Effect of family integrated care on stress in mothers of preterm infants: A multicenter cluster randomized controlled trial.

BACKGROUND: Reducing mother-infant separation in early life is a key breakthrough in the care improvement model in the neonatal intensive care unit (NICU). Previously, we reported effect of family integrated care (FICare) on clinical outcomes of preterm infants. We further clarify effect of FICare on maternal stress. METHODS: Mothers of preterm infants at eleven NICUs were randomized to the FICare group and the control group. The primary outcome was the reduction in Parental Stress Scale: NICU (PSS:NICU) score from enrollment to discharge. RESULTS: Total of 601 mothers (298 in FICare and 303 in control groups) enrolled. There was no significant difference in PSS:NICU score between the 2 groups at enrollment (P = 0.824), and the FICare group had lower scores at discharge (P < 0.001). PSS:NICU scores of both groups were significantly decreased at discharge compared to at enrollment (P < 0.001), and the reduction was greater in the FICare group (P < 0.001). After applying linear regressions to adjust for potential confounders, results remained unchanged (adjusted P < 0.001). PSS:NICU score reductions from enrollment to discharge were positively correlated with maternal age in the control group (ρ = 0.147, P = 0.011). LIMITATIONS: This study was limited to post-hoc analyses and did not include follow-up to evaluate long-term effects. CONCLUSIONS: FICare is helpful for reducing maternal stress in preterm infants in the NICU. Older mothers tend to have limited improvements in stress after traditional nonparent care, which suggests that they may benefit more from the FICare model.

Sanshimao formula inhibits the hypoxia-induced pro-angiogenesis of hepatocellular carcinoma cells partly through regulating MKK6/p38 signaling pathway.

OBJECTIVES: Sanshimao (SSM) is a traditional Chinese medicine formula for advanced hepatocellular carcinoma (HCC). This study was designed to investigate the effect of SSM on HCC-induced angiogenesis and to explore the potential mechanism. METHODS: The endothelial cells were cultured with HCC cells conditioned medium in the 1% oxygen atmosphere to imitate tumor hypoxia microenvironment. EA.hy926 cells migration and tubulogenesis were detected by tube formation and scratch-wound assay. The protein microarray was employed to explore SSM-targeted proteins in Huh7 cells. We also established an animal model to observe the effects of SSM on angiogenesis in vivo. RESULTS: The data indicated that SSM reduced HCC-induced migration and tube formation of EA.hy926 cells at low dose under hypoxic conditions. These effects might be partly owing to suppression of HIF-1α-induced vascular endothelial growth factorα expression in Huh7 cells. Moreover, this inhibition was in an MKK6/P38-dependent way. Besides, Huh7 subcutaneous tumor models in nude mice further demonstrated the inhibition of SSM on tumor weight might be exerted partly by reduction of angiogenesis via blocking MKK6/P38 signaling pathways. CONCLUSION: SSM inhibits HCC-induced pro-angiogenesis under hypoxic conditions via suppression of MKK6/P38 signaling pathways, which is favorable for HCC tumor growth.

Traditional Chinese medicine Dingkun pill to increase fertility in women with a thin endometrium-a prospective randomized study.

Objective: The aim of this study is to optimize the treatment methods of infertility, which is suggested to be mainly caused by thin endometrium, using a special form of traditional Chinese medicine, the Dingkun pill (DKP), to increase the beneficial endometrial effect of conventional hormone/progestogen therapy. Methods: A total of 307 patients visiting our specialized gynecological endocrinology department because of infertility, which we suggested to be caused by thin endometrium [endometrial thickness (EMT) < 7 mm], were randomly assigned to the experimental group and the control group. The experimental group was treated with estradiol + sequential dydrogesterone + DKP (every day); the control group received hormonal treatment without the Chinese medicine. All patients were monitored in terms of follicle diameter, EMT, and endometrial type every 2 days from the 8th to the 10th day of the menstrual cycle until ovulation day during three menstrual cycles. Serum progesterone levels on 7-8 days after ovulation were measured, and the cumulative pregnancy rate during three menstrual cycles between the two groups was compared. Results: EMT on ovulation day in the experimental group was significantly higher than that in the control group (7.88 vs. 7.15 mm; p < 0.001). The proportion of type A and type B endometrium in total was significantly higher in the experimental group than that in the control group (83.2% vs. 77.7%; p < 0.05). Progesterone levels were significantly higher in the experimental group than those in the control group (10.874 vs. 10.074 ng/mL; p < 0.001). The cumulative pregnancy rate, the main outcome of the study, was significantly higher in the experimental group than that in the control group (29.2% vs. 15.7%; p < 0.05). Conclusion: DKP added to conventional estrogen/progestogen therapy can significantly improve EMT and luteal function in patients attending due to infertility. Because this regimen increased the cumulative pregnancy rate in our study, we conclude that DKP can be used to increase the so-called "thin endometrium infertility".

