Zinc alleviates thermal stress-induced damage to the integrity and barrier function of cultured chicken embryonic primary jejunal epithelial cells via the MAPK and PI3K/AKT/mTOR signaling pathways.

Zinc (Zn) could alleviate the adverse effect of high temperature (HT) on intestinal integrity and barrier function of broilers, but the underlying mechanisms remain unclear. We aimed to investigate the possible protective mechanisms of Zn on primary cultured broiler jejunal epithelial cells exposed to thermal stress (TS). In Exp.1, jejunal epithelial cells were exposed to 40℃ (normal temperature, NT) and 44℃ (HT) for 1, 2, 4, 6, or 8 h. Cells incubated for 8 h had the lowest transepithelial resistance (TEER) and the highest phenol red permeability under HT. In Exp.2, the cells were preincubated with different Zn sources (Zn sulfate as iZn and Zn proteinate with the moderate chelation strength as oZn) and Zn supplemental levels (50 and 100 µmol/L) under NT for 24 h, and then continuously incubated under HT for another 8 h. TS increased phenol red permeability, lactate dehydrogenase (LDH) activity and p-PKC/PKC level, and decreased TEER, cell proliferation, mRNA levels of claudin-1, occludin, zona occludens-1 (ZO-1), PI3K, AKT and mTOR, protein levels of claudin-1, ZO-1 and junctional adhesion molecule-A (JAM-A), and the levels of p-ERK/ERK, p-PI3K/PI3K and p-AKT/AKT. Under HT, oZn was more effective than iZn in increasing TEER, occludin, ZO-1, PI3K, and AKT mRNA levels, ZO-1 protein level, and p-AKT/AKT level; supplementation with 50 µmol Zn/L was more effective than 100 µmol Zn/L in increasing cell proliferation, JAM-A, PI3K, AKT, and PKC mRNA levels, JAM-A protein level, and the levels of p-ERK/ERK and p-PI3K/PI3K; furthermore, supplementation with 50 µmol Zn/L as oZn had the lowest LDH activity, and the highest ERK, JNK-1, and mTOR mRNA levels. Therefore, supplemental Zn, especially 50 µmol Zn/L as oZn, could alleviate the TS-induced integrity and barrier function damage of broiler jejunal epithelial cells possibly by promoting cell proliferation and tight junction protein expression via the MAPK and PI3K/AKT/mTOR signaling pathways.

HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

Rebuilding the behavioral inhibition circuit to prevent opioid relapse.

Failure in behavioral suppression is a key feature in substance use disorders, potentially leading to compulsive drug seeking and relapse. In this issue of Neuron, Paniccia et al.1 elucidated a heroin-damaged paraventricular nucleus of the thalamus (PVT)-accumbal circuit and how recovery of PVT function could prevent heroin relapse.

Exploring the Impact of High-Quality Nursing on Nursing Efficiency and Stress Levels through Visual Electrophysiological Detection.

Objective: To assess the influence of high-quality nursing during visual electrophysiology examinations on both nursing outcomes and stress levels. Methods: A total of 80 patients who underwent visual electrophysiology examinations in the hospital from January 2021 to January 2022 were included as study subjects and randomized into two groups using random allocation. This random assignment ensures that each patient has an equal chance of being assigned to either group, minimizing the effects of confounding variables and evenly distributing potential bias. The control group received conventional nursing care, while the study group received quality nursing care, with 40 patients in each group. Patients in both groups were compared regarding nursing impact, occurrence of adverse reactions, pain level, and stress status. Results: In the study group, 39 patients exhibited high levels of cooperation, while 1 demonstrated a low degree of cooperation. Conversely, in the control group, 36 subjects were highly cooperative, but 6 displayed a low degree of cooperation. The cooperation rate was significantly higher in the study group compared to the control group (97.5% vs. 85.0%, χ² = 3.914, P = .048). SAS scores and SDS scores after treatment were observed to be lower in the study group compared to those in the control group (P < .05). The increase in scores within the study group was notably less than that observed in the control group (P < .05). The results indicate that 38 patients in the study group reported satisfaction, while 31 in the control group expressed satisfaction. The nursing satisfaction rate was significantly higher in the study group than in the control group (P < .05). Conclusions: Quality nursing care during visual electrophysiology examinations proves to be highly effective in enhancing patient compliance, fostering a higher rate of patient cooperation, and mitigating patient stress. Furthermore, it contributes to the improvement of patient satisfaction with nursing care, ultimately elevating the overall healthcare relationship.

