitor, azeliragon exhibited a strong synergistic effect against pancreatic cancer cells. Interestingly, afuresertib enhanced the antitumor efficacy of azeliragon in a xenograft mouse model. Collectively, our findings revealed previously unreported aspects of the drug azeliragon, and identified a novel combination strategy for the treatment of pancreatic cancer patients.

Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury.

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 µm, and also had the ability to activate the PDGFRß of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.

Prenatal second-hand smoke exposure and the risk of suspected developmental coordination disorder in preschoolers: A nationwide retrospective cohort study in China.

Prenatal exposure to second-hand smoke (SHS) is associated with increased neurodevelopmental problems in children, however, its impact on the risk of developmental coordination disorder (DCD) in preschoolers have not been studied thoroughly. Herein, we probed this association based on a nationwide retrospective cohort study of 149,005 preschoolers in China. We divided the objects into the prenatal SHS-exposed group or the no prenatal smoke exposed group (NS-exposed group). Preschoolers were assessed for motor proficiency by the Chinese version of Little Developmental Coordination Disorder Questionnaire (LDCDQ). Multivariable logistic regression was used to evaluate the associations. The prevalence of prenatal SHS exposure was 23.89%. Generally, the prevalence of suspected DCD was significantly higher in prenatal SHS-exposed group (16.38% VS. 14.19%, P < 0.001). With the increase of age, the mean total scores of LDCDQ of both boys and girls increased gradually; and the prevalence of suspected DCD in girls was higher than that in boys in the same age group. After adjusting for covariates, prenatal SHS exposure had the negative association with the total score of LDCDQ and increased the risk of suspected DCD. Our results suggest a need for interventions designed to reduce maternal SHS exposure during pregnancy, early screen for DCD and increase targeted movement and coordination skill training for vulnerable children.

Systemic pharmacological verification of Guizhi Fuling decoction in treating endometriosis-associated pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi Fuling decoction (GZFL decoction) is a famous formula in the Synopsis of the Golden Chamber, which has a long history in treating endometriosis. However, its exact mechanism remains unclear. AIM OF STUDY: This study aims to explore the mechanism of GZFL decoction in treating endometriosis, especially in alleviating endometriosis-associated pain. MATERIALS AND METHODS: A combination of system pharmacology and pharmacodynamics was used to explore the specific mechanism of GZFL decoction in the treatment of endometriosis-associated pain. First, the TCMSP database was used to search the components of the GZFL decoction; the parameter index was set as oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18, while the active ingredients of the drug were screened out. The disease targets of endometriosis were obtained from the TTD, OMIM, Genecards, and DisGeNET databases; the keyword was "endometriosis pain". Network construction and analysis were performed using Cytoscape 3.7.2 software; the David database was used to enrich and analyze the pathways for alleviating endometriosis pain after GZFL decoction treatment. In addition, the network results were verified using experimental animal and cell research. RESULTS: The results showed the following targets: 76 for the effective chemical components in the prescription, 1329 for disease pain, and 278 for the intersection of drugs and endometriosis pain. The enrichment results for these targets showed that the TNF-PI3K/Akt pathway exhibited research significance. In endometriosis rat models, the GZFL decoction reduced the volume of lesions and relieved pain symptoms. It also reduced the serum levels of IL-6, IL-1ß, and TNF-α as well as their expression in the lesion tissues. The GZFL decoction also suppressed the activation of PI3K/Akt downstream signaling proteins. CONCLUSIONS: GZFL decoction could reduce the volume of lesions, suppress inflammation, and decrease the sensitivity to pain in endometriosis rat models through inhibiting PI3K/Akt pathway. This study provides a possible target for traditional Chinese medicine in treating endometriosis-associated pain.

Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells.