Pharmacologic Ascorbate and DNMT Inhibitors Increase DUOX Expression and Peroxide-Mediated Toxicity in Pancreatic Cancer.

Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) enzymes produce hydrogen peroxide (H2O2) in normal pancreatic tissue but are silenced in pancreatic cancer (PDAC). Treatment of PDAC with pharmacologic ascorbate (P-AscH-, intravenous, high dose vitamin C) increases DUOX expression. We hypothesized that inhibiting DNMT may act synergistically with P-AscH- to further increase DUOX expression and cytotoxicity of PDAC. PDAC cells demonstrated dose-dependent increases in DUOX mRNA and protein expression when treated with DNMT inhibitors. PDAC cells treated with P-AscH- + DNMT inhibitors demonstrated increased DUOX expression, increased intracellular oxidation, and increased cytotoxicity in vitro and in vivo compared to either treatment alone. These findings suggest a potential therapeutic, epigenetic mechanism to treat PDAC.

Inhibition of Cxcr4 Disrupts Mouse Embryonic Palatal Mesenchymal Cell Migration and Induces Cleft Palate Occurrence.

Many processes take place during embryogenesis, and the development of the palate mainly involves proliferation, migration, osteogenesis, and epithelial-mesenchymal transition. Abnormalities in any of these processes can be the cause of cleft palate (CP). There have been few reports on whether C-X-C motif chemokine receptor 4 (CXCR4), which is involved in embryonic development, participates in these processes. In our study, the knockdown of Cxcr4 inhibited the migration of mouse embryonic palatal mesenchymal (MEPM) cells similarly to the use of its inhibitor plerixafor, and the inhibition of cell migration in the Cxcr4 knockdown group was partially reversed by supplementation with C-X-C motif chemokine ligand 12 (CXCL12). In combination with low-dose retinoic acid (RA), plerixafor increased the incidence of cleft palates in mice by decreasing the expression of Cxcr4 and its downstream migration-regulating gene Rac family small GTPase 1 (RAC1) mediating actin cytoskeleton to affect lamellipodia formation and focal complex assembly and ras homolog family member A (RHOA) regulating the actin cytoskeleton to affect stress fiber formation and focal complex maturation into focal adhesions. Our results indicate that the disruption of cell migration and impaired normal palatal development by inhibition of Cxcr4 expression might be mediated through Rac1 with RhoA. The combination of retinoic acid and plerixafor might increase the incidence of cleft palate, which also provided a rationale to guide the use of the drug during conception.

StMLP1, as a Kunitz trypsin inhibitor, enhances potato resistance and specifically expresses in vascular bundles during Ralstonia solanacearum infection.

Miraculin-like proteins (MLPs), members of the Kunitz trypsin inhibitor (KTI) family that are present in various plants, have been discovered to have a role in defending plants against pathogens. In this study, we identified a gene StMLP1 in potato that belongs to the KTI family. We found that the expression of StMLP1 gradually increases during Ralstonia solanacearum (R. solanacearum) infection. We characterized the promoter of StMLP1 as an inducible promoter that can be triggered by R. solanacearum and as a tissue-specific promoter with specificity for vascular bundle expression. Our findings demonstrate that StMLP1 exhibits trypsin inhibitor activity, and that its signal peptide is essential for proper localization and function. Overexpression of StMLP1 in potato can enhance the resistance to R. solanacearum. Inhibiting the expression of StMLP1 during infection accelerated the infection by R. solanacearum to a certain extent. In addition, the RNA-seq results of the overexpression-StMLP1 lines indicated that StMLP1 was involved in potato immunity. All these findings in our study reveal that StMLP1 functions as a positive regulator that is induced and specifically expressed in vascular bundles in response to R. solanacearum infection.