Integrative analysis of microbiota and metabolomics in chromium-exposed silkworm (Bombyx mori) midguts based on 16S rDNA sequencing and LC/MS metabolomics.

The gut microbiota, a complex ecosystem integral to host wellbeing, is modulated by environmental triggers, including exposure to heavy metals such as chromium. This study aims to comprehensively explore chromium-induced gut microbiota and metabolomic shifts in the quintessential lepidopteran model organism, the silkworm (Bombyx mori). The research deployed 16S rDNA sequence analysis and LC/MS metabolomics in its experimental design, encompassing a control group alongside low (12 g/kg) and high (24 g/kg) feeding chromium dosing regimens. Considerable heterogeneity in microbial diversity resulted between groups. Weissella emerged as potentially resilient to chromium stress, while elevated Propionibacterium was noted in the high chromium treatment group. Differential analysis tools LEfSe and random forest estimation identified key species like like Cupriavidus and unspecified Myxococcales, offering potential avenues for bioremediation. An examination of gut functionality revealed alterations in the KEGG pathways correlated with biosynthesis and degradation, suggesting an adaptive metabolic response to chromium-mediated stress. Further results indicated consequential fallout in the context of metabolomic alterations. These included an uptick in histidine and dihydropyrimidine levels under moderate-dose exposure and a surge of gentisic acid with high-dose chromium exposure. These are critical players in diverse biological processes ranging from energy metabolism and stress response to immune regulation and antioxidative mechanisms. Correlative analyses between bacterial abundance and metabolites mapped noteworthy relationships between marker bacterial species, such as Weissella and Pelomonas, and specific metabolites, emphasizing their roles in enzyme regulation, synaptic processes, and lipid metabolism. Probiotic bacteria showed robust correlations with metabolites implicated in stress response, lipid metabolism, and antioxidant processes. Our study reaffirms the intricate ties between gut microbiota and metabolite profiles and decodes some systemic adaptations under heavy-metal stress. It provides valuable insights into ecological and toxicological aspects of chromium exposure that can potentially influence silkworm resilience.

Anti-Aging of the Nervous System and Related Neurodegenerative Diseases With Chinese Herbal Medicine.

Human beings have always pursued a prolonged lifespan, while the aging of the nervous system is associated with a large variety of diseases. Pathological aging of the nervous system results in a series of neurodegenerative diseases and can cause disability and death in the elderly. Therefore, there is an urgent need for the prevention and treatment of nervous system aging. Chinese herbal medicines have a long history, featuring rich and safe ingredients, and have great potential for the development of anti-aging treatment. We searched the publications on PubMed with key words "anti-aging of the nervous system" and "Chinese herbal medicine" in recent 10 years, and found sixteen Chinese herbal medicines. Then by comparing their popularity of use as well as active components based on the research articles, five common Chinese herbal medicines namely Ginseng Radix, Lycii Fructus, Astragali Radix, Coptidis Rhizoma and Ginkgo Folium, were confirmed to be the most related to anti-nervous system aging and neural degenerative diseases. At the same time, the active ingredients, research models, action mechanisms and curative effects of these five common Chinese herbal medicines were reviewed. From the five common Chinese herbal medicines reviewed in this paper, many encouraging effects of Chinese herbal medicines on treating nervous system aging and related diseases were revealed and more potent herbs would be explored with the help of the proposed possible mechanisms.

Pharmacological mechanisms of sinomenine in anti-inflammatory immunity and osteoprotection in rheumatoid arthritis: A systematic review.