Shikonin is the main component of root extracts from the Chinese herbal medicine Lithospermum erythrorhizon, which is commonly used for the treatment of various diseases including cancer. Previous research showed that shikonin suppressed pancreatic cancer growth; nevertheless, its molecular targets and mechanisms have not been elucidated. This study aimed to investigate the interaction and regulatory mechanisms of shikonin on its potential target p21-activated kinase 1 (PAK1). Through a labchip-based screening method, shikonin was identified as a potential bioactive PAK1 inhibitor. Molecular docking technology was used to detect the interaction sites of shikonin and PAK1 kinase. Western blot was performed to validate the mechanism. MTT and flow cytometry were practiced to investigate the effect of shikonin against pancreatic cancer cells. The results show that shikonin significantly inhibited the activity of PAK1 kinase with IC50 value of 7.252 ± 0.054 µM. Molecular docking studies showed that shikonin binds to the ATP-binding pocket of the PAK1 kinase domain. Moreover, shikonin inhibited PAK1 activation and its downstream signaling pathway proteins, while reducing proliferation and inducing apoptosis of pancreatic cancer cells. Further studies showed that the treatment of shikonin sensitized pancreatic cancer cells to chemotherapeutic drugs. These results suggest that shikonin, a potential natural inhibitor targeting PAK1 kinase, has promising potent applications in the treatment of pancreatic cancer and chemotherapy sensitization.

Subclinical hypothyroidism in pregnancy rats impaired offspring's spatial learning and memory and the cerebellar development.

Subclinical hypothyroidism (SCH) is a very common preclinical condition during pregnancy. The adverse effect of maternal clinical hypothyroidism (CH) on the nervous system development of offspring is beyond doubt, but it is still controversial in SCH. The aim of this study was to investigate whether spatial learning and memory ability of offspring is inhibited in SCH rat model and its possible mechanism. 45 Wistar female rats were randomly divided into SCH, CH and control (CON) groups, which were induced by semi-thyroid electrocauterization, total thyroidectomy and sham operation, respectively. Rat pups were sacrificed at embryonic day 14 (E14), E18, postnatal day 1 (P1), P3, and P10, and pups' cerebellar tissues were collected. The proliferation, differentiation and migration of cerebellar cells were observed, and RNA level of the thyroid hormone receptor α (TRα) and TRß in the cerebellum was detected by real-time PCR, respectively. Morris Water Maze (MWM) test was performed to detect the spatial learning and memory ability of pups at P40. Our data indicated that maternal SCH will significantly extend the offspring's escape latency time, and pups perform worse in the spatial probe test compared with the CON group. Except for E14, the proliferation of pups' cerebellar granule cells (GCs), and the migration of pups' Purkinje cells (PCs) in the SCH group was significantly inhibited compared with that in the CON group at other time points (P < 0.05 or P < 0.01), and the differentiation of cerebellar astrocytes (As) in SCH group was higher than that in CON group at P3 and P10. Except for E14, the expression of TRα mRNA in SCH group was significantly lower than that in CON group (P < 0.05 or P < 0.01). And the difference of the differentiation of As and the spatial learning and memory between SCH and CH groups was not statistically significant. Our findings suggested that SCH during pregnancy nuisances the offspring's spatial learning and memory. It may be related to the decrease of the expression of TRα in cerebellum, which may further inhibit the proliferation of GCs and the migration of PCs, and increase the differentiation of As.

Effect of Shixiao San on inflammatory factors and pain in rats with endometriosis.