Development and evaluation of a Chinese herbal gel for analgesic and anti-inflammatory effects.

This study aimed to develop a film-forming gel containing three Chinese herbal extracts, an extracted mixture of Corydalis yanhusuo, Cynanchum paniculatum and Armadillidium vulgare (Latreille) (MCCA) and evaluate its analgesic and anti-inflammatory activities. Using the Box Behnken Design, the optimal prescription for the MCCA gel was determined. The analgesic effects were tested through acid writhing and formalin pain models. while the rheumatoid arthritis model assessed the pain and anti-inflammatory effects. For the evaluation of the effect of MCCA gels on pro-inflammatory cytokines, as well, Elisa was used. Results showed that the MCCA Gel with 2% mint oil had the highest transdermal volume of 32.57±0.92µg/cm2. High doses of MCCA gel were effective in suppressing pain, with a pain inhibition rate of 54.37% during the acetic acid peristaltic test that showed pronounced inhibition in the second phase of the formalin-induced analgesia test. In the rheumatoid arthritis model, the MCCA gel reduced inflammation scores in rat feet and decreased the expressions of four inflammatory factors in serum. Generally, The MCCA gel exhibits noticeable pain-relieving and anti-inflammatory properties with high penetration with the skin.

Field-of-view optimized and constrained undistorted single-shot study of intravoxel incoherent motion and diffusion-weighted imaging of the uterus during the menstrual cycle: a prospective study.

PURPOSE: This study aimed to compare the variability of the uterus during the menses phase (MP), follicular phase (FP), and luteal phase (LP) of the menstrual cycle using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). METHODS: This prospective study was conducted at the Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2022 and January 2023. Women of childbearing age (18-45 years) with appropriate progesterone levels were included in this study. Conventional magnetic resonance imaging and IVIM-DWI scans were performed during the MP, FP, and LP. The differences in IVIM-DWI-derived parameters between these phases were then compared, and the overlap was quantitatively described. RESULTS: The apparent diffusion coefficient (ADC) and pure molecular diffusion coefficient (D) values from the endometrium, uterine junctional zone (UJZ), and myometrium indicated statistical differences between the MP and FP and the MP and LP (ADC: endometrium, both P < 0.001; UJZ, P = 0.008 and P < 0.001, respectively; myometrium, P = 0.033 and P = 0.006, respectively; D: endometrium, both P < 0.001; UJZ, P = 0.008 and P = 0.006, respectively; myometrium, P = 0.041 and P = 0.045, respectively). The perfusion-related diffusion coefficient (D*) values from the myometrium indicated statistical differences between the FP and MP and the FP and LP (D*: myometrium, P = 0.049 and P = 0.009, respectively). The overlapping endometrium ratios between the MP and FP or LP were lower than 50% in the ADC and D values (ADC: overlapping of MP and FP: 33.33%, overlapping of MP and LP: 23.33%; D: overlapping of MP and FP: 40.00%, overlapping of MP and LP: 43.33%). CONCLUSION: The ADC and IVIM-derived parameters indicated differences in the uterus in diverse phases of the menstrual cycle, especially in the endometrium in relation to ADC and D values.

Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/ß-catenin pathway under hypoxia.

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/ß-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/ß-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/ß-catenin pathway. CONCLUSION: JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/ß-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/ß-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.

Enhancement for phonon-mediated superconductivity up to 37 K in few-hydrogen metal-bonded layered magnesium hydride under atmospheric pressure.