BACKGROUND: Sinomenine (SIN) is the main pharmacologically active component of Sinomenii Caulis and protects against rheumatoid arthritis (RA). In recent years, many studies have been conducted to elucidate the pharmacological mechanisms of SIN in the treatment of RA. However, the molecular mechanism of SIN in RA has not been fully elucidated. PURPOSE: To summarize the pharmacological effects and molecular mechanisms of SIN in RA and clarify the most valuable regulatory mechanisms of SIN to provide clues and a basis for basic research and clinical applications. METHODS: We systematically searched SciFinder, Web of Science, PubMed, China National Knowledge Internet (CNKI), the Wanfang Databases, and the Chinese Scientific Journal Database (VIP). We organized our work based on the PRISMA statement and selected studies for review based on predefined selection criteria. OUTCOME: After screening, we identified 201 relevant studies, including 88 clinical trials and 113 in vivo and in vitro studies on molecular mechanisms. Among these studies, we selected key results for reporting and analysis. CONCLUSIONS: We found that most of the known pharmacological mechanisms of SIN are indirect effects on certain signaling pathways or proteins. SIN was manifested to reduce the release of inflammatory cytokines such as Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and IL-1ß, thereby reducing the inflammatory response, and apparently blocking the destruction of bone and cartilage. The regulatory effects on inflammation and bone destruction make SIN a promising drug to treat RA. More notably, we believe that the modulation of α7nAChR and the regulation of methylation levels at specific GCG sites in the mPGES-1 promoter by SIN, and its mechanism of directly targeting GBP5, certainly enriches the possibilities and the underlying rationale for SIN in the treatment of inflammatory immune-related diseases.

Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway.

OBJECTIVE: This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats. METHODS: The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA. RESULTS: APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05). CONCLUSION: EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.

Dietary trace mineral pattern influences gut microbiota and intestinal health of broilers.

Dietary trace minerals can impact gut flora, which can further affect intestinal health. However, the dietary balance pattern of trace minerals for the intestinal health of broilers needs to be explored. The present study was conducted to investigate the effect of the dietary pattern of Cu, Fe, Mn, Zn, and Se on the intestinal morphology, microbiota, short-chain fatty acid concentrations, antioxidant status, and the expression of tight junction proteins in broilers. A total of 240 1-d-old Arbor Acres male broilers were randomly assigned to one of five treatments with six replicate cages of eight birds per cage for each treatment. The birds were fed the corn-soybean meal basal diet supplemented with five combination patterns of trace minerals for 42 d. The dietary treatments were as follows: the inorganic sources were added to the diet based on the recommendations of the current National Research Council (NRC, T1) and Ministry of Agriculture of P.R. China (MAP) (T2) for broiler chicks, respectively; the inorganic sources were added to the diet at the levels based on our previous results of inorganic trace mineral requirements for broilers (T3); the organic sources were added to the diet at the levels considering the bioavailabilities of organic trace minerals for broilers described in our previous studies (T4); and the organic sources were added to the diet based on the recommendations of the current MAP for broiler chicks (T5). The results showed that broilers from T1 had lower (P < 0.05) crypt depth (CD), and a higher (P < 0.05) villus height: CD in duodenum on day 21 and lower CD (P < 0.05) in jejunum on day 42 than those from T3 and T4. Broilers from T1, T3, and T5 had a higher (P < 0.05) Shannon index in cecum on day 21 than those from T4. Broilers from T1 had a higher (P < 0.05) abundance of Lactobacillus in ileum on day 21 than those from T2 and T3. Broilers from T1, T2, and T5 had a higher (P < 0.05) valeric acid concentrations in cecum on day 42 than those from T3 and T4. In addition, Birds from T2 had higher (P < 0.05) Claudin-1 mRNA levels in jejunum on day 42 than those from T3 and T4. And birds from T3, T4, and T5 had a higher (P < 0.05) Occludin protein expression levels in duodenum on day 42 than those from T2. These results indicate that dietary pattern of Cu, Fe, Mn, Zn, and Se influenced gut flora and intestinal health of broilers, and the appropriate pattern of Cu, Fe, Mn, Zn, and Se in the diet for intestinal health of broilers would be Cu 12 mg, Fe 229 mg, Mn 81 mg, Zn 78 mg, and Se 0.24 mg/kg (1 to 21 d of age), and Cu 11 mg, Fe 193 mg, Mn 80 mg, Zn 73 mg, and Se 0.22 mg/kg (22 to 42 d of age), when the trace minerals as inorganic sources were added to diets according to the recommendations of the current NRC.