ETHNOPHARMACOLOGICAL RELEVANCE: In the practice of traditional Chinese medicine, endometriosis is believed to be caused by blood stasis and is characterised by dysmenorrhea, which is difficult to control. Shixiao San (SXS) has a long history of use in the treatment of gynaecological diseases. The prescriptions composed of SXS include Typhae Pollen and Faeces Trogopterori, both of which have anti-inflammatory activity. In addition, Typhae Pollen can be used to treat many kinds of blood stasis diseases. AIM OF THE STUDY: The purpose of the present study was to investigate the effect of SXS on pain relief in rats with endometriosis and to preliminarily explore its mechanism of action in alleviating pain. MATERIAL AND METHODS: Ten rats received sham operation as the Sham group, and 30 endometriosis model rats were randomly divided into three groups: the Model, Shixiao San-Low (SXS-L), and Shixiao San-High (SXS-H) groups. The rats were administered the appropriate treatment via intragastric gavage for 4 weeks. The thermal radiation pain and mechanical pain thresholds of the rats were measured every 7 days after treatment. Finally, the distribution density of nerve fibres in endometrial tissue, the inflammatory infiltration of the dorsal root ganglion (DRG), the expression of TRPV1 in the DRG, and the expression of IL-1ß, TNF-α, and IL-6 in ectopic tissue were measured. RESULTS: After SXS treatment, the growth of ectopic tissue in rats with endometriosis was significantly suppressed, their thermal radiation pain and mechanical pain thresholds increased, the density of nerve fibres and the expression of inflammatory factors in ectopic tissues reduced, and inflammatory cells infiltration in the DRG of the animals alleviated. Meanwhile, the expression of TRPV1 in the DRG was downregulated in rats with endometriosis. CONCLUSIONS: SXS could possibly inhibit the development of endometriosis and relieve pain in patients with endometriosis by reducing inflammatory responses in ectopic tissue and the DRG.

Makatoxin-3, a thermostable Nav1.7 agonist from Buthus martensii Karsch (BmK) scorpion elicits non-narcotic analgesia in inflammatory pain models.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic pain management represents a serious healthcare problem worldwide. The use of opioid analgesics for pain has always been hampered by their side effects; in particular, the addictive liability associated with chronic use. Finding a morphine replacement has been a long-standing goal in the field of analgesia. In traditional Chinese medicine, processed Buthus martensii Karsch (BmK) scorpion has been used as a painkiller to treat chronic inflammatory arthritis and spondylitis, so called "Scorpio-analgesia". However, the molecular basis and the underline mechanism for the Scorpio-analgesia are still unclear. AIM OF THE STUDY: The study aims to investigate the molecular basis of "Scorpio analgesia" and identify novel analgesics from BmK scorpion. MATERIALS AND METHODS: In this study, the analgesic abilities were determined using formalin-, acetic acid- and complete Freund's adjuvant-induced pain models. The effect of BmK venom and processed BmK venom on Nav1.7 were detected by whole-cell voltage-clamp recordings on HEK293-hNav1.7 stable cell line. Action potentials in Dorsal root ganglion (DRG) neurons induced by Makatoxin-3-R58A were recorded in current-clamp mode. The content of Makatoxin-3 was detected using competitive enzyme-linked immunosorbent assay based on the Makatoxin-3 antibody. High performance liquid chromatography, western blot and circular dichroism spectroscopy were used to analysis the stability of Makatoxin-3. RESULTS: Here we demonstrate that Makatoxin-3, an α-like toxin in BmK scorpion venom targeting Nav1.7 is the critical component in Scorpio-analgesia. The analgesic effect of Makatoxin-3 could not be reversed by naloxone and is more potent than Nav1.7-selective inhibitors and non-steroidal anti-inflammatory drugs in inflammatory models. Moreover, a R58A mutant of Makatoxin-3 is capable of eliciting analgesia effect without inducing pain response. CONCLUSIONS: This study advances ion channel biology and proposes Nav1.7 agonists, rather than the presumed Nav1.7-only blockers, for non-narcotic relief of chronic pain.

Studies on Children With Developmental Coordination Disorder in the Past 20 Years: A Bibliometric Analysis via CiteSpace.