The discovery of superconductivity in layered MgB2 has renewed interest in the search for high-temperature conventional superconductors, leading to the synthesis of numerous hydrogen-dominated materials with high critical temperatures (Tc) under high pressures. However, achieving a high-Tc superconductor under ambient pressure remains a challenging goal. In this study, we propose a novel approach to realize a high-temperature superconductor under ambient pressure by introducing a hexagonal H monolayer into the hexagonal close-packed magnesium lattice, resulting in a new and stable few-hydrogen metal-bonded layered magnesium hydride (Mg4)2H1. This compound exhibits superior ductility compared to multi-hydrogen, cuprate, and iron-based superconductors due to its metallic bonding. Our unconventional strategy diverges from the conventional design principles used in hydrogen-dominated covalent high-temperature superconductors. Using anisotropic Migdal-Eliashberg equations, we demonstrate that the stable (Mg4)2H1 compound is a typical phonon-mediated superconductor, characterized by strong electron-phonon coupling and an excellent Tc of 37 K under ambient conditions, comparable to that of MgB2. Our findings not only present a new pathway for exploring high-temperature superconductors but also provide valuable insights for future experimental synthesis endeavors.

Soft drinks, tea and coffee consumption in relation to risk of fracture: evidence from china health and nutrition survey.

INTRODUCTION: To investigate the association between soft drinks, tea and coffee consumption, and risk of fracture in the China Health and Nutrition Survey. MATERIALS AND METHODS: A cross-sectional study with multi-stage random cluster sampling was conducted in nine Chinese provinces in 2004, 2006, 2009 and 2011. A total of 36,740 participants were included the data analyses. Self-administered questionnaires and physical examinations provided data on beverages consumption, fracture history, and other potential risk factors. Binary logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for potentially confounding variables. RESULTS: The prevalence of fracture increased over the 7-year period of the surveys, with 1833 (5.3%) participants reporting a fracture history. Soft drink consumption increased over this time period, and tea consumption was relatively stable, whereas coffee consumption tended to increase sharply. Consumers of soft drinks ≥ 3 times/week (versus never) had a higher risk of fracture (OR = 1.86, 95% CI = 1.43-2.32, p < 0.001, p for trend = 0.039). Consumers of tea ≥ 5 cups/day (versus never) also had a higher risk of fracture (OR = 1.21, 95% CI = 1.09-1.45, p = 0.028, p for trend < 0.001). Similarly, consumers of coffee ≥ 2 cups/day (versus never) had a higher risk of fracture (OR = 1.84, 95% CI = 1.01-3.34, p = 0.045, p for trend = 0.002). Subgroup analyses by gender suggested that coffee consumption increased risk of fracture in females (OR = 1.84, 95% CI = 1.32-2.63, p = 0.001). CONCLUSION: Our findings suggest that high consumption of soft drinks, tea and coffee is associated with an increased risk of fracture in the Chinese population. Which has important public health implications given the widespread consumption of these beverages.

Pharmacological ascorbate induces sustained mitochondrial dysfunction.

Pharmacological ascorbate (P-AscH-; high dose given intravenously) generates H2O2 that is selectively cytotoxic to cancer compared to normal cells. The RAS-RAF-ERK1/2 is a major signaling pathway in cancers carrying RAS mutations and is known to be activated by H2O2. Activated ERK1/2 also phosphorylates the GTPase dynamin-related protein (Drp1), which then stimulates mitochondrial fission. Although early generation of H2O2 leads to cytotoxicity of cancer cells, we hypothesized that sustained increases in H2O2 activate ERK-Drp1 signaling, leading to an adaptive response; inhibition of this pathway would enhance the toxicity of P-AscH-. Increases in phosphorylated ERK and Drp1 induced by P-AscH- were reversed with genetic and pharmacological inhibitors of ERK and Drp1, as well as in cells lacking functional mitochondria. P-AscH- increased Drp1 colocalization to mitochondria, decreased mitochondrial volume, increased disconnected components, and decreased mitochondrial length, suggesting an increase in mitochondrial fission 48 h after treatment with P-AscH-. P-AscH- decreased clonogenic survival; this was enhanced by genetic and pharmacological inhibition of both ERK and Drp1. In murine tumor xenografts, the combination of P-AscH- and pharmacological inhibition of Drp1 increased overall survival. These results suggest that P-AscH- induces sustained changes in mitochondria, through activation of the ERK/Drp1 signaling pathway, an adaptive response. Inhibition of this pathway enhanced the toxicity P-AscH- to cancer cells.