Information is still scarce regarding the effect of dietary trace mineral patterns on the intestinal health of broilers. The results indicated that dietary trace mineral pattern influenced intestinal health of broilers, and the appropriate pattern of trace minerals in the diet for intestinal health of broilers would be Cu 12 mg, Fe 229 mg, Mn 81 mg, Zn 78 mg, and Se 0.24 mg/kg (1 to 21 d of age), and Cu 11 mg, Fe 193 mg, Mn 80 mg, Zn 73 mg, and Se 0.22 mg/kg (22 to 42 d of age), when the trace minerals as inorganic sources were added to diets according to the recommendations of the current National Research Council. Our results provided scientific experimental bases for improving intestinal health of broilers by nutritional strategy.

Sinomenine ameliorates collagen-induced arthritis in mice by targeting GBP5 and regulating the P2X7 receptor to suppress NLRP3-related signaling pathways.

Sinomenine (SIN) is an isoquinoline alkaloid isolated from Sinomenii Caulis, a traditional Chinese medicine used to treat rheumatoid arthritis (RA). Clinical trials have shown that SIN has comparable efficacy to methotrexate in treating patients with RA but with fewer adverse effects. In this study, we explored the anti-inflammatory effects and therapeutic targets of SIN in LPS-induced RAW264.7 cells and in collagen-induced arthritis (CIA) mice. LPS-induced RAW264.7 cells were pretreated with SIN (160, 320, 640 µM); and CIA mice were administered SIN (25, 50 and 100 mg·kg-1·d-1, i.p.) for 30 days. We first conducted a solvent-induced protein precipitation (SIP) assay in LPS-stimulated RAW264.7 cells and found positive evidence for the direct binding of SIN to guanylate-binding protein 5 (GBP5), which was supported by molecular simulation docking, proteomics, and binding affinity assays (KD = 3.486 µM). More importantly, SIN treatment markedly decreased the expression levels of proteins involved in the GBP5/P2X7R-NLRP3 pathways in both LPS-induced RAW264.7 cells and the paw tissue of CIA mice. Moreover, the levels of IL-1ß, IL-18, IL-6, and TNF-α in both the supernatant of inflammatory cells and the serum of CIA mice were significantly reduced. This study illustrates a novel anti-inflammatory mechanism of SIN; SIN suppresses the activity of NLRP3-related pathways by competitively binding GBP5 and downregulating P2X7R protein expression, which ultimately contributes to the reduction of IL-1ß and IL-18 production. The binding specificity of SIN to GBP5 and its inhibitory effect on GBP5 activity suggest that SIN has great potential as a specific GBP5 antagonist.

Dietary calcium and nonphosphate phosphorus interaction influences tibiotarsus development and related gene expression of broilers from 1 to 21 days of age.