Children with developmental coordination disorder (DCD) have been commonly observed and drawn an increasing amount of attention over the past decades. The aim of the present study is to evaluate the origin, current hotspots, and research trends on children with DCD using a bibliometric tool. After searching with "children" and "developmental coordination disorder" as the "topic" and "title" words, respectively, 635 original articles with 12,559 references were obtained from the electronic databases, Web of Science Core Collection (WoSCC). CiteSpace V.5.7.R2 was used to perform the analysis. The number of publications in this field was increasing over the past two decades. John Cairney from the Department of Family Medicine, McMaster University, Canada, was found to be the most productive researcher. Meanwhile, McMaster University and Canada were the most productive research institution and country, respectively. Reference and journal co-citation analyses revealed the top landmark articles and clusters in this field. Clumsiness was the most strength burst keyword. Moreover, task, meta-analysis, difficulty, adult, and impact will be the active research hotspots in future. These findings provide the trends and frontiers in the field of children with DCD, and valuable information for clinicians and scientists to identify new perspectives with potential collaborators and cooperative countries.

ZhiJingSan Inhibits Osteoclastogenesis via Regulating RANKL/NF-κB Signaling Pathway and Ameliorates Bone Erosion in Collagen-Induced Mouse Arthritis.

Bone erosion is the most evident pathological condition of rheumatoid arthritis (RA), which is the main cause of joint deformities and disability in RA patients. At present, the conventional RA drugs have not achieved satisfactory effect in improving bone erosion. ZhiJingSan (ZJS), which is a traditional Chinese prescription composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch, scolopendridae) and scorpion (dried body of Buthus martensii Karsch, Buthus), exhibits anti-rheumatism, analgesic and joint deformities improvement effects. This study aimed to assess the therapeutic effect of ZJS on RA bone erosion and to elucidate the underlying mechanism. The effect of ZJS on RA bone erosion was investigated in a murine model of bovine collagen-induced arthritis (CIA), and the underlying mechanism was investigated in vitro in an osteoclast differentiation cell model. Administration of ZJS delayed the onset of arthritis, alleviated joint inflammation, and attenuated bone erosion in the CIA mice. Meanwhile, ZJS decreased the serum levels of TNF-α, IL-6, and anti-bovine collagen II-specific antibodies. Furthermore, ZJS treatment reduced the number of osteoclasts and the expression of cathepsin K in the ankle joints of CIA mice. ZJS also inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and the expression of MMP9 and cathepsin K in vitro. Mechanistically, ZJS blocked RANKL-induced p65 phosphorylation, nucleation, and inhibited the expression of downstream NFATc1 and c-Fos in bone marrow-derived macrophages (BMMs). Taken together, ZJS exerts a therapeutic effect on bone erosion in CIA mice by inhibiting RANKL/NF-κB-mediated osteoclast differentiation, which suggested that ZJS is a promising prescription for treating RA bone erosion.

DHA ameliorates MeHg­induced PC12 cell apoptosis by inhibiting the ROS/JNK signaling pathway.

Recent studies have reported that methylmercury (MeHg) induces neuronal apoptosis, which is accompanied by abnormal neurological development. Despite the important role of docosahexaenoic acid (DHA) in maintaining the structure and function of the brain, as well as improving neuronal apoptosis induced by MeHg, the exact mechanism remains unknown. The present study hypothesized that the reactive oxygen species (ROS)­mediated JNK signaling pathway may be associated with the protective effect of DHA against MeHg­induced PC12 cell apoptosis. Cell Counting Kit­8, TUNEL staining, flow cytometry, ROS detection, PCR and western blot analysis were performed. The results demonstrated that MeHg inhibited the activity of PC12 cells, causing oxidative damage and promoting apoptosis; however, DHA significantly attenuated this effect. Mechanistic studies revealed that MeHg increased intracellular ROS levels and JNK protein phosphorylation, and decreased the expression levels of the anti­apoptotic protein Bcl­2, whereas DHA reduced ROS levels and JNK phosphorylation, and increased Bcl­2 expression. In addition, the ROS inhibitor N­acetyl­l­cysteine (NAC) was used to verify the experimental results. After pretreatment with NAC, expression levels of Bcl­2, Bax, phosphorylated­JNK and JNK were assessed. Bcl­2 protein expression was increased and the Bcl­2/Bax ratio was increased. Moreover, the high expression levels of phosphorylated­JNK induced by MeHg were significantly decreased. Based on the aforementioned results, the present study indicated that the effects of DHA against MeHg­induced PC12 cell apoptosis may be mediated via the ROS/JNK signaling pathway.