The mediation of the AHR/IL-22/STAT3/IL-6 axis by soft-shelled turtle (Pelodiscus sinensis) peptide and Chinese pond turtle (Chinemys reevesii) peptide contributed to their amelioration effects on intestinal mucosal immunity in immunosuppressed mice.

This study investigated the immunomodulatory effects of soft-shelled turtle (Pelodiscus sinensis) peptide (TP) and Chinese pond turtle (Chinemys reevesii) peptide (TMP) on the intestinal mucosal immune system (IMIS). The results demonstrated that TP and TMP improved holistic immunity by restoring the vital immune organ atrophy and proliferation capacity of spleen immune cells. Moreover, TP and TMP significantly increased the serum content of IgA and cytokines that are responsible for immune cell activation and antigen clearance. TP and TMP promoted intestinal B cell activation, class switching recombination, and antibody secreting processes in a T cell-independent manner to increase the SIgA content. Furthermore, TP and TMP enhanced the intestinal barrier by increasing the protein expression of tight junctions (TJs) and adhesion junctions (AJs) and ameliorating the intestinal morphology. Mechanistically, TP and TMP activated the AHR/IL-22/STAT3/IL-6 axis to enhance the IgA response and improve the intestinal barrier, indicating their potential in intestinal health modulation.

A Phytophthora infestans RXLR effector AVR8 suppresses plant immunity by targeting a desumoylating isopeptidase DeSI2.

The potato's most devastating disease is late blight, which is caused by Phytophthora infestans. Whereas various resistance (R) genes are known, most are typically defeated by this fast-evolving oomycete pathogen. However, the broad-spectrum and durable R8 is a vital gene resource for potato resistance breeding. To support an educated deployment of R8, we embarked on a study on the corresponding avirulence gene Avr8. We overexpressed Avr8 by transient and stable transformation, and found that Avr8 promotes colonization of P. infestans in Nicotiana benthamiana and potato, respectively. A yeast-two-hybrid (Y2H) screen showed that AVR8 interacts with a desumoylating isopeptidase (StDeSI2) of potato. We overexpressed DeSI2 and found that DeSI2 positively regulates resistance to P. infestans, while silencing StDeSI2 downregulated the expression of a set of defense-related genes. By using a specific proteasome inhibitor, we found that AVR8 destabilized StDeSI2 through the 26S proteasome and attenuated early PTI responses. Altogether, these results indicate that AVR8 manipulates desumoylation, which is a new strategy that adds to the plethora of mechanisms that Phytophthora exploits to modulate host immunity, and StDeSI2 provides a new target for durable resistance breeding against P. infestans in potato.

Excellent Repigmentation of Generalized Vitiligo with Oral Baricitinib Combined with NB-UVB Phototherapy.

Vitiligo is an acquired autoimmune skin disorder, clinically characterized by distinct white macules and patches resulting from progressive melanocyte destruction. JAK-STAT pathway plays an important role in the loss of epidermal melanocytes. Baricitinib can block the JAK-STAT pathway and the downstream chemokines as a new JAK1/2 inhibitor. In this report, we describe the successful treatment of 2 patients with oral baricitinib combined with NB-UVB phototherapy, which provides a good alternative and supplementary to treat refractory vitiligo.

Effects of mowing on Pb accumulation and transport in Cynodon dactylon (L.) Pers.

Bermudagrass is a perennial herb with the potential to remediate Pb pollution in soils, and it has mechanical resistance to shearing. However, the effects of mowing on Pb absorption and accumulation in bermudagrass are still unclear. In this study, we investigated the effects of different quantities (0, 1, 2, 4 applications) of mowing treatments under 200 mg L-1 Pb application on Pb accumulation and transport in bermudagrass and explored the related mechanisms. Compared to the Pb treatment, all of the mowing treatments greatly decreased root Pb concentration/accumulation, significantly enhanced Pb concentrations/accumulations in stubble stems and stubble leaves, and ultimately promoted Pb enrichment and transport. Of the treatments in this study, two applications of mowing best promoted Pb enrichment, and four applications of mowing best promoted Pb transport efficiency. Furthermore, mowing mediated the microdistribution and physiological patterns of Pb in bermudagrass and affected the Pb transport by changing the subcellar distribution patterns and chemical forms of Pb in various tissues. Additionally, mowing promoted the transport of all mineral elements and showed a synergistic relationship with Pb absorption and transport. The change in mineral element metabolism patterns may be an important reason why mowing promoted Pb accumulation in bermudagrass. Our study provides the first comprehensive evidence regarding mowing facilitating the absorption, accumulation and transport of Pb in bermudagrass. Moderate mowing may be an effective strategy to assist in soil Pb remediation using bermudagrass.