The dietary needs of calcium (Ca) and phosphorus (P) are interdependent, thus accurate evaluation of Ca and P requirements of broilers to support skeleton health and optimal growth is critical. The present study was carried out to investigate the effects of dietary Ca and nonphytate P (NPP) levels and their interactions on growth performance, tibiotarsus characteristics, tibiotarsus metabolism-related enzyme and proteins, and their gene expression of broilers, so as to provide a rational recommendation for Ca and NPP levels in diet. A total of 540 one-day-old Arbor Acres male broilers were randomly allotted to 1 of 15 treatments with 6 replicate cages of 6 birds per cage for each treatment in a completely randomized design involving a 5 × 3 factorial arrangement of treatments (5 levels of Ca × 3 levels of NPP). The birds were fed the corn-soybean meal diet containing 0.60%, 0.70%, 0.80%, 0.90%, or 1.00% Ca and 0.35%, 0.40%, or 0.45% NPP for 21 d. Dietary Ca level affected (P < 0.03) the bone mineral density, bone mineral content (BMC), breaking strength, ash percentage and ash Ca contents in tibia, which showed linear (P < 0.006) responses to dietary Ca levels. Dietary NPP level affected (P < 0.05) tibia BMC, ash percentage, and FGF23 mRNA level. Broilers that received 0.40% and 0.45% NPP had higher (P < 0.04) tibia BMC and ash percentage than those that received 0.35% NPP, but no differences (P > 0.05) were found between 0.40% and 0.45% NPP. Broilers that received 0.40% NPP had higher (P = 0.02) tibia FGF23 mRNA level than those that received 0.35% NPP, but no differences (P > 0.05) were detected between 0.40% and 0.45% NPP or 0.45% and 0.35% NPP. The interactions between dietary Ca and NPP affected (P < 0.05) ADG, ALP activity, bone gal protein, FGF23 contents, and the mRNA expression levels ALP and bone gal protein in tibia of broilers. Results from the present study indicate that dietary Ca and NPP interaction influences growth, tibiotarsus development, and related gene expression of broiler chickens. Considering all the criteria, the dietary levels of 0.90% Ca and 0.45% NPP would be optimal for both growth and tibiotarsus development of broilers fed a conventional corn-soybean meal diet from 1 to 21 d of age.

Manganese alleviates heat stress of primary cultured chick embryonic myocardial cells via enhancing manganese superoxide dismutase expression and attenuating heat shock response.

Manganese (Mn) is an essential trace element that has been shown to attenuate the adverse effects of heat stress in the heart of broiler breeders and embryos. However, the underlying molecular mechanisms involving this process remain unclear. Therefore, two experiments were conducted to investigate the possible protective mechanisms of Mn on primary cultured chick embryonic myocardial cells exposed to heat challenge. In experiment 1, the myocardial cells were exposed to 40 °C (normal temperature, NT) and 44 °C (high temperature, HT) for 1, 2, 4, 6 or 8 h. In experiment 2, the myocardial cells were preincubated with no Mn supplementation (CON), 1 mmol/L of Mn as the inorganic MnCl2 (iMn) or organic Mn proteinate (oMn) under NT for 48 h, and then continuously incubated under NT or HT for another 2 or 4 h. The results from experiment 1 showed that the myocardial cells incubated for 2 or 4 h had the highest (P < 0.0001) heat-shock protein 70 (HSP70) or HSP90 mRNA levels than those incubated for other incubation times under HT. In experiment 2, HT increased (P < 0.05) the heat-shock factor 1 (HSF1) and HSF2 mRNA levels as well as Mn superoxide dismutase (MnSOD) activity of myocardial cells compared with NT. Furthermore, supplemental iMn and oMn increased (P < 0.02) HSF2 mRNA level and MnSOD activity of myocardial cells compared with the CON. Under HT, the HSP70 and HSP90 mRNA levels were lower (P < 0.03) in iMn group than in the CON group, in oMn group than in iMn group; and the MnSOD mRNA and protein levels were higher (P < 0.05) in oMn group than in the CON and iMn groups. These results from the present study indicate that supplemental Mn, especially oMn, could enhance the MnSOD expression and attenuate heat shock response to protect against heat challenge in primary cultured chick embryonic myocardial cells.

Extracellular zinc regulates contextual fear memory formation in male rats through MMP-BDNF-TrkB pathway in dorsal hippocampus and basolateral amygdala.