Soufeng sanjie formula alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice. METHODS: For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4+ T cells under Th17 polarization conditions. RESULTS: SF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions. CONCLUSIONS: Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.

Ten Years of the Cohort Biobank: Bibliometric Outcomes.

Background: Cohort studies with biobanks that use strict quality standards are essential requirements, not only for the development of new diagnostic and prognostic markers, but also for improving the understanding of pathophysiology of disease development, which have drawn an increasing amount of attention over the past decades. However, a bibliometric analysis of the global research on cohort biobanks is rare. The objective of this study was to evaluate the origin, current trend, and research hotspots of cohort biobanks. Materials and Methods: We searched the Web of Science Core Collection (WoSCC) with "biobank" and "cohort" as the topic words to retrieve English language articles published from 2009 to 2018. The CiteSpace 5.5.R2 was used to perform the cooperation network analysis, key words co-occurrence and burst detection analysis, and reference co-citation analysis. Results: The number of publications on cohort biobanks has increased over the past decade. Tai Hing Lam from the Department of Community Medicine, University of Hong Kong, was found to be the most productive researcher in this field. The percentage of publications in England (38.30%) was the highest all over the world. Risk, biobank, meta-analysis, cohort, disease, and so on were the most frequent keywords. Metabolic syndrome was the strongest burst keyword in this field, followed by Hong Kong, Guangzhou biobank cohort and personalized medicine. Moreover, of all the references for 932 articles included in the study, the article titled "UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age" published in PLoS Med by Sudlow et al., was the most frequently co-cited reference in this field. The largest cluster was labeled as Guangzhou biobank cohort study. Conclusions: This study provides an insight into cohort biobanks and the valuable information for biobankers to identify new perspectives on potential collaborators and cooperative countries/territories.

Association between prenatal exposure to persistent organic pollutants and neurodevelopment in early life: A mother-child cohort (Shanghai, China).

As common environmental pollutants, persistent organic pollutants (POPs) that are widely applied in industry and agriculture have adverse effects on neurodevelopment. However, evidence on the neurotoxicity of POPs in neural development of offspring is limited. This study explored the relationship between prenatal exposure to POPs and neurodevelopment of 18-month-old toddlers in a mother-child cohort in Shanghai, China. In this study, we determined exposure levels of 37 POPs in cord blood serum collected at the time of delivery. The detection rate of pollutants HCB, ß-HCH, and p,p'-DDE was higher than 60%, so these will be discussed in the following analysis. From birth to approximately 18 months, we followed up infants to longitudinally explore whether POPs influenced their language, motor, and cognitive development according to a Bayley-Ⅲ assessment . Based on multivariable regression analyses, the ß-HCH concentration in cord serum was negatively related to motor development scores in children at 18 months by adjusting for the covariates, but there was no change in language and cognition. Further piecewise linear regression analysis showed that a cord serum ß-HCH concentration greater than 0.2 µg/L had a significantly negative correlation with the motor development scores. p,p'-DDE was positively associated with language development at 18 months before and after adjusting for covariates. But prenatal HCB levels were not associated with any of the Bayley-Ⅲ subscales at 18 months. We concluded that prenatal exposure to ß-HCH might have adverse effects on infants' motor development. The minimum harmful concentration of ß-HCH was estimated at 0.2 µg/L in cord serum. The unexpected positive association between p,p'-DDT and language development could be due to live birth bias.