Preparation, characterization and safety evaluation of Ligusticum chuanxiong essential oils liposomes for treatment of cerebral ischemia-reperfusion injury.

The essential oils of Ligusticum chuanxiong Hort. (CXEO) are considered to be important parts of the pharmacological action of Ligusticum chuanxiong Hort. CXEO have a wide range of applications in various fields. Despite the interesting properties of CXEO, the volatility and low solubility have limited the application. Liposomes are vesicles composed of concentric bilayer lipids arranged around the water environment. Therefore, this study aimed to prepare stable CXEO liposomes (CXEO-LP) to improve the properties. Then, CXEO-LP were prepared by thin film dispersion method and optimized. The results showed that CXEO-LP were well dispersed. Subsequently, in vitro release and antioxidant properties of CXEO-LP were researched. CXEO-LP had slow release effect and oxidation resistance, indicating CXEO-LP may be a potential drug for treating cerebral ischemia-reperfusion injury (CIRI). The nasal mucosa toxicity test and acute toxicity test showed that CXEO-LP had no obvious toxicity to nasal cavity, heart, liver, spleen, lung and kidney tissues. Pharmacodynamic studies found that CXEO-LP significantly improved neurological deficits and brain pathology in a mouse model of CIRI compared to CXEO after intranasal administration. In general, this study showed that CXEO-LP were easy to prepare and continuously released, and had an important development prospect in the treatment of CIRI.

Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1α/NLRP3 signaling following thalamic hemorrhagic stroke.

BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

The changes and potential effects of zinc homeostasis in periodontitis microenvironment.

Zinc is a very important and ubiquitous element, which is present in oral environment, daily diet, oral health products, dental restorative materials, and so on. However, there is a lack of attention to the role of both extracellular or intracellular zinc in the progression of periodontitis and periodontal regeneration. This review summarizes the characteristics of immunological microenvironment and host cells function in several key stages of periodontitis progression, and explores the regulatory effect of zinc during this process. We find multiple evidence indicate that zinc may be involved and play a key role in the stages of immune defense, inflammatory response and bone remodeling. Zinc supplementation in an appropriate dose range or regulation of zinc transport proteins can promote periodontal regeneration by either enhancing immune defense or up-regulating local cells proliferation and differentiation functions. Therefore, zinc homeostasis is essential in periodontal remodeling and regeneration. More attention is suggested to be focused on zinc homeostasis regulation and consider it as a potential strategy in the studies on periodontitis treatment, periodontal-guided tissue regeneration, implant material transformation, and so on.

Discovery of a triphenylamine-benzofuran derivative as fluorescent probe for hydrogen polysulfide in tea samples.

In this work, a novel triphenylamine-benzofuran derived fluorescent probe, TBF-SS, was developed for detecting hydrogen polysulfide in tea samples and intracellular imaging. TBF-SS showed the practical advantages including high sensitivity (LOD = 0.01 µM), high selectivity, rapid response (within 15 min), and steadiness in various environmental conditions. The detecting system was steady within pH range of 6.0-11.0 and temperature range of 20-55 °C. The probe TBF-SS could guarantee the stable detection of H2Sn for 7 d in storage of either solid or solution. In particular, in the application of various tea samples with different brewing times and testing temperatures, the recovery percentages varied in the range of 95.22 % to 105.0 %. Therefore accurate monitoring of H2Sn could be achieved by using the probe TBF-SS. In addition, TBF-SS could monitor the exogenous level, the ß-lapachone-induced generation and the tea-sample-treated introduction of H2Sn in living MCF-7 cells. This work might inspire the improvement of the serviceability of fluorescent implements.