Large amount of zinc (100 µM even up to 300 µM) is released from the nerve terminals in response to high frequency neuronal stimulation in certain brain regions including hippocampus and amygdala. However, its precise pharmacological effect is poorly understood. Here, we investigated the role of extracellular zinc (endogenous zinc) and exogenous zinc in memory formation using contextual fear conditioning (CFC) model. Male Sprague Dawley rats were trained for fear conditioning followed by in vivo microdialysis for collection of microdialysate samples from CA1 and CA3 regions of hippocampus and basolateral amygdala (BLA). Extracellular zinc chelator CaEDTA, BDNF scavenger TrkB-Fc, exogenous 7,8-DHF and matrix metalloproteinases (MMP) inhibitor were infused into the CA1 and CA3 regions of hippocampus and BLA after CFC. Different doses of exogenous zinc hydroaspartate were administered intraperitoneally immediately after CFC. We found that CFC increased the level of extracellular zinc in the hippocampus and BLA. Infusing the CaEDTA, TrkB-Fc and MMP inhibitor into the CA1 and CA3 regions of hippocampus and BLA disrupted the fear memory formation. Furthermore, administration of TrKB agonist 7,8-DHF reversed the inhibitory effect of CaEDTA on fear memory formation, suggesting that extracellular zinc may regulate fear memory formation via the BDNF-TrKB pathway. We also found that high dose of exogenous zinc hydroaspartate supplementation increased extracellular zinc levels in brain and enhanced fear memory formation. Altogether, these findings indicate that extracellular zinc may participate in formation of contextual fear memory through MMP-BDNF-TrkB pathway in the hippocampus and BLA.

Blunted superior temporal gyrus activity to negative emotional expression after mindfulness-based cognitive therapy for late-life depression.

Facial emotion recognition plays an important role in social functioning. Patients with late-life depression (LLD) often have abnormal facial emotion recognition. Mindfulness-based cognitive therapy (MBCT) is beneficial in treating depression. This study examined whether MBCT can act as an effective augmentation of antidepressants and improve facial emotion recognition in patients with LLD and its underlying neural mechanism. Patients with LLD were randomized into two groups (n = 30 per group). The MBCT group received an eight-week MBCT in conjunction with stable medication treatment. The other group was treated as usual (TAU group) with stable medication treatment. The positive affect (PA) scale, negative affect (NA) scale, and facial emotion recognition task with an fMRI scan were performed before and after the trial. After eight weeks of treatment, the repeated ANOVA showed that the PA score in the MBCT group significantly increased [F (1,54) = 13.31, p = 0.001], but did not change significantly [F (1,54) = 0.58, p = 0.449] in the TAU group. The NA scores decreased significantly in both the MBCT group [F (1,54) = 19.01, p < 0.001] and the TAU group [F (1,54) = 16.16, p < 0.001]. Patients showed an increase in recognition accuracy and speed of angry and sad faces after 8 weeks of MBCT. No improvement was detected in the TAU group after treatment. A significant interaction effect was found in the change of activation of the left superior temporal gyrus (L-STG) to negative emotional expression between time and groups. Furthermore, a decrease in activation of L-STG to negative emotional expression was positively correlated with the increase in PA score. The MBCT is beneficial for improving affect status and facial emotion recognition in patients with LLD, and the L-STG is involved in this process.

Metabolic utilization of intravenously injected iron from different iron sources in target tissues of broiler chickens.

No information is available regarding the utilization of iron (Fe) from different Fe sources at a target tissue level. To detect differences in Fe metabolic utilization among Fe sources, the effect of intravenously injected Fe on growth performance, hematological indices, tissue Fe concentrations and Fe-containing enzyme activities and gene expressions of Fe-containing enzymes or protein in broilers was investigated. On d 22 post-hatching, a total of 432 male chickens were randomly allotted to 1 of 9 treatments in a completely randomized design. Chickens were injected with either a 0.9% (wt/vol) NaCl solution (control) or a 0.9% NaCl solution supplemented with Fe sulphate or 1 of 3 organic Fe sources. The 3 organic Fe sources were Fe chelates with weak (Fe-MetW), moderate (Fe-ProtM) or extremely strong (Fe-ProtES) chelation strength. The 2 Fe dosages were calculated according to the Fe absorbabilities of 10% and 20% every 2 d for a duration of 20 d. Iron injection did not affect (P > 0.05) ADFI, ADG or FCR during either 1 to 10 d or 11 to 20 d after injections. Hematocrit and Fe concentrations in the liver and kidney on d 10 after Fe injections, and Fe concentrations in the liver or pancreas and ferritin heavy-chain (FTH1) protein expression level in the liver or spleen on d 20 after Fe injections increased (P ≤ 0.05) as injected Fe dosages increased. When the injected Fe level was high at 20% Fe absorbability, the chickens injected with Fe-ProtES had lower (P < 0.001) liver or kidney Fe concentrations and spleen FTH1 protein levels than those injected with Fe-MetW or Fe-ProtM on d 20 after injections. And they had lower (P < 0.05) liver cytochrome C oxidase mRNA levels on d 20 after injections than those injected with Fe-MetW or Fe sulphate. The results from this study indicate that intravenously injected Fe from Fe-ProtES was the least utilizable and functioned in the sensitive target tissue less effectively than Fe from Fe sulfate, Fe-MetW or Fe-ProtM.

[A novel phenylisoquinoline alkaloid with cardioprotective effect from Aconiti Lateralis Radix Praeparata].

Macroporous resin chromatography, silica gel column chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography were performed to isolate two compounds from the acid extract of the lateral roots of Aconitum carmichaelii: a new 9-phenylisoquinoline alkaloid(1) and a known pavine alkaloid(2). Their structures were elucidated by spectroscopy. The absolute configuration of compound 1 was identified by electronic circular dichroism(ECD) and it was determined to be(aS)-7,8-dimethoxy-9-(2-carboxy-4,5-dimethoxyphenyl)-3,4-dihydroisoquinoline-1(2H)-one(1). The cardioprotective effects of 1 and 2 against doxorubicin-induced toxicity in H9 c2 cells were evaluated. Both of the isoquinoline alkaloids showed cardioprotective activity.

Research Note: Metabolic utilization of iron from different iron sources in primary cultured hepatocytes of broiler embryos.

The present study was carried out to evaluate the effects of iron (Fe) sources and levels on the Fe concentration and expressions of iron-containing enzymes or protein in primary cultured hepatocytes of broiler embryos. The hepatocytes were incubated with 0, 0.25 and 0.50 mmol/L added Fe from either Fe sulfate, or 1 of 3 organic Fe chelates with weak (Fe-Met W), moderate (Fe-Pro M), or extremely strong (Fe-Pro ES) chelation strengths for 24 h. The results showed that all supplemental Fe treatments had higher (P < 0.05) Fe concentration, succinate dehydrogenase (SDH), CAT and ferritin heavy chain 1 (FTH1) mRNA levels than those in the control group. The hepatocytes incubated with Fe-Prot ES had lower (P < 0.009) Fe concentration than those incubated with Fe sulfate, Fe-Met W or Fe-Prot M. The SDH mRNA level was lower (P < 0.05) in Fe sulfate and Fe-Prot ES groups than in Fe-Prot M group. In conclusion, the Fe from Fe-Prot ES was less utilizable than Fe from Fe sulfate, Fe-Met W or Fe-Pro M in primary cultured hepatocytes of broiler embryos.

Evaluation of optimal dietary calcium level by bone characteristics and calcium metabolism-related gene expression of broilers from 22 to 42 d of age.

The current dietary Ca recommendation of broilers is primarily based on the previous studies carried out more than 30 yr ago. However, the modern commercial broilers are quite different from those more than 30 yr ago. The present experiment was conducted to evaluate an optimal dietary Ca level by bone characteristics and Ca metabolism-related gene expression of broilers fed a corn-soybean meal diet from 22 to 42 d of age. A total of 252 22-d-old Arbor Acres male broilers were randomly assigned to 1 of 7 treatments with 6 replicate cages of 6 birds per cage for each treatment. Broilers were fed the corn-soybean meal diets containing 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.00%, or 1.10% Ca for 21 d, and each diet contained 0.31% non-phytate P. The results showed that the mineral contents in tibia and middle toe bone, mineral density in tibia and middle toe bone, middle toe ash percentage, middle toe ash Ca percentage, and tibia alkaline phosphatase mRNA expression level of broilers were influenced (P < 0.04) by dietary Ca level and increased quadratically (P < 0.05) as dietary Ca level increased. The estimates of optimal dietary Ca levels were 0.55%, 0.60%, 0.70%, 0.72%, 0.63%, 0.66%, and 0.70%, respectively, based on the best fitted broken-line, quadratic, or asymptotic models (P < 0.02) of the above sensitive indices. These results indicate that the optimal dietary Ca level would be 0.72% to support all of the Ca metabolism and bone development of broilers fed the corn-soybean meal diet from 22 to 42 d of age.

The present experiment was conducted to evaluate an optimal dietary Ca level by bone characteristics and Ca metabolism-related gene expression of broilers fed a corn-soybean meal diet from 22 to 42 d of age. A total of 252 22-d-old Arbor Acres male broilers were randomly assigned to 1 of 7 treatments with 6 replicate cages of 6 birds per cage for each treatment. Broilers were fed the corn-soybean meal diets containing 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.00%, or 1.10% Ca for 21 d, and each diet contained 0.31% non-phytate P. The results showed that the tibia and middle toe bone mineral contents, tibia and middle toe bone mineral density, middle toe ash percentage, middle toe ash Ca percentage, and tibia alkaline phosphatase mRNA expression level were sensitive criteria to estimate the optimal dietary Ca levels of broilers. The estimates of optimal dietary Ca levels were 0.55% to 0.72% based on the above sensitive criteria. These results indicate that the optimal dietary Ca level would be 0.72% to support all of the Ca metabolism and bone development of broilers fed the corn-soybean meal diet from 22 to 42 d of age.

Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce.

OBJECTIVES: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. METHODS: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. RESULTS: Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support (recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/-), folic acid (-), vitamin C (-), tryptophan (+/-), creatine (+/-), inositol (-), magnesium (-), and n-acetyl cysteine (NAC) (+/-) and SAMe (+/-) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/-). NAC was weakly recommended (+) in the treatment of OCD-related disorders; however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/-) and omega-9 fatty acids (-), acetyl L carnitine (-), and zinc (+/-) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John's wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (-) and chamomile (+/-) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/-). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy. CONCLUSIONS: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Mindfulness-Based Cognitive Therapy Regulates Brain Connectivity in Patients With Late-Life Depression.

Late-life depression (LLD) is an important public health problem among the aging population. Recent studies found that mindfulness-based cognitive therapy (MBCT) can effectively alleviate depressive symptoms in major depressive disorder. The present study explored the clinical effect and potential neuroimaging mechanism of MBCT in the treatment of LLD. We enrolled 60 participants with LLD in an 8-week, randomized, controlled trial (ChiCTR1800017725). Patients were randomized to the treatment-as-usual (TAU) group or a MBCT+TAU group. The Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to evaluate symptoms. Magnetic resonance imaging (MRI) was used to measure changes in resting-state functional connectivity and structural connectivity. We also measured the relationship between changes in brain connectivity and improvements in clinical symptoms. HAMD total scores in the MBCT+TAU group were significantly lower than in the TAU group after 8 weeks of treatment (p < 0.001) and at the end of the 3-month follow-up (p < 0.001). The increase in functional connections between the amygdala and middle frontal gyrus (MFG) correlated with decreases in HAMA and HAMD scores in the MBCT+TAU group. Diffusion tensor imaging analyses showed that fractional anisotropy of the MFG-amygdala significantly increased in the MBCT+TAU group after 8-week treatment compared with the TAU group. Our study suggested that MBCT improves depression and anxiety symptoms that are associated with LLD. MBCT strengthened functional and structural connections between the amygdala and MFG, and this increase in communication correlated with improvements in clinical symptoms. Randomized Controlled Trial; Follow-Up Study; fMRI; Brain Connectivity.